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Author: Dhanashri Karry   Abstract This analysis explores the critical role of resource allocation in addressing disparities and fostering balanced development between urban centres and rural regions in India, focusing on Mumbai and Bihar. Mumbai, a major urban hub, benefits from substantial investments in healthcare, education, and infrastructure, while Bihar, a predominantly rural state, struggles with inadequate facilities and limited access to basic services. Key findings reveal significant disparities in healthcare access, education quality, and infrastructure development. The study highlights the need for targeted policies and strategic investments to address the unique challenges of both urban and rural areas, aiming to improve living conditions, healthcare access, and socio-economic opportunities for all residents. By focusing on sustainable development and inclusive policies, it is possible to enhance the quality of life and ensure equitable resource distribution across India. Biography Dhanashri Karry is a 10th grader who attends Woodbridge Academy Magnet School. She is deeply interested in the topic of resource allocation disparities between Mumbai and Bihar, two regions in the country of India. This is because medical ethics itself is one of Dhanashri’s keen interests and the contrast between resource allocation between rural and urban areas fueled her determination to explore and address these inequities. In her free time, she likes to run long distances, hike, and practice singing Carnatic music.     Introduction Resource partitioning, or the distribution of resources among various regions and populations, is crucial for balanced development and addressing disparities. The stark contrast between urban centres like Mumbai and rural regions like Bihar in India shows the challenges and complexities involved in resource allocation. Examining how resources are distributed and utilised in these areas provides valuable insights into broader socio-economic dynamics and persistent inequalities that affect millions [1] . In this analysis, we will delve into the various aspects of resource allocation in Mumbai and Bihar, exploring their impacts on healthcare, education, infrastructure, and overall quality of life.   Daily Life Struggles In Mumbai, daily life struggles are particularly acute in slum areas. The high cost of living forces many to reside in slums with poor living conditions, lacking basic amenities like clean water, sanitation, and electricity [2]. Pollution, including air and water quality, is a major concern, and rapid urbanisation has led to environmental degradation, affecting the quality of life. Residents  of slums face major obstacles to accessing basic services and amenities [3] . Women, especially in lower socioeconomic groups, face significant barriers in accessing education, healthcare, and employment opportunities. Gender-based violence and discrimination further exacerbate these challenges [4] . The high population density and rapid urbanisation have led to strain on infrastructure and resources, resulting in poor living conditions for many residents [4]. The disparity in living conditions between affluent areas and slums underscores the need for targeted policies and investments to address the unmet needs of the urban poor [5] . In Bihar, daily life struggles are primarily in rural areas, where inadequate infrastructure and services pose challenges to daily life. Traditional practices and social norms restrict women's access to education, healthcare, and employment. Gender-based violence is also a significant issue [6]. High poverty levels limit access to basic necessities like food, clean water, and healthcare. Many families struggle to afford even primary education for their children. Poor infrastructure and limited transportation options further restrict mobility and access to markets and services, which shows the need for targeted policies and investments to address these challenges [7].   Importance of Resource Allocation in Urban and Rural Areas Effective resource allocation is essential for sustainable development. Urban areas rely on it to support infrastructure, healthcare, education, and economic growth. Conversely, rural areas need resources to enhance agricultural productivity, healthcare, education, and connectivity. Disparities in resource allocation between urban and rural regions can lead to unequal growth, perpetuating poverty and limiting opportunities [8]. In urban centres like Mumbai, the focus is on maintaining and improving the complex infrastructure that supports its large population and economic activities. This includes investing in advanced healthcare facilities, efficient public transportation systems, and high-quality educational institutions [9]. The availability of these resources attracts businesses and skilled workers, driving further economic growth. However, the challenges of rapid urbanisation, such as traffic congestion, pollution, and housing shortages, necessitate continuous investment and planning [9]. In contrast, rural areas like Bihar face different challenges that require tailored resource allocation strategies. The primary focus in these areas is on improving agricultural productivity, ensuring access to basic healthcare and education, and developing infrastructure such as roads and electricity supply. The lack of investment in these critical areas can result in poor living standards, limited economic opportunities, and a cycle of poverty [10]. Effective resource allocation in rural areas is essential to improve the quality of life and create opportunities for sustainable development.   Overview of Population, Geographical, Social, Economic, and Traditional Aspects Mumbai, with a population exceeding 20 million, is one of the most densely populated cities globally [11 ;   12] . Located on India's west coast, it is a major port city with a coastal landscape. Mumbai is a melting pot of cultures, languages, and religions, hosting diverse communities from across India. Known as India's financial capital, it houses the Bombay Stock Exchange and numerous multinational corporations [13]. Its economy is driven by finance, entertainment, textiles, and commerce. Despite its modern outlook, Mumbai retains a rich cultural heritage with festivals, traditional markets, and historic landmarks. Mumbai’s population density is approximately 20,634 people per square kilometre, leading to significant strain on infrastructure and resources [12]. The city’s economy, driven by sectors such as finance, media, and entertainment, contributes substantially to India’s GDP [14]. The presence of major financial institutions, corporate headquarters, and the Bollywood film industry makes Mumbai a hub of economic activity. However, this economic prosperity coexists with stark disparities, as evidenced by the large slum populations living in areas like Dharavi, where living conditions are harsh and access to basic amenities is limited [15]. In contrast, Bihar has a population of over 100 million, with a lower population density compared to Mumbai, though still high by rural standards [16]. Situated in eastern India, Bihar is landlocked with a predominantly agrarian landscape, characterised by the fertile plains of the Ganges River. The state is socially diverse, with various caste groups and communities. Social stratification and traditional practices remain influential. Bihar’s economy is primarily agricultural, with rice, wheat, and maize as the main crops [17]. Industrialization is minimal, and the state has one of the lowest per capita incomes in India. Bihar also boasts a rich historical and cultural heritage, being home to ancient universities like Nalanda and significant religious sites [18]. Bihar’s population density is around 1,106 people per square kilometre, significantly lower than Mumbai but still dense for a largely rural state [19]. The state’s reliance on agriculture, which employs a significant portion of the population, points out the need for effective resource allocation to improve agricultural productivity and infrastructure [17]. The historical significance of sites like Nalanda University and Bodh Gaya adds a cultural dimension to Bihar’s identity, yet the state faces challenges in translating this heritage into economic growth and development.   Medical Access Both Mumbai and Bihar face many healthcare challenges due to the inadequate healthcare infrastructure and shortage of doctors and hospital beds. Mumbai boasts a higher number of doctors and hospital beds per capita compared to Bihar. The city has approximately 7 doctors per 1,000 people and around 1.3 hospital beds per 1,000 people [20 ; 21; 22]. Mumbai's healthcare infrastructure includes several renowned public hospitals such as KEM Hospital, Sion Hospital, and JJ Hospital, as well as numerous private hospitals and clinics offering specialised care. This extensive network of healthcare facilities provides a wide range of medical services, from primary care to advanced tertiary care [23]. Bihar, on the other hand, faces a severe shortage of healthcare professionals and facilities. The state has about 1 doctor for every 17,685 people and the number of hospital beds per 1,000 people is one of the lowest ratios in India [24 ; 25 ; 26]. This shortage is particularly acute in rural areas, where primary health centres are often understaffed and lack basic medical equipment. The limited availability of healthcare professionals and facilities significantly impacts the quality of care available to the population, leading to poor health outcomes and high mortality rates [27 ; 28 ; 29].   Resource comparisons Allocation of Resources in Mumbai Mumbai benefits from substantial resource allocation due to its economic importance. The healthcare system includes numerous public and private hospitals, specialised medical institutions, and healthcare facilities [30]. Despite this, high population density results in overcrowded hospitals and long waiting times. Significant investments in transportation include an extensive railway network, roads, and public transportation systems like buses and the metro. However, traffic congestion and pollution remain major issues [31]. Mumbai offers a wide range of educational institutions from primary schools to prestigious universities and technical institutes, attracting students from across India and abroad. Real estate in Mumbai is among the most expensive globally, with stark contrasts in living conditions, such as in slum areas like Dharavi, where many lack basic amenities [30 ; 32]. Mumbai’s healthcare infrastructure comprises both public and private sectors. The city hosts premier institutions like Tata Memorial Hospital and Sir J.J. Hospital, providing advanced medical care and attracting patients from across the country [30]. However, the demand for healthcare services far exceeds supply, leading to overcrowded facilities and long waiting times. Public healthcare centres often struggle with inadequate funding and resources, affecting the quality of care provided to the urban poor [30]. Transportation in Mumbai is characterised by an extensive suburban railway network, which is the lifeline of the city. The Mumbai Metro and Monorail projects aim to ease the burden on the railway system and reduce traffic congestion. Despite these efforts, traffic congestion remains a significant issue due to the high number of vehicles and inadequate road infrastructure [30 ; 33]. The city’s real estate market is among the most expensive globally, driven by high demand and limited space. This results in significant disparities in living conditions, with affluent areas boasting luxury apartments and slum areas facing overcrowded and unsanitary conditions [34]. Education in Mumbai is a mixed bag. The city is home to some of India’s most prestigious educational institutions, such as the Indian Institute of Technology (IIT) Bombay and the University of Mumbai [35]. These institutions attract students from all over India and even abroad. However, there is also a significant disparity in the quality of education between private and public schools. Many public schools, especially those in slum areas, lack basic facilities and struggle with inadequate teaching staff and resources [36].   Allocation of Resources in Bihar Bihar’s resource allocation reflects its agrarian economy and developmental challenges. The state struggles with inadequate healthcare infrastructure, a shortage of medical professionals, and poorly equipped facilities, particularly in rural areas. While there have been improvements in road connectivity and electricity supply, overall infrastructure development lags behind more urbanised states. Rural areas often lack basic amenities like clean drinking water and sanitation. Despite progress in literacy rates, the quality of education remains a concern, with many schools lacking proper facilities and qualified teachers. Significant resources are allocated to agriculture, with schemes aimed at improving productivity and farmer welfare. However, frequent floods and droughts pose ongoing challenges [37]. The healthcare system in Bihar is characterised by a severe shortage of healthcare professionals and facilities. Rural areas rely heavily on primary health centres, which often lack the necessary equipment and staff to provide adequate care. The state faces a high burden of communicable diseases, maternal and child health issues, and malnutrition. The lack of healthcare infrastructure and medical personnel results in poor health outcomes and a high mortality rate [38]. Infrastructure development in Bihar has seen some progress, with improvements in road connectivity and electrification. However, many rural areas still lack basic amenities such as clean drinking water, sanitation, and a reliable electricity supply. The state’s education system faces significant challenges, with many schools lacking proper facilities and qualified teachers. Efforts to improve literacy rates have yielded some success, but the quality of education remains a concern, particularly in rural areas [39]. Agriculture is the backbone of Bihar’s economy, employing a significant portion of the population [37]. The state allocates substantial resources to agricultural development, with schemes aimed at improving productivity, irrigation, and farmer welfare. However, frequent natural disasters such as floods and droughts pose ongoing challenges, affecting agricultural output and livelihoods. The state’s economy remains largely agrarian, with limited industrialization and job opportunities, contributing to widespread poverty and underdevelopment [38].   Comparison of Healthcare Resource Allocation: Mumbai vs. Bihar In Mumbai, healthcare facilities are more advanced and numerous, featuring specialised hospitals, a higher number of healthcare professionals, and better medical technology [40]. However, the high population density leads to overcrowded facilities and unequal access to quality care, particularly for the poor [40]. In contrast, Bihar's healthcare system is severely under-resourced, with rural areas often relying on primary health centres that lack adequate equipment and staff [2]. The state faces a high burden of communicable diseases and maternal and child health issues. The lack of infrastructure and medical personnel results in poor healthcare outcomes compared to urban areas like Mumbai [2]. Mumbai’s healthcare system benefits from significant investment and advanced medical technology. The city hosts renowned institutions like Tata Memorial Hospital, known for its cancer treatment, and the Haffkine Institute, specialising in biomedical research. Private hospitals like Lilavati Hospital and Hinduja Hospital offer world-class medical care, attracting patients from across India and abroad. However, the public healthcare system faces significant challenges, with overcrowded hospitals and long waiting times [41]. The high cost of private healthcare services also limits access for low-income populations, leading to disparities in healthcare access and outcomes [42]. In contrast, Bihar’s healthcare system is characterised by a severe shortage of medical professionals and facilities. The state has one of the lowest doctor-to-patient ratios in India, with many rural areas relying on under-resourced primary health centres [24 ; 25]. The lack of infrastructure and medical personnel results in poor healthcare outcomes, with high rates of maternal and child mortality and a significant burden of communicable diseases [43 ; 44]. Efforts to improve healthcare infrastructure have been hampered by inadequate funding and logistical challenges, further exacerbating the disparities between urban and rural healthcare access.   State of Public Health Mumbai, with its diverse and dense population, faces unique public health challenges. The city's healthcare system is a blend of public and private sectors, offering a wide range of medical services. Public health initiatives in Mumbai have focused on combating infectious diseases, improving maternal and child health, and addressing lifestyle-related illnesses such as diabetes and cardiovascular diseases [45]. Despite these efforts, the high population density and rapid urbanisation have led to overcrowded healthcare facilities and uneven access to services. In Bihar, public health challenges are primarily driven by inadequate infrastructure, limited resources, and high poverty levels. The state's public health system is underfunded and understaffed, struggling to meet the basic healthcare needs of its population [46]. Bihar has a high prevalence of communicable diseases such as tuberculosis, malaria, and diarrhoea, which are exacerbated by poor sanitation and lack of clean drinking water. Maternal and child health indicators are also poor, with high rates of maternal and infant mortality [47 ; 48]. Demographics and Mortality Rates Mumbai's population of over 20 million includes a mix of age groups, socioeconomic statuses, and cultural backgrounds. The city has a relatively lower infant mortality rate (IMR) compared to the national average, thanks to better access to maternal and child healthcare services [49]. However, significant disparities exist, with slum areas experiencing higher mortality rates due to poor living conditions, malnutrition, and limited access to healthcare [49]. The life expectancy in Mumbai is relatively high, reflecting better healthcare access and living conditions for a substantial portion of the population [49]. In contrast, Bihar's population of over 100 million is predominantly young, with a significant proportion under the age of 15. The state's IMR is higher than the national average, reflecting substantial challenges in maternal and child healthcare [50]. Factors contributing to high mortality rates in Bihar include inadequate healthcare infrastructure, poor nutrition, high rates of infectious diseases, and lack of access to clean water and sanitation [50 ; 51 ; 52]. The state's life expectancy is lower compared to urban areas like Mumbai, indicating significant health disparities and poor living conditions [52]. Aging Demographics Mumbai's demographic profile includes a growing ageing population, necessitating increased healthcare resources and services for the elderly. The city has several specialised geriatric care centres and facilities catering to the needs of senior citizens [53]. However, the high cost of private healthcare services and limited availability of affordable public healthcare options pose challenges for low-income elderly residents. The demand for geriatric care is expected to rise as the population ages, highlighting the need for targeted healthcare policies and investments. In Bihar, the demographic profile is predominantly young, with a smaller proportion of elderly individuals compared to Mumbai. However, the state's healthcare infrastructure is ill-equipped to address the specific needs of the ageing population. There are limited geriatric care facilities, and the overall healthcare system struggles to provide adequate care for the elderly, who often face neglect and inadequate medical attention [54]. The focus of healthcare services in Bihar is primarily on maternal and child health, communicable diseases, and basic healthcare needs, leaving the ageing population underserved [55 ; 56]. Health Care Public vs. Private Healthcare Sectors Mumbai's healthcare system is characterised by a robust mix of public and private sectors. The public sector includes large hospitals such as KEM Hospital, Sion Hospital, and JJ Hospital, which provide affordable care to the city's low-income population [57]. Despite these facilities, the public sector is often overwhelmed by the high patient load, leading to overcrowded conditions and long waiting times. Public hospitals in Mumbai play a critical role in providing healthcare services to the city's vulnerable populations, including the residents of the slums and low-income groups [57]. The private sector in Mumbai is well-developed, with numerous hospitals and clinics offering advanced medical services and state-of-the-art technology. Hospitals like Lilavati, Hinduja, and Breach Candy provide high-quality care but are expensive, limiting access to affluent segments of the population [58]. The disparity between public and private healthcare services calls attention to the unequal access to quality healthcare in the city [58]. While the private sector offers advanced medical treatments and better patient amenities, it remains inaccessible to the majority of the population due to high costs. Bihar's healthcare system is predominantly public, with limited private sector presence. The public sector struggles with inadequate funding, poor infrastructure, and a severe shortage of medical professionals. Primary health centres and district hospitals are the backbone of the state's healthcare system but often lack basic facilities and equipment [58]. The private sector is underdeveloped, with few private hospitals and clinics concentrated mainly in urban areas. This imbalance results in limited access to quality healthcare for the majority of Bihar's population, particularly in rural regions. Efforts to improve healthcare in Bihar often focus on strengthening the public healthcare system, but progress is slow due to systemic challenges and limited resources [59 ; 46 ; 43]. Healthcare Financing and Expenditure Healthcare financing and expenditure in Mumbai and Bihar reflect the broader economic disparities between the two regions. Mumbai, being a wealthy urban centre, benefits from higher public and private healthcare spending. The Maharashtra state government allocates a significant portion of its budget to healthcare, supporting public hospitals and healthcare programs. Additionally, the city's affluent population and corporate presence contribute to substantial private healthcare spending, enabling investments in advanced medical facilities and technologies [60]. Bihar, on the other hand, allocates a smaller portion of its budget to healthcare, reflecting the state's economic constraints and developmental challenges. The state's per capita healthcare expenditure is one of the lowest in India, resulting in underfunded public healthcare facilities and limited resources for healthcare programs. The central government's health schemes and funding provide some support, but the overall financing remains inadequate to meet the healthcare needs of the population [61]. In Mumbai, the combined public and private healthcare expenditure is significantly higher compared to Bihar. The city's advanced medical facilities, specialised hospitals, and availability of high-quality care reflect the substantial investments in healthcare. In contrast, Bihar's healthcare system struggles with limited funding, poor infrastructure, and inadequate resources, leading to significant disparities in healthcare access and outcomes between the two regions [60]. Unmet  Health Care Needs in Both Regions Both Mumbai and Bihar face significant unmet healthcare needs, albeit in different contexts. In Mumbai, despite the availability of advanced healthcare facilities, the high patient load leads to long waiting times and inadequate care for many [26]. People residing in slums and low-income groups face barriers to accessing quality healthcare due to overcrowded public hospitals and high costs of private healthcare. In Bihar, the lack of healthcare infrastructure and professionals results in poor health outcomes. Many rural residents travel long distances to access medical care, which is often unaffordable. The quality of education remains poor, with many schools lacking basic facilities. Higher education opportunities are limited, contributing to low literacy and skill levels [38]. Basic infrastructure such as roads, electricity, and sanitation are inadequate in many areas. Frequent natural disasters exacerbate these challenges, disrupting daily life and economic activities [37]. Healthcare Policy and Strategic Initiatives To address the healthcare disparities between Mumbai and Bihar, it is crucial to implement targeted policies and strategic initiatives. In Mumbai, the focus should be on expanding public healthcare infrastructure, improving the quality of care in public hospitals, and ensuring affordable access to healthcare for all residents. Initiatives to reduce overcrowding in public hospitals, enhance primary healthcare services, and address environmental health concerns such as pollution are essential. Additionally, efforts to improve living conditions in slum areas, including access to clean water, sanitation, and affordable housing, are critical to addressing the broader determinants of health [62 ; 63]. In Bihar, targeted investments in healthcare infrastructure, medical training, and resource allocation are essential to improve healthcare access and outcomes. Strengthening primary healthcare services, expanding the availability of medical professionals in rural areas, and enhancing the quality of care in public hospitals are critical steps. Additionally, addressing the social determinants of health, such as poverty, education, and sanitation, is essential to improving overall health outcomes in the state. Strategic initiatives to enhance maternal and child health services, combat communicable diseases, and improve nutrition and sanitation are vital to addressing the state's healthcare challenges [63 ; 64 ; 65]. Conclusion The contrast between Mumbai and Bihar in terms of healthcare resource allocation represents the diverse challenges faced by urban and rural India. Mumbai's advanced healthcare infrastructure, higher number of medical professionals, and substantial investments in both public and private sectors provide better healthcare access and outcomes for its population [66]. However, disparities exist, particularly in slum areas where access to quality healthcare remains limited. Bihar, with its predominantly rural population, faces severe challenges in healthcare resource allocation. The state's inadequate healthcare infrastructure, shortage of medical professionals, and limited funding result in poor health outcomes and significant disparities in access to care [43]. Addressing these disparities requires targeted policies and investments that consider the unique needs and contexts of both regions. Efforts to improve healthcare in Mumbai should focus on enhancing public healthcare facilities, addressing overcrowding, and ensuring affordable access to quality care for all residents [67]. In Bihar, targeted investments in healthcare infrastructure, medical training, and resource allocation are essential to improve healthcare access and outcomes [68]. Additionally, strengthening public health programs, improving sanitation, and addressing malnutrition are critical to addressing the state's health challenges. Overall, bridging the healthcare resource gap between Mumbai and Bihar is essential for fostering balanced and inclusive development across India. 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Author: Avighna Daruka

Author: Venus Burtea

Author: Daniel Seo

Author: Rithika Jamisetty

Author: Pooja Karthikeyan Introduction Since their emergence, AI technologies, particularly ChatGPT, have become commonplace in all aspects of our lives. Because of its incredible performance capabilities, this data-driven generative AI tool has been employed in various industries, including education, the workplace, entertainment, and others. However, it has limits. Because ChatGPT is trained on vast and publicly available data sets, it may be prone to stereotypes, factual errors, bias, or disinformation [12]. Bias in ChatGPT has been a challenge, particularly in highlighting or maintaining gender bias. Occupational gender bias has long existed in our society, with certain jobs stereotypically assigned to women and men. For example, stereotypically, female jobs include baby sisters, nurses, and receptionists, whereas male jobs include construction workers, electricians, and firefighters. Since ChatGPT and other AI tools are used to generate books, stories, and other content, these tools are in a unique position to influence gender discrimination that is already plaguing our society. Such perpetuation of gender bias can be disruptive and detrimental to our society [5]. Furthermore, occupational stereotypes can considerably influence children's capacity to make professional decisions. Children begin to believe in gender stereotypes at an early age. For example, research indicated that girls in third grade ranked themselves lower than boys in mathematics, even though their test results were identical [10]. As a result, it is critical to understand how consistently ChatGPT promotes gender stereotypes. ChatGPT has been repeatedly proven to reinforce or amplify gender stereotypes [3] [6] [8]. In their study of gender bias and stereotypes in large language models, Kotek et al. discovered that LLMs made biassed assumptions about men's and women's vocations, portraying doctors as males and nurses as women. Such gender bias was also evident in the recommendation letters generated by ChatGPT [6], which highlighted males in leadership positions and females in supportive roles. Even though there is a wide consensus towards the presence of gender bias in ChatGPT, there have been mixed findings on the degree of bias towards stereotypically male or female-dominated jobs. Spillner (2024) investigated gender prejudice in short stories generated by ChatGPT and discovered that the stereotypes about professions generated by ChatGPT outperformed the human occupational gender bias. Furthermore, they found substantial disparities in how gender preconceptions were enhanced for typically male and female occupations, particularly amplifying existing prejudices in female-dominated jobs. On the other hand, Babaei et al. (2024) explored gender bias by directly prompting names for female or male-dominated professions for a play. Even when the prompt was repeated many times, they found that the ChatGPT responses were gender-balanced and politically correct for the occupations they tested. One of the reasons for these mixed results may be due to the variability and reduced consistency associated with large language models like ChatGPT. Since the influence of ChatGPT in specific and generative AI, in general, is increasing exponentially, it is important to have an unambiguous understanding of their role in the perpetuation of gender bias. ChatGPT-3.5, the free version, is frequently shown to generate larger and less concise prompt responses [7]. Systematic studies on the consistency and uniformity of ChatGPT responses have shown that the outputs from ChatGPT can vary even when the same prompt is used [9] [13]. Moreover, ChatGPT 3.5 has been shown to have poor response consistency when compared to ChatGPT 4 [4]. Some amount of randomness and chaos is inevitable in the AI generative algorithms in large language models. However, such variations in the ChatGPT output can generate confusion in interpreting the findings and lead to inconclusive understanding. The present study aims to examine the consistency and repeatability of gender bias in ChatGPT prompts if and when it occurs. Methodology To investigate the gender bias in ChatGPT, 11 stereotypically male-dominated and 11 stereotypically female-dominated professions based on the published reports [2] [11] were selected. Consistency metrics reveal the stability of the model’s behaviour under repeated testing. The consistency of ChatGPT responses was assessed by measuring responses across multiple iterations of the same prompt. For each profession, ChatGPT 3.5 was instructed to describe the character and the personality traits. For example, the prompt “I am writing a story and the protagonist is a nurse. Describe the character and personality traits” was the input. A total of 22 prompts were presented each day. To evaluate the presence of bias with certainty and to ensure that the generated responses are not a random single phenomenon that could have occurred on a particular day for any number of reasons, the 22 ChatGPT prompts were presented continuously for 10 days. The order of the prompt queries was randomised to prevent standardised responses. The task was to evaluate if the stereotype related to the profession was held by the ChatGPT 3.5. If the ChatGPT held a stereotype (i.e., the protagonist with the male or female-dominated profession was addressed by he/him or she/her, respectively), then the response was assigned a rating of 1. If the stereotype was not held or if the protagonist was addressed by "they/them,” then the response was assigned a rating of 0. A repeated measures ANOVA was administered to evaluate gender stereotypes in ChatGPT responses for female vs. male-dominated professions across 10 days. Python program was used to conduct the statistical analysis. The initial step involved converting the list values into arrays, a process achieved using the Numpy function np. Array. The code used two essential libraries, Numpy and Scipy. Numpy facilitated the efficient manipulation of arrays, while Scipy provided an assortment of statistical functions. Results Gender bias in ChatGPT 3.5 responses was examined for 11 stereotypically feminine and 11 stereotypically male-dominated professions over 10 days. Gender bias was assessed by determining if a stereotype commonly associated with female- or male-dominated jobs is supported. A rating of 1 or 0 was given when the stereotype for each gender was held or not, respectively. A stark difference in the gender stereotyping of female and male-dominated professions in the ChatGPT responses emerged across different days. Figure 1 shows the gender stereotype held by ChatGPT 3.5 in percentage for stereotypically female-dominated professions (red) and male-dominated professions (blue) for the same prompt repeated for 10 days for each profession. The figure provided below shows that the gender stereotype for all female-dominated professions was held repeatedly for all 10 days. On the other hand, the presence or absence of gender tereotypes for male-dominated jobs varied across 10 days. When the presence or absence of gender stereotypes in ChatGPT responses was averaged over 10 days for female and male-dominated jobs, the stereotype was held 100% for female jobs and 63% for male jobs (Figure 2), demonstrating a considerable gender bias for female jobs. Figure 1: Stereotype held by ChatGPT 3.5 in percentage for stereotypically female-dominated professions (red) and male-dominated professions (blue) when repeated for 10 days. Figure 2: Mean stereotype held by ChatGPT 3.5 in percentage for stereotypically female-dominated professions (red) and male-dominated professions (blue) for prompt repeated for 10 days.  The error bars represent standard deviation of the mean. A repeated measures ANOVA was administered to find if ChatGPT responses in female vs. male-dominated professions upheld the stereotype across 10 days. The statistical test showed that gender bias in ChatGPT responses significantly (F = 4.64; p <0.005), indicating that gender stereotyping of female and male-dominated professions differed dramatically across days. Figure 1 shows the variation (highest 81% to lowest 45%) in the percentage of stereotypes held for male jobs across 10 days. Post-hoc tests following Bonferroni corrections further showed how stereotypes in ChatGPT responses differed across days. For some days, like days 2, 4, or 8 (Figure 1), gender bias in ChatGPT responses for male-dominated jobs was as gender biassed as those for female-dominated jobs (p > 0.005), while on other days (days 3, 7, or 10), the responses were significantly less gender-biassed than female jobs (p < 0.005). Figure 3 below shows stereotypes held in percentage by ChatGPT for individual professions across 10 days. Figure 4 shows the distributions of pronouns (he, she, or they) assigned for different professions across 10 days. Figure 3: Stereotype held by ChatGPT 3.5 in percentage for individual stereotypically female-dominated (red) and male-dominated professions (blue). Figure 4: Percentage distribution of gender pronouns - He (blue), She (red) and They (grey) assigned by ChatGPT 3.5 across 11 stereotypically male-dominated professions As seen in Figure 3, all 11 stereotypically female-dominated professions were consistently assigned to females, and the pronoun she/her was used. On the other hand, of the 11 typically male-dominated professions, only two professions—cab driver and construction worker—were consistently considered as professions for males (Figure 3) and were assigned masculine pronouns “he/him “(Figure 4) by ChatGPT for all 10 days, while financial analyst and sales manager were considered more gender-neutral jobs and mostly assigned the pronoun “they.” Notice in Figure 3 that for stereotypically male-dominated jobs, gender bias was highest for professions that require more manual labour skills and are often referred to as “blue-collared jobs like a construction worker, cab driver, or electrician, and bias reduced and reversed as the job shifted to professions that need advanced education like CEO and civil engineer. Discussion The study explored the presence and repeatability of occupational-related gender bias in ChatGPT 3.5-generated responses. The present study showed that even though ChatGPT responses have an undeniable gender bias for stereotypically female-dominated jobs, the gender bias for male-dominated jobs varied when repeated across 10 days. A trend of strong maintenance of gender bias in female jobs but a variable, sometimes reversible gender bias for male jobs has been reported by Spillner (2024). This may reflect the current societal trend where it is easier and more acceptable for the female population to make their way into male-dominated fields than for males to seek stereotypically female jobs. For example, it is more acceptable for females to become firefighters and CEOs than for males to become elementary teachers, caregivers, or librarians. The current findings emphasise how the stereotypes and gender bias upheld by society are further perpetuated by the ChatGPT. Moreover, the shifting of the gender bias from male to female in the stereotypically male jobs was seen more for the professions that need advanced education, like CEO and civil engineer, than professions that require more manual labour skills, like a construction worker, cab driver, or electrician. Similar findings were reported by Spillner (2024). The study showed that the male gender bias remained for stereotypically “blue-collared” male jobs, while the bias reversed and female characters were assigned to the “white-collared” jobs. The study’s author attributes the bias reversal to a possible effect of correction and sometimes overcorrection of gender bias in language models triggered by awareness and human feedback. It was of interest to see if ChatGPT gender bias is maintained or changes when repeated over time for female or male-dominated jobs. The same prompt for each profession was repeated in new sessions for 10 days to strengthen the accuracy of the response and account for any randomness that would influence a single data point. It was interesting to see that gender bias for female jobs selected in this study was 100% repeatable. However, gender bias for male jobs varied across 10 days. Some days the gender bias in the ChatGPT responses between male and female jobs was comparable, and some days there was significantly reduced bias for male jobs compared to female jobs. This finding brings attention to the variability in ChatGPT responses and the need to exercise caution when interpreting the findings based on a single ChatGPT response. Conclusion Generative AI like ChatGPT is a powerful tool that has a lot of potential to enhance all walks of our lives. Moreover, the influence of such generative AI tools is only going to increase exponentially in the future. Therefore, it is important to understand the role of ChatGPT in perpetuating gender bias in our society. In our present study, the consistency of the gender bias in ChatGPT outputs, if present, was explored by studying multiple iterations of the same prompt over a period of time. Our study concludes that outputs of ChatGPT behave differently for stereotypically male-dominated jobs than female-dominated jobs. Our findings consistently show that there is an undeniable bias for female jobs, while bias for male jobs varies on different days. The study throws light on the importance of using multiple responses rather than a single data point while interpreting results from large language models like ChatGPT. Further research is needed to understand the repeatability and variability in AI tools like ChatGPT and extend these findings in interpreting and correcting for the gender bias in these tools. References Babaei, Golnoosh, David Banks, Costanza Bosone, Paolo Giudici, and Yunhong Shan. 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Author: Rachana R What is epigenetics? Epigenetics is the study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.The term “epigenetics” came into general use in the early 1940s, when British embryologist Conard Waddington used it to describe the interactions between genes and gene products, which direct development and give rise to an organism’s phenotype. "Epi-"means ‘on or above’ in Greek,and "epigenetic" describes factors beyond the genetic code. Epigenetic changes are modifications to DNA that regulate whether genes are turned on or off.Epigenetic change can have more damaging effects that can result in diseases like cancer. At least three systems including DNA methylation, histone modification and non-coding RNA associated gene silencing are currently considered to initiate and sustain epigenetic change.New and ongoing research is continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases. What is epigenome? Epigenome is all the genes plus everything that regulates the usage of those genes. An epigenome changes over time. It’s both advantageous and disadvantageous. It’s advantageous that things like nutritious food, exercise and manageable stress can result in epigenetic changes that can promote health. But other factors like processed foods, smoking and lots of stress can cause epigenetic changes that can harm health. The History of Epigenetic Research During the 1990s there became a renewed interest in genetic assimilation. This led to elucidation of the molecular basis of Conrad Waddington’s observations in which environmental stress caused genetic assimilation of certain phenotypic characteristics in Drosophila fruit flies. Since then, research efforts have been focused on unraveling the epigenetic mechanisms related to these types of changes. Currently, DNA methylation is one of the most broadly studied and well-characterized epigenetic modifications dating back to studies done by Griffith and Mahler in 1969 which suggested that DNA methylation may be important in long term memory function. Types of epigenetic modifications The principal type of epigenetic modification that is understood is methylation.Methylation can be transient and can change rapidly during the life span of a cell or organism.The specific location of a given chemical modification is also very important.Other largely permanent chemical modifications also play a role; these include histone acetylation,ubiquitination and phosphorylation. Epigenetic inheritance It is evident that at least some epigenetic modifications are heritable, passed from parents to their offspring in a phenomenon that is generally referred to as epigenetic inheritance or passed down through multiple generations via transgenerational epigenetic inheritance. The mechanism by which epigenetic information is inherited is unclear; however, it is known that this information, because it is not captured in the DNA sequence, is not passed on by the same mechanism as that used for typical genetic information. What are the diseases linked to epigenetics? Aging Diseases associated with aging. Disorders affecting the neurological system(including syndromes which affect intellectual ability) Cancer Asthma Autoimmune diseases Impact of epigenetics on biomedicine From years of research, researchers have recognized that the epigenome influences a wide range of biomedical conditions. This new perception has opened the door to a deeper understanding of normal and abnormal biological processes and has offered the possibility of novel interventions that might prevent certain diseases. Researchers have understood that epigenetic mechanisms play a key role in defining the “potentiality” of stem cells. As those mechanisms become clearer, it may become possible to intervene and effectively alter the developmental state and even the tissue type of given cells. Compared to other areas of study, epigenetics is still fairly new. And there’s a lot yet to be discovered.Scientists continue to explore the relationship between the genome and the chemical compounds that modify it. In particular, they are studying the effects that epigenetic modifications and errors have on gene function, protein production, and human health. References : 1.What is epigenetics. 2017. “Epigenetics: Fundamentals, History, and Examples | What Is Epigenetics?” What Is Epigenetics? 2017. https://www.whatisepigenetics.com/fundamentals/. 2.MedlinePlus. 2021. “What Is Epigenetics?” Medlineplus.gov. June 11, 2021. https://medlineplus.gov/genetics/understanding/howgeneswork/epigenome/. 3.Rogers, Kara, and Judith L Fridovich-Keil. 2018. “Epigenetics | Definition, Inheritance, & Disease.” In Encyclopædia Britannica. https://www.britannica.com/science/epigenetics. 4.“What Is Epigenetics?” n.d. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/epigenetics.

Author: Asal Hajimohammadi Rayeni

Co-authors: Huaxuan Chen, Adithya Chakravarthy, Rachel Woo First published: June 2020 Abstract The Zika virus is a mosquito-borne virus that has affected 65 countries since 2015. There are currently no cures for the virus, so at-risk populations rely solely on preventative methods such as nets and insecticide sprays, with limited effectiveness. COBWEB, a computer simulation software, was used to determine the effectiveness of an introduction of the insecticide “permethrin” in the Brazilian city of Olaria, where the Zika virus is particularly virulent. Due to its flexibility and wide array of parameters, COBWEB was also able to model the effects of permethrin resistance on Zika transmission. The result was that permethrin significantly reduced fatality rates from the Zika virus and permethrin with resistance was still comparatively better than the control. This information is helpful, as it can be applied to other areas where the Zika virus is especially virulent, and serve as a potential solution to this emerging disease. Introduction Vector-borne infectious diseases are human illnesses caused by vectors, which are carriers of diseases or medicine. Vectors do not cause disease, but they spread infection when they’re passed from one organism to another. These vector-borne diseases are typically transmitted by animal hosts, and they make up a significant portion of the world’s disease burden. Indeed, nearly half of the global population is infected with at least one type of vector-borne disease pathogen.[1] Mosquitoes are the most common disease vector, and they spread pathogens by ingesting them from an infected host during a blood meal and then injecting them into a new host.[2] The Zika virus has spread rapidly across Eastern Brazil and Mexico by mosquitoes since its first identification in Africa in 1947. As of 22 June 2016, 61 countries and territories have reported continuing Zika transmission.[2] In Brazil alone, there have been an estimated 440 000 – 1 300 000 cases of Zika[3]. Propagated by the vector Aedes aegypti, or the yellow fever mosquito, the Zika virus can result in a number of symptoms, ranging from rashes and joint pain to total body paralysis.[4] When pregnant women are infected with Zika, their fetuses often display birth defects such as microcephaly, a rare neurological condition resulting in abnormal head sizes; in Paraiba, a province in Northeastern Brazil, the health ministry released statistics revealing that 114 babies per every 10,000 live births were born with suspected microcephaly – more than 1% of all newborns.[5] Since there are no solutions to the Zika virus as of now, preventative measures such as nets are used to prevent undue exposure to the disease vector. Permethrin is a synthetic form of the naturally occurring insecticide, pyrethrum, which comes from Chrysanthemums. It is an insecticide to mosquitoes, ticks and other insects.[6] Its usage is highly effective, and it was shown through a study by the Institute of Medicine Forum on Microbial Threats that when lightweight uniforms from the military are treated until moist (approximately 4.5 oz) of permethrin (concentration 0.5%), it gives them 97.7% protection from mosquito bites.[1] Using the large-scale biological simulation software “COBWEB”, the effectiveness of the insecticide “permethrin” in reducing the spread of Zika was modelled. This simulation focuses on the city of Olaria, Brazil, where the Zika virus is especially virulent. Furthermore, the study examines the growing trend of permethrin resistance in the Aedes aegypti vector, which affects the efficacy of insecticides in preventing further spread of Zika. Three different simulations were created for comparison purposes; one was the control, one had the application of permethrin, and one had permethrin with the added factor of insecticide resistance. In comparing the three simulations, the research team was able to determine the best way of dealing with the emerging disease. Methods and Materials COBWEB, which stands for Complexity and Organized Behaviour Within Environmental Bounds, is an agent-based, Java coded software, used to study interconnected and interdependent components of complex systems in numerous fields of study. COBWEB explores how components, such as mosquito and human populations, change and adapt as different variables are manipulated. It is used to create virtual laboratories and facilitate the study of how different populations of agents are influenced by various environmental changes. This permits the assessment of growth, decline, or sustainability of the populations within their environment over time. Additionally, abiotic factors such as permethrin can be included to study the effects of its introduction in the virtual laboratory. The effect of human migration on Zika transmission rate can be simulated using COBWEB by translating population and treatment circumstances into agents and environmental factors. Based on data by the World Health Organization, the Zika virus has been prevalent in Brazil. However, not all areas of Brazil have reported evidence of the Zika virus. The city of Olaria was selected as the environment because it has the highest concentration of the virus; in the 0.79 area covering the average flight range of Aedes mosquitoes, it was found that there were 3,505 and 4,828 female mosquitoes in the MosquiTrap and aspirator, respectively, totalling 8,333.[7] By applying Olaria’s population to transmission rates, the population variance upon addition of the pesticide was observed. A. Setting up COBWEB: Assumptions and/or arbitrary figures Some arbitrary numbers and assumptions were made for a few parameters in COBWEB. In the environment tab in COBWEB, three Agent types were chosen (Figure 1). Agent 1 was assigned to represent the human population of Olaria, while Agent 2 was set to represent mosquitos; Agent 3 represents the permethrin, which is a control factor in the experiment. Additionally, it was decided that the environment would be 180 x 180 in dimensions. By increasing the environment and space for the various components to interact, more reliable data is produced. All other parameters were kept in their default state. Figure 1: This is where the desired simulation is configured. This can exemplify a number of systems such as a section of a forest, ocean, city or body part that the user wants to study. The environment is represented on a 2D grid. This represents the city of Olaria. This experiment had three simulations. The first (the control) was a simulation featuring just humans and the vector. The second (Simulation 2) featured humans, the vector, and the insecticide permethrin. The last (Simulation 3) featured humans, the insecticide-resistant vector, and permethrin. For ease of explanation, this paper will first explain the Control, Simulation 2, followed by Simulation 3 (Figures 2 – 7). Several tabs on the COBWEB software were used. The “resources”, “agents”, “food web”, and “diseases” tabs were the main factors that were manipulated for the purposes of this study. The “resources” tab was used to sustain the various populations (in this case, mosquitos, humans, and permethrin) and ensure that they had the ‘resources’ to function in the experiment. The “agents” tab was used to model the various populations and their respective roles within the environment. In order to ensure accuracy, the population of Olaria and the mosquito count were determined and inputted as the agent counts. The “food web” function was used to control the interactions and interrelationships between the agents. Finally, the “disease” function was used to study the effects of Zika on the fatality rates in Olaria and the transmission of microcephaly. The contact transmission rate, child transmission rate, and use of permethrin as a “vaccine” with a specific effectiveness were used to study the effects that permethrin has on the simulation and the effects that Zika has on future populations. The tick number at the top of the screen represents the time period in which a simulation runs. This number, which was kept constant in all three models, is relative and is representative of a sample time period. The numerical time is not the most important, as the trend over a constant period of time provides the most conclusive and useful results. However, for the purposes of this simulation, the tick number was chosen to represent days, so each tick represented one day of the year. CONTROL: Vector and Humans, with no Permethrin Figure 2A: In the “Resources” tab of COBWEB, certain resource amounts were allotted to the different agents to ensure they have enough ‘food’ to function and progress through the experiment. “Agent 1” corresponds to the human population and “Agent 2” corresponds to the mosquito population. Figure 2B: In the “Agents” tab of COBWEB, the counts of the different agents, which were determined from research, were inputted to ensure reliability of the results. The other factors were determined upon experimentation and done in ratios to depict the patterns of the agents. Figure 2C: In the “Food Web” tab of COBWEB, the interconnectedness between the two agents was depicted. For instance, “Agent 2” has a checkmark for “Agent 1” because the mosquito population affects the human population. Figure 2D: In the “Disease” tab of COBWEB, the infected fraction and the child transmission rate (as of 2015) were inputted. Since the Zika virus leads to microcephaly, a birth defect, the percentage of children who have parents infected with the virus and that acquire the condition was inputted. SIMULATION 2: Vector with Permethrin Figure 3: To reiterate, the food web function was employed to depict the interactions between the agents and the three varieties of food. Agent 3 (permethrin) “consumes” mosquitoes to signify that it kills them. Food 1 represents food both mosquitoes and humans need to survive; this mostly signifies water since it is the resource that both agents need to the greatest extent to survive. Food 2 represents food just meant for mosquitoes. “Food 3” is there to simply keep permethrin levels relatively consistent throughout the simulation’s progress; it can be seen as a source of permethrin. Figure 4: The next step was setting the agent parameters. Agent 1 represents the human population of 1893 in Olaria, Brazil[8], Agent 2 is the mosquito population of 2500, or the average of the female population size[9], and Agent 3 is the control group, or in this case the insecticide. The breed energy is higher for Agent 1 to signify that ‘more energy’ is required to reproduce, concluding that birth rates of humans are lower than that of mosquitos. Figure 5 : The initially infected fraction was approximately 7%[9], the contact transmission rate was set as the default, and the child transmission rate was 15%, as not all babies exposed to the Zika virus would be infected; the average was taken of the predicted 10-20% chance of infection.[5] For agent 2, the factors were all kept constant. This was also seen for agent 3 but with exception to the effectiveness rate of 97.7%, as the pesticide gives 97.7% protection from mosquito bites. As seen in Figure 3, agent 3 ‘eats’ agent 2, so the contact transmission rate is translated in that respect. SIMULATION 3: Insecticide-Resistant Vector with Permethrin Figure 6: All the factors are identical to that of the second simulation, except in the third where the vector’s resistance to permethrin is modelled in under the “vaccine effectiveness” tab. According to various experiments that have studied insecticide resistance of Aedes aegypti vector, the vector can show resistance ranging from 90% to 95% of its interactions with permethrin.[10] The vaccine effectiveness was averaged as 93% to represent the mean and most common resistance statistic. Results To effectively compare the three simulations, the tick count (i.e. the time step in the model) was consistently kept at 800. Since this number is quite large, it ensures an observable trend; there could be significant changes in an ecosystem over short periods of time which may skew the findings and thus, the results. CONTROL: In the control simulation, it was seen that there was a rapid growth in the mosquito population and a rapid decrease in the human population. This can be attributed to the fact that without interference, there is exponential growth in the number of mosquitos, and thus an exponential growth in the interactions between mosquitoes and humans. Figure 7A : The control simulation examined the effects of the Zika virus in Olaria without permethrin. In this simulation, the tick count number was 800, which was representative of 800 days. The graph above depicts the population of humans over time, which is steadily decreasing. Figure 7B: The graph above depicts the population of mosquitoes over time, which increases and then decreases after the population reaches 7000. SIMULATION 2: The second simulation also had a tick count of 800 for consistency. In this simulation, the human population experienced an initial decrease in population, followed by a steady increase by about 4 times the initial population (Figure 5). The mosquito population rapidly declined and then levelled out at zero after around 411 days (Figure 6). Once the mosquito population hit zero, there was an observable spike in the human population, as expected. The supply of permethrin was made to be steady and constant over time to maximize its influence on the population. Figure 8 : This graph shows the increase in human population over a time span of 800 days. Figure 9. This graph shows the decrease in the Aedes aegypti population over a span of 800 days. SIMULATION 3: The third simulation, which also had a tick count of 800 days, displayed the resistance development of the Aedes species mosquito with insecticide. Because mosquitos “learn” and eventually develop resistance to certain treatments, it is important to study their effects over time and to what degree the resistance impinges on the effectiveness of permethrin. Figure 10 : The population of Aedes aegypti vector spikes before declining to zero unlike the second simulation (Figure 5), where the mosquito population declines without spiking; this is attributable to the implementation of insecticide resistance. Figure 11: The graph above depicts the trend of the human population in Olaria when the city is under the subjection of permethrin-resistant mosquitoes. The human population rises steadily, but at a slower rate than the second simulation (Figure 5). Discussion From the study, it is evidenced that Zika is best controlled with permethrin. Although the consideration and inclusion of permethrin resistance created a deviance from the results with sole permethrin application, the results were still comparatively better than the control; the human population increased and the mosquito population decreased to a greater extent when permethrin was applied. Additionally, in comparing the graphs depicting simulation 3 and the control, it can be seen that simulation 3 yields a smaller fatality rate for humans and a greater fatality rate for mosquitos. However, in consideration of insecticide resistance, the results and trends were not as significant as those without. For instance, the population of the Aedes aegypti spiked before declining to zero. This was likely due to insecticide resistance, which allowed the initial population of mosquitoes to further propagate before declining, as expected. Also, the human population in the third simulation rose steadily but at a slower rate than in the simulation without insecticide resistance. This was likely due to insecticide resistance, which could’ve made it easier for mosquitoes to infect humans and thus, slowed population growth. Although care was taken to ensure error was minimized, there are a few inevitable errors that could have affected the data from this study. Firstly, the model does not account for certain environmental factors such as differences in temperature, humidity, and elevation, all of which could influence the reproductive and survival rates of the Aedes aegypti vector. More specifically, the rise of global temperatures as a result of climate change would undoubtedly significantly affect the vector populations. As the crisis is affecting the viability of populations, it can affect the results of the survivability and reproduction of mosquitoes. Extreme weather can also drastically influence the populations of humans and mosquitoes, making the data less reliable. These factors could be included in the next iteration of this work. Besides environmental factors being neglected from the study, numerous socio-economic factors were not factored into the study. The methods assumed that women and men were equally susceptible to Zika, because biologically speaking, their chances of contracting the virus were equal. However, in many rural areas such as Olaria, the city in question, a significant number of women work in the fields and in adverse conditions, thereby increasing their chances of exposure to the vector; about 70% of rural people in Brazil engage in agricultural employment, and female-headed households, which are becoming increasingly common, make up 27% of the poor rural population. Thus, had these environmental and socio-economic elements been factored into the simulation, the simulation results could have been different. Another potential source of error was with the averaging of the effectiveness of permethrin, which created a sample rate as opposed to a range. However, the average was the most prevalent among the tests, so it was used to find the main and most prevalent occurrence in the range of possibilities. Furthermore, in the real world, a small population of mosquitoes may survive because of insecticide resistance, and pass on the disease; in this way, the number of mosquitoes who can transmit the Zika virus could grow exponentially. However, the COBWEB software isn’t able to factor that circumstance into the simulation, so the model features all mosquitoes dying out. This additional factor would have affected the mosquito populations over time, but the model does give a guideline and approximate trend for the reduction of mosquitoes. Although there may have been discrepancies with the data, COBWEB still had the ability to produce results similar to the data provided by the WHO. In the future, factors such as the impact of climate change and the migration of people who have the disease could be studied, and comparisons can be made between Permethrin and other solutions for mitigating the spread of the Zika virus. Conclusion There is potential for more studies to be performed using the current Zika models in COBWEB. The insecticide permethrin has shown promising ability to decrease the population affected by Zika in Olaria. This can be applied to all of Brazil, and extend to other countries where Zika is virulent. This research explicates permethrin as an effective barrier to the initial interaction of humans and mosquitoes. This study suggests an alternative solution to the existing options of nets and human reproduction practices. The next step is to explore how climate change can affect these agents, and how encouraging governments to mitigate the effects of the changing climate can impact the population\’s health and well-being. Another area of future study deals with the effectiveness of a Zika vaccine, as a study has shown 17 out of 18 tests on monkeys to be effective. Overall, permethrin was shown to be effective in reducing the interactions between humans and mosquitoes, and concurrently reducing the cases of Zika. This research can be applied to other countries, such as Ecuador, where the Zika virus is also very virulent. Acknowledgements : A great thank you to Dr. Brad Bass, a status professor at the University of Toronto and Nobel Peace Prize Co-recipient, for developing the COBWEB software and for mentoring the team along the way. References : Threats, Institute. 2008. \”Summary And Assessment\”. Ncbi.Nlm.Nih.Gov . https://www.ncbi.nlm.nih.gov/books/NBK52939/ . \”Zika Situation Report\”. 2016. World Health Organization. http://www.who.int/emergencies/zika-virus/situation-report/23-june-2016/en/ . Bogoch, Isaac, Oliver Brady, Moritz Kraemer, Matthew German, Marisa Creatore, and Manisha Kulkarni. 2016. \”Anticipating The International Spread Of Zika Virus From Brazil\”. Europe PMC. http://europepmc.org/articles/pmc4873159 . \”What We Know About Zika\”. 2018. CDC. https://www.cdc.gov/zika/about/ . \”More Brazilian Babies Born With Defects\”. 2018. BBC News. http://www.bbc.co.uk/news/world-latin-america-35368401 . Bloomington, Indiana, Indiana Bloomington, IU Bloomington, and Indiana University. 2018. \”Insect Precautions – Permethrin, Deet, And Picaridin: IU Health Center\”. Healthcenter.Indiana.Edu . http://healthcenter.indiana.edu/answers/insect-precautions.shtml . Massad, Eduardo, Marcos Amaku, Francisco Countinho, Claudio Struchiner, Luis Lopez, Annelies Wilder-Smith, and Marcelo Burattini. 2018. Estimating The Size Of Aedes Aegypti Populations From Dengue Incidence Data: Implications For The Risk Of Yellow Fever Outbreaks. Ebook. Accessed November 18. https://arxiv.org/pdf/1709.01852.pdf . \”Olaria (Municipality, Brazil) – Population Statistics, Charts, Map And Location\”. 2018. Citypopulation.De . https://www.citypopulation.de/php/brazil-regiaosudeste-admin.php?adm2id=3145406 . Maciel-de-Freitas, Rafael, Alvaro Eiras, and Ricardo Lourenco-de-Oliveira. 2008. \”Calculating The Survival Rate And Estimated Population Density Of Gravid Aedes Aegypti (Diptera, Culicidae) In Rio De Janeiro, Brazil\”. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-311X2008001200003 . Rodriguez, Maria, Juan Bisset, and Ditter Fernandez. 2007. \”Home\”. Bioone.Org . http://www.bioone.org/doi/abs/10.2987/5588.1 . About the Authors Huaxuan Chen is a student who is extremely passionate about global health, law, chemistry, and development. She is also an SDGs advocate who was a Canadian Youth Representative at the Commission on the Status of Women Youth Forum and PGA High Level Event on Education; she focuses mainly on climate action, gender equality, and education. She enjoys using her knowledge and skills to help others. She is now studying statistics at Duke University. Adithya Chakravarthy is currently a third-year student at the University of Toronto in the Engineering Science Program. He is very passionate about computer modeling of complex systems. Apart from science, he is also deeply involved in debating, representing Canada on the Canadian National Debate Team at the 2018 World Schools Debating Championships in Zagreb, Croatia. He is also a vocalist in the Indian Classical music tradition, having performed in many concerts across North America and India. Rachel Woo is starting her Masters in Public Health at Waterloo in Fall 2020. Her research interests include data visualization, and games for health.

Author: Kai Sun Yiu Abstract The summer of 1996 sparked the beginnings of limitless, scientific potential. Dolly the sheep was born from her surrogate mother, after being cloned by Sir Ian Wilmut and his team from a six-year-old Finn Dorset sheep [1]. Dolly was formed through genetic material, extracted from a Finn Dorset Sheep, being placed into an enucleated egg cell [2]. An embryo was formed following a series of meiotic divisions, and 148 days (about 5 months) after being implanted into the surrogate mother’s uterus, Dolly was born [3]. However, Dolly wasn’t the first mammal to be cloned, with that title being held by two other sheep, Megan and Morag, who had been cloned a year earlier from embryonic and fetal cells [2]. However, this didn’t undermine her significance, through being the first mammal cloned from an adult cell, rather than an embryonic cell. Dolly’s existence disproved past assumptions that specialized cells could only do a certain job, with Dolly being born from a specialized mammary cell which somehow held the genetic information to create an entirely new sheep [4]. This sparked new potential for medicine and biology through the development and research of personalized stem cells, which will be explored within this article through the differences between embryonic stem cells and adult stem cells.  Introduction Human cloning can be defined as the creation of a ‘genetically identical copy of a previously existing human,’ or the reproduction of cloned cells / tissue from that individual [5]. Through human cloning, we can gain stem cells from the cloned blastocyst and treat these cells to differentiate into any cells we need for medical purposes. However, this understandably has ethical complications which have made it difficult for scientists to carry out lots of stem cell research.  This article focuses on the more complex ethical standpoints around stem cell research through some forms of therapeutic cloning, using SCNT (Somatic cell nuclear transfer) and iPSCs (Induced pluripotent stem cells). While SCNT uses embryonic stem cells, iPSCs utilizes the adult stem cells we possess in our bodies to repair damaged cells and tissues. However, both types of cells contain major ethical complications through their uses, allowing this article to tackle the conflict between stem cells' infinite possibilities against their downsides and ethical considerations.  An insight into modern stem cell research - SCNT and iPSCs Somatic cell nuclear transfer (SCNT) refers to the process used by both reproductive and therapeutic cloning to produce a cloned embryo. SCNT was first used by Sir Ian Wilmut and his team when cloning Dolly, the sheep: The nucleus which contains the organism’s genetic material (DNA) of a somatic cell is removed The nucleus from the somatic cell is then inserted into the cytoplasm of an enucleated egg cell The egg which contains the nucleus stimulated with electric shocks to encourage mitotic division After many mitotic divisions, the cell forms a blastocyst, which divides further until it eventually forms an embryo [6] SCNT is utilized by scientists and researchers worldwide in an attempt to obtain stem cells from the cloned embryo, and use it through regenerative medical practices [6]. A common use of stem cells in regenerative medicine would include the treatment of Parkinson’s disease, where stem cells can restore the production of dopamine in the brain. The in-depth process includes gaining undifferentiated stem cells from the embryo and treating them to differentiate intro dopamine producing nerve cells to treat Parkinsons [7].  With the use of SCNT, autologous cells can be formed. Autologous cells are formed from the stem cells of the same individual, meaning the therapeutic material is cloned from the patient, allowing there to be no need for immunosuppressive treatments when differentiated cells are injected into the body [7]. This is due to the autologous cells not being foreign cells, therefore resulting in no probability of the immune system rejecting and damaging the newly introduced stem cells into their body. With stem cell’s ability to ‘treat many human afflictions, including ageing, cancer, diabetes, blindness and neurodegeneration,’ why is there such a lack of breakthrough research on stem cell therapy [8]? Induced pluripotent stem cells (iPSCs) refer to cells that have been derived and reprogrammed from adult somatic cells (normally taken from a patient bone marrow) [9]. These cells have been altered through the introduction of genes and other factors into the cells to make them pluripotent; this arguably makes them like embryonic stem cells, so they similarly carry the same ethical problems [9].  iPSCs are not only seen as unethical, but also take 3-4 weeks of careful lab work to form [10]. The process is extremely slow and inefficient and has a success rate lower than 0.1% [10]. Nonetheless, there are limitless applications for iPSCs such as regenerative medicine, disease modeling and gene therapy.  Similarly to SCNT, the main advantage of iPSCs is the ability to eliminate any possibility of immune system rejection. The iPS cells are directly generated from the somatic cell of the person’s own body, so there can’t be an immune response to them, as the cells are genetically tailored precisely for the patient they are taken from [12]. The main problem of iPSC is the risk of mutation during the reprogramming of the somatic cells, which can lead to the formation of a cancerous tumor [11]. However, we still need to explore the ethical standpoints in the formation of pluripotent stem cells for research and regenerative science.  The ethics - SCNT Through the process of SCNT, we can gain embryonic stem cells from a three-day old embryo. The extraction of the stem cells destroys the blastocyst, a 3-5 day old embryo which can be observed as a cluster of around 180 cells growing within a petri dish, before it fully forms into a fetus [13]. The blastocyst is used as it is at such an early stage of the formation of the fetus, so the cells have not yet differentiated so is arguably ‘not alive’ [13].  The ethical argument against the extraction of stem cells is the fact that the destruction of an embryo is arguably killing a fully developed human being. We can look at the position of Senator Sam Brownback, who saw ‘a human embryo...as a human being just like you and me. [13]’ The ethical standpoint around the destruction of embryos is so varied, with George Bush using his veto when US Congress passed a controversial bill, which permitted more funding towards research that used embryonic stem cells [14]. All these ethical considerations surrounding the formation of stem cells are difficult to forget, yet we still need to remember the immense medical and research potential they carry.  Embryonic Stem Cell Research around the Globe - SCNT  Map Explanation [15] Dark Brown = ‘permissive’ - Allows various embryonic stem cell research techniques such as SNCT. Light Brown = ‘flexible’ - Lots of restrictions, with embryos only being used under extreme conditions. SCNT is completely banned with human reproductive cloning not allowed.  Yellow = no policy or restricted policy - Outright prohibition of embryonic stem cell research Black Dots - Leading genome sequencing research centers in the world  The map above illustrates the flexibility around the globe when it comes to the use of embryos during stem cell research. Even in the very few countries which have leading facilities and institutions, there are massive restrictions on the usage of embryos. Even looking at Britain, who managed to vote on the easing of restrictions on the use of embryonic stem cells in 2001, we still have only 7 laboratories across the country [16], [17].  The various ethical considerations around the destruction of an embryo makes stem cell research difficult to legalize and even fund. However, the use of stem cells can be arguably seen as the most promising research done for regenerative medicine in the last century. Imagine the ability to cure diseases through replacing cells damaged by infection or being able to grow organs from stem cells to transplant into the thousands of patients waiting for an organ donor.  What if there was a way to form somatic stem cells without the destruction of an embryo? The ethics - iPSCs  Pluripotent stem cells have the ability to form all three of the basic layers in our body (ectoderm/endoderm/mesoderm), which allows them to potentially produce any cell or tissue needed [18]. There are four types of pluripotent human stem cells [19]: Embryonic stem cells Nuclear Transplant stem cells Parthenote stem cells Induced stem cells All pluripotent human stem cells, apart from Induced stem cells, require human eggs to create. This means that the use of pluripotent human stem cells is limited by ethical considerations; however, induced pluripotent stem cells are different in the way they don’t require the destruction and harm of an embryo.  These iPSC were discovered over ten years ago by Shinya Yamanaka. The Nobel Prize winner managed to revolutionize biological research by developing a technique to convert adult mature cells into stem cells using the four key genes OCT3/4, SOX2, KLF4, MYC, which are now known as the ‘Yamanaka factors [20].’ iPSCs as a research area has been greatly explored by thousands of researchers around the world, due to the production of the cells being non-controversial in their ability to be derived straight from adult cells rather than embryonic cells. There have been numerous applications of iPSCs in therapeutic medicine. In 2014, RIKEN (The largest scientific research institution in Japan), treated the first patient with iPSC derived retinal sheets, which were able to help with visual function [21]. 2 years later, Cynata Therapeutics (A biotech company), produced iPSC derived product for the treatment of GvHD (Graft versus host disease) [21]. GvHD is a life-threatening disease which can occur when there are complications during stem cell and bone marrow transplants [21]. When the grafted cells are transplanted into the patient, they begin to produce antibodies which interact with the host antigens. This triggers an immune response which may result in an inflammatory cascade, which can cause irreversible organ dysfunction and even death [22].  The unlimited medical possibilities iPSCs unlock, paired with the lack of ethical problems they face, makes IPSCs the perfect way to bring stem cell therapy to the masses.  However, it is not so simple, with the main issue of iPSCs is the need for retrovirus to form these stem cells [23]. The retroviruses used in forming the iPSCs can insert their DNA anywhere in the human genome and trigger cancerous gene expression when transplanted into the patient [23]. Furthermore, the success rate of reprogramming somatic cells into iPSCs is around 0.1%. Not only this, but iPSCs have a strange tendency to not always differentiate, making them much less reliable and successful than embryonic stem cells [23].  Nonetheless, research into iPSCs has developed rapidly over the past few years, with scientists and researchers slowly making stem cell therapy using iPSCs available to the public.  The Pros and Cons of Embryonic Stem Cells and Induced Pluripotent Stem Cells  Embryonic Stem Cells Induced Pluripotent Stem Cells   Pros Can maintain and grow for 1 year or more in culture Established protocols for maintenance in culture ESCs are pluripotent cells that can generate most cell types By studying ESCs, more can be learned about the process of development Abundant somatic cells of donor can be used Issues of histocompatibility with donor/recipient transplants can be avoided Very useful for drug development and developmental studies Information learned from the “reprogramming” process may be transferable for in vivo therapies to reprogram damaged or diseased cells/tissues  Cons Process to generate ESC lines is inefficient Unsure whether they would be rejected if used in transplants. Therapies using ESC avenues are largely new and much more research and testing is needed If used directly from the ESC undifferentiated culture prep for tissue transplants, they can cause tumors (teratomas) or cancer development  Methods for ensuring reproducibility and maintenance, as differentiated tissues are not certain. Viruses are currently used to introduce embryonic genes and has been shown to cause cancers in mouse studies  Ethical Concerns To acquire the inner cell, mass the embryo is destroyed Risk to female donors being consented iPS cells have the potential to become embryos if exposed to the right conditions A comparative table between Embryonic Stem cells and Induced Pluripotent Stem Cells [26] Stem Cell Therapy Today  Although no one has been cured of Parkinson's disease (PD) yet, the research from institutions around the world have shown significant development in recent years with ‘experimental treatment.’ On the 13th of February 2023, embryonic stem cells (most likely obtained through SCNT) derived healthy, dopamine producing nerve cells, which were transplanted into a patient with Parkinson’s at Skåne University Hospital, Sweden [24]. This marks an important milestone for all stem cell research, with the transplantation of the nerve cells being performed perfectly, shown by magnetic resonance imaging (MRI) [24].  The STEM - PD trial at Lund University (The first in-human trial to test the safety of stem cells for Parkinsons) is continuing to replace lost dopamine cells with healthy ones, manufactured from embryonic stem cells [24]. Parkinson's disease slowly affects the nervous system, due to the loss of nerve cells in the substantia nigra in the brain. Nerve cells are crucial for the production of dopamine, so the implantation of nerve cells helps regulate brain activity and function by secreting regular levels of dopamine. STEM - PD aims to move from their first human trial all the way to global treatment around the world [24]. This latest success in the use of embryonic stem cells further pushes researchers around the world, with stem cells soon to unlock cures for multiple diseases, in addition to aiding with the worldwide shortage of organs.  In Early 2023, researchers were able to differentiate neurons from induced pluripotent stem cells (iPSCs) [25]. The usage of iPSCs made it an arduous task, with the team needing to firstly differentiate the iPSCs into motor neurons, before placing them into coatings of synthetic nanofibers containing rapidly moving dancing molecules [25]. These mature neurons help aid the body’s nervous system, through sending rapid electrical signals around our body through tiny structures known as nerves. Within the near future, researchers believe that these mature neurons can be transplanted into those suffering with spinal cord injuries as well as neurodegenerative diseases (ALS, Parkinsons, Alzheimer's, Sclerosis) [25]. This new advancement in the usage of iPSCs allows scientists to research ethically sound ways of using stem cells for the treatment of all diseases. Conclusion Use of stem cells in repairing damaged cells/tissues, research into understanding diseases and testing for new drugs gives them incredible value in research and regenerative medicine. As the research for regenerative medicine improves, the success rate in the use of stem cells will gradually grow, which will hopefully loosen the tight legal grasp over the use of ESC (embryonic stem cells) and iPSCs due to their ethical problems (As seen in the table above), in either destroying and embryo or theoretically being from an embryo in iPSCs as they can be derived into an embryo.  Researcher and scientists should strive to refine existing stem cell formation techniques, and through the difficult legal ties, battle their way to the final aim of having stem cells with the ability to differentiate into any cell needed to cure any disease, form any organs to be used in transplants, and research into greater depth the difficulty in battling certain diseases.  References [1] Weintraub, Karen. “20 Years after Dolly the Sheep Led the Way-Where Is Cloning Now?” Scientific American, July 1, 2016.  https://www.scientificamerican.com/article/20-years-after-dolly-the-sheep-led-the-way-where-is-cloning-now/ [2] “The Life of Dolly.” Dolly the Sheep. Accessed November 26, 2023. https://www.ed.ac.uk/roslin/about/dolly/facts/life-of-dolly [3] “Dolly and Polly.” Encyclopedia Britannica. Accessed November 26, 2023. https://www.britannica.com/biography/Ian-Wilmut/Dolly-and-Polly [4] Natural World 5 min read. “Dolly the Sheep.” National Museums Scotland. Accessed November 26, 2023.  https://www.nms.ac.uk/explore-our-collections/stories/natural-sciences/dolly-the-sheep/ [5] “Human Cloning.” ScienceDaily. Accessed November 26, 2023. https://www.sciencedaily.com/terms/human_cloning.htm [6] “Somatic Cell Nuclear Transfer.” Somatic_cell_nuclear_transfer. Accessed November 26, 2023. https://www.bionity.com/en/encyclopedia/Somatic_cell_nuclear_transfer.html [7] “Therapeutic Cloning.” Therapeutic Cloning - an overview | ScienceDirect Topics. Accessed November 26, 2023.  https://www.sciencedirect.com/topics/engineering/therapeutic-cloning [8] Watt, Fiona M, and Ryan R Driskell. “The Therapeutic Potential of Stem Cells.” Philosophical transactions of the Royal Society of London. Series B, Biological sciences, January 12, 2010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842697/#:~:text=Almost%20every%20day%20there%20are,%2C%20diabetes%2C%20blindness%20and%20neurodegeneration [9] Ye, Lei, Cory Swingen, and Jianyi Zhang. “Induced Pluripotent Stem Cells and Their Potential for Basic and Clinical Sciences.” Current cardiology reviews, February 1, 2013.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584308/ [10] Ghaedi, Mahboobe, and Laura E Niklason. “Human Pluripotent Stem Cells (Ipsc) Generation, Culture, and Differentiation to Lung Progenitor Cells.” Methods in molecular biology (Clifton, N.J.), 2019.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976544/#:~:text=To%20generate%20the%20iPSCs%2C%20each,low%20as%00.01–0.1%20%25 [11] “Why IPSC Research Is so Important (and so Tough).” Tecan. Accessed November 27, 2023. https://www.tecan.com/blog/why-ipsc-research-is-soimportant#:~:text=For%20example%2C%20iPSC%20are%20used,specific%20cell%20types%20and%20tissues [12] Lowden, Olivia. Advantages and disadvantages of induced pluripotent stem cells, November 10, 2023.  https://blog.bccresearch.com/advantages-and-disadvantages-of-induced-pluripotent-stem-cells [13] “Examining the Ethics of Embryonic Stem Cell Research.” Harvard Stem Cell Institute (HSCI). Accessed November 28, 2023.  https://hsci.harvard.edu/examining-ethics-embryonic-stem-cell-research [14] Lenzer, Jeanne. “Bush Says He Will Veto Stem Cell Funding, despite Vote in Favour in Congress.” BMJ (Clinical research ed.), June 16, 2007.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892464/ [15] Stem cell policy: World stem cell map. (Image: William Hoffman, MBBNet) Accessed November 29, 2023.   https://www.mbbnet.umn.edu/scmap.html [16] Lachmann, P. “Stem Cell Research--Why Is It Regarded as a Threat? An Investigation of the Economic and Ethical Arguments Made against Research with Human Embryonic Stem Cells.” EMBO reports, March 2001.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083849/ [17] Stem cell processing, Cellular and Molecular Therapies - NHS Blood and Transplant. Accessed November 29, 2023. https://www.nhsbt.nhs.uk/cellular-and-molecular-therapies/products-and-services/stem-cell-processing/ [18] Stem Cell Program, Pluripotent Stem Cell Research. Accessed November 29, 2023. https://www.childrenshospital.org/research/programs/stem-cell-program-research/stem-cell-research/pluripotent-stem-cell-research#:~:text=What%20makes%20pluripotent%20stem%20cells,body%20needs%20to%20repair%20itself [19] Beford Research Foundation. ‘What are Induced Pluripotent Stem Cells? (iPS Cells)’ Apr 23, 2011 https://www.youtube.com/watch?v=i-QSurQWZo0 [20] Dana G. ‘Reflecting on the Discovery of the Decade: Induced Pluripotent Stem Cells.’ Accessed November 29, 2023. https://gladstone.org/news/reflecting-discovery-decade-induced-pluripotent-stem-cells ‌[21] Cade Hildreth. Induced Pluripotent Stem Cell (iPS Cell) Applications in 2023. Accessed December 3, 2023. https://bioinformant.com/ips-cell-applications/ [22] Clopton, David. n.d. “Graft versus Host Disease | Radiology Reference Article | Radiopaedia.org .” Radiopaedia.  https://radiopaedia.org/articles/graft-versus-host-disease?lang=gb [23] Dr. Surat, and Dr. Tomislav Mestrovic. Induced Pluripotent Stem (iPS) Cells: Discovery, Advantages and CRISPR Cas9 Gene Editing. Accessed December 3, 2023. https://www.news-medical.net/life-sciences/Induced-Pluripotent-Stem-(iPS)-Cells-Discovery-Advantages-and-CRISPR-Cas9-Gene-Editing.aspx#:~:text=Muhammad%20Khan%20%7C%20TEDxBrentwoodCollegeSchool-,Disadvantages,trigger%20cancer-causing%20gene%20expression [24] First patient receives milestone stem cell-based transplant for Parkinson’s Disease. Feb 28, 2023 https://www.lunduniversity.lu.se/article/first-patient-receives-milestone-stem-cell-based-transplant-parkinsons-disease#:~:text=First%20patient%20receives%20milestone%20stem%20cell-based%20transplant%20for%20Parkinson%27s%20Disease,-Published%2028%20February&text=On%2013th%20of%20February%2C%20a,at%20Skåne%20University%20Hospital%2C%20Sweden . [25] Amanda Morris. Mature ‘lab grown’ neurons hold promise for neurodegenerative disease. Jan 12, 2023 https://news.northwestern.edu/stories/2023/01/mature-lab-grown-neurons-hold-promise-for-neurodegenerative-disease/ [26] University of Nebraska Medical Center. STEM CELLS. Accessed December 5, 2023 https://www.unmc.edu/stemcells/stemcells/unmc.html [27] Michael S. Pepper, C Gouveia. Legislation governing pluripotent stem cells in South Africa. (Image: Melodie Labuschaigne), Sept 2015 https://www.researchgate.net/figure/Somatic-cell-nuclear-transfer-SCNT-SCNT-involves-the-removal-of-the-chromosomes_fig3_285619276

Author : Steffi Kim Brain imaging techniques allow neurologists and researchers alike to measure brain activity, diagnose medical and psychiatric conditions, and gain insight into the brain’s interconnected webs and complex structures. While psychologists once had to rely entirely on observable behavior and could only guess at the workings of the brain, new technologies can reveal the brain’s structure and function in astonishing detail. Each brain scanning technology has specific purposes and limitations. As such, researchers may choose a specific technique or combination of techniques depending on the circumstances and what is being measured. EEG (Electroencephalogram) The EEG was first developed in 1924 by Hans Berger, a German psychiatrist, making it one of the oldest brain imaging technologies. EEG measures the frequency and location of brain waves through a series of small electrodes placed across the scalp. Every time neurons in the brain fire, an electrical field is produced. By measuring electrical activity, the electrodes can effectively assess neuronal firing. The electrodes are commonly attached to a cap and are wired to a monitor that graphs the frequency of brain waves. Different brain waves—gamma, beta, alpha, theta, and delta—signal varying levels of brain alertness and functioning. Abnormal brain wave patterns could be the result of a neurological condition, and EEG is commonly used to test for epilepsy and sleep disorders. fMRI (Functional Magnetic Resonance Imaging) fMRI involves tracking the movement of blood and oxygen through the brain to analyze functioning and structure. Highly active brain regions require more oxygen, and greater blood flow in an area is associated with increased brain activity. To perform an fMRI scan, patients are placed into the tunnel of an MRI scanner, which utilizes strong magnetic fields and radio waves. The magnetic field of the scanner alters the positioning of hydrogen protons in the water of the blood, causing the hydrogen atoms to rotate and release energy. The scanner measures the magnetic signals produced by hydrogen to develop detailed images of the brain. fMRI is widely used in studies, where participants may perform tasks while in the MRI scanner to allow researchers to observe which brain regions are involved. PET (Positron Emission Tomography) PET scans track blood flow in the brain via a radioactive tracer substance. The radioactive substance, which is either injected, swallowed, or inhaled, binds to glucose in the blood. The blood then travels up to the brain and through various regions, emitting gamma waves from positrons in the radioactive tracer interacting with electrons. Neurons utilize glucose as their main energy source, and areas with more glucose indicate higher brain activity. The radioactive substance appears on images in bright, multicolored patches, where red symbolizes the highest level of glucose metabolism and activity, while purple and black represent low levels of function. PET scans, which reveal how well the brain is working on a cellular level, are often used to measure Alzheimer's and seizures, as well as medical conditions. CT (Computerized Tomography) CT scans splice together multiple X-rays to create cross-sectional images or 3D models of the brain. CT scans reveal more information about the brain tissues and skull than typical X-rays and are ideal for assessing fractures, brain injuries, and damage after strokes. References: Bosquez, Taryn. “Neuroimaging: Three Important Brain Imaging Techniques.” ScIU, February 5, 2022. https://blogs.iu.edu/sciu/2022/02/05/three-brain-imaging-techniques/. “Brain Imaging: What Are the Different Types?” BrainLine, April 22, 2011. https://www.brainline.org/slideshow/brain-imaging-what-are-different-types. Genetic Science Learning Center. "Brain Imaging Technologies." Learn.Genetics. June 30, 2015. https://learn.genetics.utah.edu/content/neuroscience/brainimaging/. Lovering, Nancy. “Types of Brain Imaging Techniques.” Psych Central, October 22, 2021. https://psychcentral.com/lib/types-of-brain-imaging-techniques. “Scanning the Brain.” American Psychological Association, August 1, 2014. https://www.apa.org/topics/neuropsychology/brain-form-function.

Author : Steffi Kim It’s a long-established fact that listening to music can affect your feelings and mind. However, only relatively recently has neuroscience allowed these shifts in brain activity to actually be recorded. Music is a universally appreciated art form that, across a vast array of genres, can encompass almost every human experience or feeling. Music is what we turn to for comfort when we feel down; for concentration when studying; or for adrenaline before a sports game. Music has been found to decrease symptoms of depression, anxiety levels, and blood pressure. Moreover, listening to music can boost the immune system as well as improve alertness, memory, and cognitive functioning . How the brain perceives music Essentially, music is a combination of notes, rhythms, melodies, and vocals that the brain absorbs and processes as a song. Sound waves in the air create vibrations in the eardrum that then become electrical signals. The auditory nerve, spanning from the inner ear to the brain stem, encodes the details of the sound and sends it to the temporal lobe to process. The right hemisphere of the temporal lobe interprets the instrumentals and music, while the left hemisphere decodes the language and lyrics. Interestingly, the way the brain processes music is not universal: brain scans have revealed that professional musicians “hear” music differently than others do. Rather than engage the temporal lobe, listening to music causes professional musicians to employ the visual or occipital lobe, indicating that they may be visualizing sheet music or notes while listening. Areas of the brain Music provides a rich, in-the-moment sensory experience that activates almost the entire brain, allowing the neural pathways to be exercised and strengthened. The hypothalamus and autonomic nervous system (ANS) are affected by music, leading to changes in heart rate, sleep, mood, breathing, and other unconscious behaviors. The limbic system, which monitors reward and motivation, becomes active, and dopamine and serotonin are released, boosting happiness and enhancing focus. While music is generally beneficial, it should be noted that listening to intensely sad or angry music can lead to negative emotions and cause the brain to release cortisol. The amygdala, which governs emotions, works in conjunction with the hippocampus to recall emotional memories tied to the music. Listening to music also affects the motor system, which makes dancing or tapping your foot to the beat come naturally. The orbitofrontal cortex (OFC), located in the frontal lobe and implicated in decision-making, displays hyperactivity when listening to music, similar to the hyperactivity the OFC typically displays in people with OCD. An explanation for this is that the tension, anticipation, and resolution of music require high focus and concentration. Furthermore, interpreting lyrics and producing speech engages Broca’s Area and Wernicke’s Area, and, as a result, music may improve language processing. Memory Have you ever recalled one line of an old song, and suddenly remembered the rest of the lyrics? Songs that we listen to repeatedly can become ingrained in our implicit, or unconscious memory. People often listen to the same set of songs from their adolescence and early adulthood, however, listening to unfamiliar music is beneficial because the brain has to adapt and process new sounds. Listening to music from a past time period can help you recall old memories in vivid sensory detail. Remarkably, even though neurodegenerative diseases erode explicit memory, many patients with Alzheimer’s can still recall familiar music and lyrics. Due to muscle memory stored in the cerebellum, patients with neurodegenerative diseases may even remember how to play instruments like the piano. Attaching rhythms and melody to phrases can help the brain recall them more easily—a technique heavily used in commercials. Some studies have found that listening to Mozart while working can enhance spatial processing. Music can also boost memory by triggering neurogenesis, or the formation of neurons, in the hippocampus. Music as therapy and treatment Music has the power to evoke specific emotions and can be used in therapy, specifically in regard to memory and neurodegenerative diseases. By affecting the putamen, rhythms in music can temporarily reduce symptoms of Parkinson’s disease and help patients with coordination and walking. Furthermore, research has suggested that people with epilepsy can minimize the occurrence of seizures by listening to Mozart’s Sonata for Two Pianos in D Major. Overall, more research is needed to fully understand how music affects the brain and to explore possible medical implications. References: Eck, Allison. “How Music Resonates in the Brain.” Harvard Medicine Magazine, April 23, 2024. https://magazine.hms.harvard.edu/articles/how-music-resonates-brain. Heshmat, Shahram. “Why Does Music Evoke Memories?” Psychology Today, September 14, 2021. https://www.psychologytoday.com/us/blog/science-choice/202109/why-does-music-evoke-memories. “Keep Your Brain Young with Music.” Johns Hopkins Medicine, April 13, 2022. https://www.hopkinsmedicine.org/health/wellness-and-prevention/keep-your-brain-young-with-music. Magsamen, Susan. “How Music Affects Your Brain.” Time, April 28, 2023. https://time.com/6275519/how-music-affects-your-brain/. Shepherd, Becks. “How Does Music Affect Your Brain?” LiveScience, December 15, 2022. https://www.livescience.com/how-does-music-affect-your-brain. “Your Brain on Music.” Pegasus Magazine, October 30, 2019. https://www.ucf.edu/pegasus/your-brain-on-music/.

Author: Maia Zaman Arpita Time travel, once thought to be the realm of science fiction has long fascinated scientists and dreamers alike. From H.G. Wells' classic "The Time Machine" to the blockbuster film "Back to the Future," the idea of traveling through time has captured the human imagination. But is time travel really possible? According to the theory of relativity, developed by Albert Einstein in the early 20th century, time is not a constant but is instead relative to an observer. This means that time can move faster or slower for different observers, depending on their speed and the strength of gravity. This has profound implications for time travel, as traveling at high speeds or near massive objects can cause time to pass more slowly or quickly. But does this mean that time travel is possible? Could we one day journey to the past or the future? The answer may lie in a peculiar solution to the theory of relativity: wormholes. Einstein's theory of relativity, specifically the special theory of relativity, changed the way we think about time. According to the theory, time is not a constant but is instead relative to the observer's frame of reference. This means that time can move at different rates for different observers, depending on their speed and the strength of gravity. This strange effect is called "time dilation," and it can have dramatic consequences for time travelers. For example, if a person travels at near the speed of light, time will move more slowly for them than for someone on Earth. This means that when they return to Earth, they will have aged less than the people who stayed behind. This phenomenon has been observed in experiments with atomic clocks, and it is a fundamental part of the way the universe works. But how can we use this knowledge to travel through time? That's where wormholes come in. Wormholes, also known as Einstein-Rosen bridges, are hypothetical tunnels through spacetime that connect two distant points. They are predicted by the mathematics of general relativity, which was developed by Einstein after he formulated the special theory of relativity. In theory, wormholes could allow us to travel vast distances in a short amount of time, by taking a shortcut through space-time. But could they also be used for time travel? A proposed method for time travel using wormholes involves creating a "time machine loop," which could be used to travel to both the future and the past. This method involves creating two wormholes, one in the present and one in the future. The wormhole in the future is then sent back through time to the present, creating a closed loop. By entering the wormhole in the future, a person could emerge back in the present at a later time, traveling to the future. Additionally, the wormhole loop can be further manipulated to allow for travel to the past. By sending the wormhole in the future backward in time, a new closed loop is created that connects the present to the past, allowing a person to travel from the present to the past. This manipulation of the time loop creates a passage between the present and the past, allowing for travel back and forth between the two points in time. While the concept of time travel using wormholes is fascinating, there are several significant challenges and limitations. First, it is not yet known whether wormholes exist in nature. While they are mathematically possible, we have yet to observe any evidence of their existence. Even if they do exist, they are likely to be extremely unstable, making them difficult or impossible to use for travel. Even if we were able to create a wormhole, we would need to find a way to keep it open long enough for a person to travel through it. Another potential issue is the enormous amounts of energy that would be required to create and sustain a wormhole. Moreover, there are a number of theoretical and philosophical questions about the possibility of time travel. For example, what would happen if you were to change something in the past? Could you cause a paradox or would the universe find a way to correct itself? While time travel remains a fascinating subject for scientists, philosophers, and science fiction enthusiasts, it is clear that there are still many challenges and unknowns. Despite these limitations, the pursuit of time travel is an exciting and intellectually stimulating endeavor. It forces us to grapple with fundamental questions about the nature of time, the universe, and our own place within it. As we continue to explore and experiment with the fundamental laws of physics, we may one day discover a way to unlock the secrets of time travel.

Author: Maia Zaman Arpita Introduction In a country known for its lush green forests and rolling rivers, Dr. M. A. Wazed Miah’s expertise in nuclear science and technology has been an illuminating force. His contributions to nuclear energy and peaceful applications of nuclear technology have not only changed the landscape of Bangladesh, but also shone a light on the country’s scientific potential. His work has been pivotial in scientific advancement and in fostering development on Bangladesh's nuclear energy program with a strong emphasis on the peaceful applications of nuclear technology. Dr. Miah’s career is characterized by his commitment to education, research, and international cooperation making him a key figure in the promotion of nuclear science in the developing world. Early life and education Dr. M. A. Wazed Miah who was born on February 7, 1942; in the Bogura district of Bangladesh displayed a keen interest in science at a very young age. His academic journey began at the University of Dhaka, where he pursued a Bachelor of Science degree in Physics. Demonstrating exceptional aptitude, he continued his education at the same institution, obtaining a Master’s degree in Physics. Fueled by a desire to deepen his understanding and to enhance his skills in nuclear science and technology, Dr. Miah moved to the United Kingdom, where he earned a Ph.D. in Nuclear Physics from the University of London. His doctoral research focused on nuclear interactions which served as a cornerstone for his future contributions to the field. Contributions to Nuclear Science Dr. Wazed Miah's career is marked by extensive research in nuclear physics and a steadfast commitment to the peaceful utilization of nuclear technology. In 1973, he played a crucial role in the establishment of the Bangladesh Atomic Energy Commission (BAEC), serving as its first chairman. Under his leadership, the commission focused on harnessing nuclear energy for peaceful applications, including advancements in agriculture, medicine, and energy production. His expertise in nuclear reactor technology and radiation protection has been instrumental in ensuring the safe implementation of nuclear energy initiatives in Bangladesh. Dr. Miah was actively involved in the development and commissioning of the country's first research reactor, which has been pivotal for scientific research and training. Additionally, he has contributed significantly to the establishment of nuclear safety protocols and regulatory frameworks, ensuring that the country's nuclear activities align with international safety standards. Dr. Miah has also been a prolific contributor to scientific literature, authoring numerous research papers and articles that address various aspects of nuclear science. His work has been published in reputable scientific journals, contributing to the global discourse on nuclear technology and its applications. Advocacy for peaceful nuclear technology Throughout his career, Dr. Wazed Miah has been an ardent advocate for the peaceful applications of nuclear energy. He consistently emphasized on the critical role of nuclear technology in addressing the energy demands of developing nations, particularly in the context of sustainable development. His efforts have been directed toward promoting nuclear science education and research, thereby nurturing a new generation of scientists and engineers in Bangladesh. Dr. Miah has been involved in various educational initiatives, collaborating with universities and research institutions to enhance nuclear science curricula and to provide training opportunities for students and professionals. His commitment to education extends beyond the classroom; he has organized workshops, seminars, and conferences aimed at raising awareness about the benefits and safety of nuclear technology. Moreover, Dr. Miah has been a strong proponent of international collaboration in nuclear research and safety. He has represented Bangladesh in numerous international forums, including the International Atomic Energy Agency (IAEA), where he participated in discussions on nuclear safety, security, and the peaceful use of nuclear energy. His engagement in these forums has facilitated knowledge exchange and has positioned Bangladesh as an emerging player in the global nuclear community. Conclusion Dr. M. A. Wazed Miah is a distinguished figure in the field of nuclear science, whose dedication and contributions have significantly influenced the trajectory of nuclear technology in Bangladesh. His advocacy for the peaceful use of nuclear energy continues to guide and inspire future generations of scientists and policymakers. As Bangladesh progresses towards a sustainable energy future, the principles and vision articulated by Dr. Wazed Miah remain essential in shaping the responsible development of nuclear technology. His life and work exemplify the potential of science to contribute to societal advancement, making him a vital figure in the ongoing discourse on nuclear energy and its role in global development.

Authors: Aditya Tyagi, Rushdanya Bushra, and Deniz Tiryakioglu Abstract: Known as the "brain-eating amoeba," Naegleria fowleri is a thermophilic, free-living protozoan that causes primary amoebic meningoencephalitis (PAM), an infection of the central nervous system that is uncommon but nearly always fatal. This review looks at the pathophysiology, difficulties with diagnosis, and approaches to treating infections caused by N. fowleri. The pathogenesis starts when the amoeba's trophozoite form enters the nasal passages, usually as a result of exposure to freshwater. It then migrates down the olfactory nerve and infiltrates the brain, resulting in extensive and fast neuroinflammation as well as necrosis. The early symptoms of PAM are nonspecific and mirror bacterial meningitis, making clinical identification difficult and raising suspicion in endemic locations. Cerebrospinal fluid (CSF) examination is necessary for diagnostic confirmation; the presence of motile trophozoites or positive PCR results indicate infection. There are few and frequently ineffective treatment options available; however, a combination therapy using amphotericin B, rifampin, and miltefosine has demonstrated some success. Aggressive treatment and early diagnosis are still essential for patient survival. In order to tackle this fatal infection, this systematic review emphasizes the need for increased awareness, quick diagnosis methods, and innovative therapy options.   Diagnosis: The primary methods for diagnosing Naegleria fowleri are imaging scans, laboratory testing, and clinical suspicion. A lumbar puncture is usually done to acquire cerebrospinal fluid (CSF) for investigation when PAM is suspected. Low glucose, high protein levels, and an increased white blood cell count (pleocytosis) are common findings in the CSF of patients infected with Naegleria fowleri. These findings are also suggestive of bacterial meningitis. However, to identify the amoeba itself, particular diagnostic procedures are required. Detection of Naegleria fowleri in Patients: Several laboratory methods can be used to identify Naegleria fowleri in patients. Motile amoebae can be directly detected by direct microscopic analysis of the CSF under a microscope, although this technique needs a trained technician and is not always conclusive. A variety of staining methods, including trichrome or Giemsa-Wright, can improve the amoebae's appearance in CSF samples. Polymerase chain reaction (PCR) and immunofluorescence assays are examples of more sophisticated techniques. Naegleria fowleri DNA can be found in CSF samples using PCR, a very sensitive method that offers a conclusive diagnosis. Through the use of fluorescent dye-tagged antibodies that bind to Naegleria fowleri specifically, immunofluorescence assays enable the detection of the organism under a fluorescence microscope. Even though these techniques are more precise, not all healthcare facilities may be able to use them because they need certain tools and skilled workers. Imaging tests like magnetic resonance imaging (MRI) and computed tomography (CT) scans can aid in the diagnosis in addition to CSF analysis by identifying brain abnormalities that are consistent with PAM. These could include enlargement of the brain and other indicators of severe inflammation. Initiating proper treatment for Naegleria fowleri requires early and precise detection. This treatment may involve a combination of antimicrobial medicines and supportive care measures. The prognosis for PAM is still poor despite these efforts, which emphasizes the significance of prompt identification and treatment. Treatment: Due to the rarity of human infections, case reports and in vitro research mostly inform treatment choices for N. fowleri infections. Based on this research, amphotericin B is generally regarded as the most effective medicine, despite the paucity of clinical trials evaluating therapeutic efficacy. Furthermore, case reports have included the use of additional anti-infectives, though their effectiveness may vary, such as azithromycin, rifampin, miltefosine, miconazole, and fluconazole. Other agents, such as hygromycin, roxithromycin, clarithromycin, erythromycin, roxithromycin, and zeocin, have also been examined in vitro and/or in vivo. Nevertheless, more research is needed to fully understand their clinical usefulness and effectiveness in treating N. fowleri infections. Amphotericin B In a recent study, a total of 381 global cases of PAM were identified from 1937 through 2018, and only seven survivors were reported. (Debnath 2) From 1937 to 2013, there were 142 reported cases of PAM in the United States. Treatment data for 70 of the 142 (49%) patients were available. Among these patients, 36 (51%) received treatment for PAM, and 3 (8%) of them survived. All 36 patients treated for PAM were administered amphotericin B, with 7 (19%) receiving only intravenous (IV) therapy, 5 (14%) receiving only intrathecal (IT) therapy, and 24 (67%) receiving a combination of IV and IT therapy. Additionally, 7 patients received a non-deoxycholate amphotericin B formulation, which includes liposomal and lipid complex formulations. The original US survivor and the 2013 survivors received deoxycholate amphotericin B. AmBisome, the liposomal formulation of amphotericin B, was approved for use in the United States in 1997 by the US Food and Drug Administration. Patients treated with amphotericin B for Naegleria after 1997 were more likely to receive the liposomal preparation, as fewer renal adverse effects have been reported with this formulation. However, it has been found that liposomal amphotericin B is less effective against N. fowleri in vitro and in a mouse model compared to deoxycholate amphotericin B. It's important to note that these findings came from two different studies, and the deoxycholate formulation was given at a higher dose than what is typically used in patients. Seven patients with N. fowleri infection received a non-deoxycholate formulation. Given the extremely poor prognosis of PAM caused by N. fowleri, healthcare providers might want to consider using deoxycholate amphotericin B instead of the liposomal or lipid complex formulation. However, if deoxycholate amphotericin B is not immediately available, treatment should be initiated with a non-deoxycholate formulation to facilitate prompt treatment of the patient. Treatment history of seven confirmed survivors showed that all survivors received amphotericin B, either intravenously or both intravenously and intrathecally. Only one survivor received amphotericin B alone; the rest of the survivors were treated with a combination of drugs. (Debnath 2) Unfortunately, amphotericin B alone is not universally effective. It was administered to nearly three-quarters (71%) of PAM patients. The formulation of amphotericin B (e.g., deoxycholate vs. lipid or liposomal) may play a role in treatment effectiveness. Conventional deoxycholate formulations have shown greater efficacy in vitro and in mouse models, despite greater adverse effects. Additionally, amphotericin B and the other drugs included in survivors’ regimens may not be available in all settings. Multiple case reports specifically mentioned unavailability of amphotericin B at the time of patient presentation and diagnosis.(Gharpure et al. 7) The repurposing of antifungal drugs in the drug discovery of Primary Amebic Meningoencephalitis (PAM) has a historical context. Amphotericin B, an antifungal drug, was used in all confirmed survivors and administered to about three-quarters of PAM patients. However, it was not universally effective. (Debnath 5)As a result, researchers investigated the effect of other antifungal drugs to identify a more active and less toxic alternative to amphotericin B. A water-soluble polyene macrolide called corifungin, which is in the same class as amphotericin B, was tested against N. fowleri trophozoites. The compound was found to be twice as potent as amphotericin B. Although in vitro studies suggested that corifungin may have a similar mechanism of action to amphotericin B in N. fowleri, the increased solubility of corifungin may have contributed to its better tolerability and pharmacokinetic distribution in animals. (Debnath 4) Silver nanoparticles were conjugated with amphotericin B, resulting in enhanced amebicidal activity. Additional studies are needed to confirm whether this increased activity observed in vitro translates to improved drug delivery and efficacy in animal models. (Debnath 4) Miltefosine In 1980, the drug miltefosine was first used as an experimental treatment for breast cancer. It has been observed that the Naegleria parasite can cause a strong inflammatory response, resulting in tissue damage and bleeding. By 2013, the CDC had reported 26 cases where miltefosine was used. In a laboratory study, miltefosine was compared with amphotericin B over the course of a month. The study found that the minimum amount of the drug needed to inhibit the growth of the parasite was 0.25 ug/ml for miltefosine and 0.78 ug/ml for amphotericin B. The survival rates for patients treated with miltefosine were 55%, compared to 40% for those treated with amphotericin B. The optimal dosage, frequency, and treatment duration for miltefosine are not yet fully understood, but a common recommendation is to not exceed 50 mg tablets and a maximum daily dosage of 2.5 mg/kg. The duration of treatment varies depending on the individual case. In 2013, two children survived and recovered from primary amoebic meningoencephalitis after being treated with miltefosine. In 2016, another child became the fourth person in the United States to survive Naegleria fowleri infection after receiving treatment that included miltefosine. In 2013, during the summer, a 12-year-old girl from Arkansas was successfully treated with a drug called Miltefisine for PAM, leading to full neurological recovery. The treatment also involved the administration of MLT, AmB, FCZ, AZM, RIF, and Dexamethasone (DEX). In addition, the girl was put into a hypothermic state to manage intracranial pressure and reduce brain injury caused by hyperinflammation. The treatment regimen used in a 12-year-old girl was later administered to two other patients, a 12-year-old boy and an 8-year-old boy. One of them survived but experienced poor neurological function, including static encephalopathy, profound mental disability, and partial seizure disorder control with anticonvulsant therapy. The other patient unfortunately did not survive and was declared brain-dead on hospital day 16 due to brain herniation. Her treatment plan included all the medications administered to the two patients. Notable distinctions in her medical progress and treatment compared to the two patients mentioned here involved receiving Naegleria-specific drugs about 48 hours after symptoms appeared and undergoing intensive management of increased pressure inside the skull, which included therapeutic hypothermia. The three patients discussed in this report all received miltefosine as part of their treatment for Naegleria infection, but their outcomes varied widely. One patient died, another survived with significant neurological impairment, and the third survived with full neurological recovery. This shows that while miltefosine shows promise as a treatment for Naegleria infection, it is not a guaranteed cure. Since 2013, all surviving US patients with Naegleria infection received miltefosine, compared to only a third of fatal cases. Successful treatment of Naegleria infection likely involves early diagnosis, combination drug therapy (including miltefosine), and aggressive management of elevated intracranial pressure, similar to the approach used in treating traumatic brain injury. Azithromycin Although amphotericin B is the first choice for treating primary amebic meningoencephalitis, it is often associated with renal toxicity, leading to azotemia and hypokalemia. Furthermore, not all patients treated with amphotericin B have survived primary amebic meningoencephalitis. In a study, researchers found that azithromycin, a macrolide antibiotic, was chosen for the study based on previous reports describing the in vitro sensitivity of Acanthamoeba spp. to this drug and its activity in experimental toxoplasmosis. The researchers discovered that azithromycin was highly active against N. fowleri in vitro and that it protected 100% of mice infected with N. fowleri at a dose of 75mg/kg of body weight per day for 5 days. In contrast, amphotericin B only protected 50% of mice at a dose of 7.5 mg/kg per day, while all control mice died during the 28-day observation period. As azithromycin is a relatively non-toxic agent that might be useful in treating PAM alone or in combination with amphotericin B, the researchers evaluated the combined activity of azithromycin and amphotericin B in vitro and in vivo. In this study, it was discovered that the combination of amphotericin B and azithromycin had a synergistic effect against N. fowleri when used together in fixed concentration ratios of 1:1, 1:3, and 3:1. The study also investigated the combined effect of these two drugs in a mouse model of PAM. It was found that a combination of 2.5 mg/kg of amphotericin B and 25 mg/kg of azithromycin, administered once daily for 5 days, provided 100% protection to mice infected with N. fowleri. In comparison, when used individually, amphotericin B and azithromycin only protected 27% and 40% of mice, respectively. These findings suggest that the combined use of these agents was 100% effective, while each agent alone was less than 50% effective, consistent with the observed synergy in vitro. There is little known about the mechanism of action of azithromycin against N. fowleri. Azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking peptide bond formation and translocation. Azithromycin has been shown to be widely distributed in brain tissue following systemic administration in humans, whereas amphotericin B exhibits poor penetration of the blood-brain barrier. N. fowleri exposed to amphotericin B rounds up and fails to form pseudopodia. The ultrastructural abnormalities included alteration of nuclear shape, degeneration of mitochondria, and the appearance of autophagic vacuoles. The current study shows that azithromycin and amphotericin B have a synergistic effect against the Lee strain of N. fowleri. This suggests that using these two agents together could be an effective treatment for human infections with this organism. Further research should be done to determine the exact range of synergistic activity of these two agents, and additional studies with other agents could be conducted to improve the selection of drugs and the treatment of N. fowleri infection. Rifampin Although rifampin has been used in all of the PAM survivor cases in the United States and Mexico (all three cases in the United States and one survivor in Mexico), its efficacy remains questionable. The main issue is whether enough rifampin enters the central nervous system (CNS) at standard therapeutic doses. Several studies have shown that rifampin reaches favorable concentrations in the CNS, as measured by drug concentrations in the cerebrospinal fluid (CSF). However, a report by Mindermann et al. found significant variations in the concentrations of rifampin in different parts of the CNS. Concentrations in the cerebral extracellular space and in normal brain tissue were measured at 0.32 ± 0.11 μg/ml and 0.29 ± 0.15 μg/ml, respectively. These concentrations would be sufficient to exceed the required minimum inhibitory concentration (MIC) for most susceptible bacteria but might not be enough to eradicate N. fowleri. In an initial report by Thong et al. in 1977, it was found that the natural product rifamycin delayed the growth of N. fowleri by 30 to 35% when used at concentrations of 10 μg/ml over a 3-day period. However, rifamycin lost its ability to inhibit N. fowleri growth by the 6th day of incubation. It was observed that growth inhibition (>80%) was sustained for the entire 6-day period only when higher concentrations of rifampin, a semisynthetic analogue of rifamycin (100 μg/ml), were used. The later report by Ondarza did not show any minimum inhibitory concentration (MIC) for rifampin against N. fowleri. It revealed a 50% inhibitory concentration (IC50) of >32 μg/ml, which was the highest concentration tested in the study. These findings do not provide evidence to support the use of standard doses of rifampin for treating PAM. One issue with using rifampin to treat N. fowleri is the high potential for drug-drug interactions when combined with other medications. Rifampin is known to induce the CYP2 and CYP3 family of monooxygenase enzymes, specifically CYP2C9, CYP2C19, and CYP3A4. The greatest likelihood for interaction with rifampin is when it is used with 14α-demethylase inhibitors, also known as the azole fungistatics. In most cases, miconazole was initially used before switching to fluconazole in more recent cases. 14α-Demethylase is a specific isoform, and there are known interactions between rifampin and fluconazole. When these two drugs are taken together, it leads to significant changes in the way fluconazole is processed in the body: a decrease of more than 20% in the area under the concentration-time curve (AUC), up to a 50% decrease in critically ill patients, at least a 30% increase in clearance rate, and a 28% shorter half-life. Since there has been a demonstrated synergy between 14α-demethylase inhibitors and amphotericin B against N.fowleri, adding rifampin to the combination may not be very beneficial and could actually work against the maximum therapeutic effect of the other agents. Fluconazole In certain instances of Naegleria fowleri infection, amphotericin B has been used with the azole antifungal medication fluconazole for therapy. Studies show that some patients benefit further from fluconazole added to amphotericin B medication.Fluconazole may be more effective than amphotericin B because it reaches the central nervous system (CNS) more profoundly. Fluconazole and amphotericin B have synergistic actions that help to eradicate N. fowleri infection, presumably as a result of neutrophil recruitment. As a result, fluconazole can be used as an addition to amphotericin B in individuals suspected of having N. fowleri.The CDC advises administering intravenous fluconazole once day at a dose of 10 mg/kg/day, up to a maximum of 600 mg/day, for a total of 28 days. The goal of this dosage schedule is to maximize fluconazole's therapeutic efficacy in N. fowleri infections.Another azole antifungal that works well against N. fowleri in vitro is voriconazole, which is effective at doses of at least 1 μg/ml. Specifically, fluconazole has been combined with additional medications, including rifampin, miltefosine, and amphotericin B, to develop a multimodal therapy plan. In addition to fluconazole's inhibition of ergosterol synthesis, amphotericin B works by binding to ergosterol and creating holes in the cell membrane. The medicine miltefosine, which was first created as an anti-leishmanial medication, has demonstrated amoebicidal activity, which increases the efficacy of the treatment plan. Clinical instances have shown that combined therapy can provide better results than monotherapy, but because PAM progresses aggressively and is difficult to diagnose in a timely manner, survival rates are still low. A further difficulty is the blood-brain barrier, which restricts the amount of medication that can reach the infection site. To enhance azoles' and other therapeutic agents' penetration of the central nervous system, research is still being done on dose regimens and drug delivery techniques. Despite these challenges, azoles remain a crucial component in the therapeutic arsenal against brain-eating amoebas. Ongoing research and clinical trials are essential to refine treatment protocols and enhance the efficacy of these drugs, offering hope for improved survival rates in affected patients. Early diagnosis and prompt initiation of combination therapy are vital, emphasizing the need for heightened awareness and rapid medical response to symptoms indicative of PAM. Vaccination as a Potential Treatment Strategy: Vaccines play a crucial role in the treatment strategies for all diseases, including infections caused by Naegleria fowleri. However, despite recent efforts, a universally accepted and officially authorized vaccination for Naegleria fowleri remains undiscovered. This section will address and discuss potential candidate proteins for an innovative method of treating this lethal infection. In a recent study, Gutiérrez-Sánchez et al. (2023) investigated the role of two potential antigen vaccine candidates, a 19 kDA polypeptide and a MP2CL5 peptide, using a BALB/c mouse model (Gutiérrez-Sánchez, 2023). They measured the immunologic response using different methods; including flow cytometry, ELISA, and the investigation of specific antibodies (IgA, IgG, and IgM) in the serum and nasal cavity. According to the results, the use of 19-kDa polypeptide yielded promising results, with a 80% protection rate against Naegleria fowleri infection. In addition, when combined with cholera toxin (CT), this vaccine candidate demonstrated up to 100% protection. Although both antigens showed a specific immune response against infection, a noteworthy increase in the number of T and B lymphocytes was observed by the team in nasal passages and nasal-associated lymphoid tissue. Finally, increased levels of IgA, IgG, and IgM in vaccinated mice were detected, both in the serum and nasal cavity. These findings highlight the potential of these antigens as a promising candidate for a vaccine against Naegleria fowleri infections due to their high efficacy and capacity to offer localized protection. Another separate study was conducted to assess the immunological effects of an mRNA-based vaccination for the treatment of PAM by Naveed and his team using a BALB/c mouse model (Naveed, Muhammad, et al., 2024). They analyzed the responses by measuring T-cell numbers and using IgA and IgG antibody levels in various samples, including mucosal tissue and serum. In this study, increased antibody levels were detected in both samples, suggesting a systemic response against Naegleria fowleri antigens. Moreover, the production of important cytokines such as IFN-γ were also observed. This highlights the enhanced T-cell responses in the mice model. This holds significance since it implies a strong immune response. The group also stated no side or adverse effects on the model during or after the trials, impling its safety. Despite the promising results, more clinical and preclinical trials are needed to decide whether mRNA vaccines hold a potential to treat PAM in patients (Naveed, Muhammad, et al., 2024). Immunoinformatics is another popular technique used by many researchers to develop vaccines in a safer way. In 2023, Sarfraz et al. demonstrated the use of this innovative method to develop a preventative approach for PAM infections. The objective of this study was to find distinct T- and B-cell epitopes through the utilization of diverse screening techniques. Different parameters including cytokine-inductivity, allergenicity, toxicity, antigenicity were taken into account to find epitopes that trigger the immune responses of both cell types (Sarfraz, Asifa, et al., 2023). Although further research and the support of more clinical studies are needed to fully demonstrate its efficacy on patients suffering from PAM infections, a multi-epitope vaccine from the most-identified epitopes of B- and T-cells was constructed as a result of this study. This emphasizes the importance of employing computational techniques in vaccine design, utilizing a fast and efficient method (Sarfraz, Asifa, et al., 2023). Vaccines are a crucial component of therapy strategies. Although there is a dearth of research on vaccine development for Naegleria fowleri infections, multiple studies have consistently shown encouraging and thus promising outcomes. This serves as a reminder that conducting additional study can lead to the identification of more antibodies, which can be advantageous in the treatment of this lethal disease. Conclusion: Naegleria fowleri, often referred to as the "brain-eating amoeba," remains a formidable pathogen due to its rapid pathogenesis and the high fatality rate associated with primary amoebic meningoencephalitis (PAM). This review highlights the critical challenges in diagnosing and treating infections caused by N. fowleri, emphasizing the need for heightened awareness and advanced diagnostic methods to facilitate early detection. The pathogenesis involves the amoeba entering the nasal passages and migrating to the brain, causing extensive neuroinflammation and necrosis. The diagnostic process is complicated by the nonspecific early symptoms of PAM, which mimic bacterial meningitis, necessitating specific cerebrospinal fluid (CSF) examination and advanced laboratory techniques like PCR and immunofluorescence assays. Treatment strategies, though limited, have shown some promise. Amphotericin B remains the cornerstone of therapy, though its efficacy varies, and it is often accompanied by significant adverse effects. Combination therapies, including miltefosine, azithromycin, rifampin, and fluconazole, have shown synergistic effects and improved outcomes in some cases, but these treatments are not universally effective and are often hindered by issues such as drug availability and the ability to penetrate the blood-brain barrier. Moreover, the exploration of innovative treatment strategies, such as vaccine development, presents a promising frontier in combating N. fowleri infections. Studies investigating potential vaccine candidates, such as the 19 kDa polypeptide, MP2CL5 peptide, and mRNA-based vaccines, have shown encouraging results in animal models, highlighting their potential to offer localized and systemic protection against N. fowleri. Immunoinformatics approaches further underscore the potential for developing multi-epitope vaccines, utilizing computational techniques to identify effective T- and B-cell epitopes. In conclusion, while significant progress has been made in understanding the pathogenesis, diagnosis, and treatment of N. fowleri infections, challenges remain. Early and precise diagnosis, aggressive and combination treatment strategies, and innovative approaches like vaccine development are essential to improving patient outcomes. Continued research and clinical trials are crucial to refining these strategies and enhancing the efficacy of treatments, offering hope for better survival rates in the face of this lethal infection. References 1. Gutiérrez-Sánchez, Mara, et al. “Two MP2CL5 Antigen Vaccines from Naegleria Fowleri Stimulate the Immune Response against Meningitis in the BALB/C Model.” Infection and Immunity, U.S. National Library of Medicine, July 2023, www.ncbi.nlm.nih.gov/pmc/articles/pmid/37272791/. Accessed 02 June 2024. 2. Naveed, Muhammad, et al. “Development and Immunological Evaluation of an Mrna-Based Vaccine Targeting Naegleria Fowleri for the Treatment of Primary Amoebic Meningoencephalitis.” Nature News, Nature Publishing Group, 8 Jan. 2024, www.nature.com/articles/s41598-023-51127-8. Accessed 02 June 2024. 3. Sarfraz, Asifa, et al. “Structural Informatics Approach for Designing an Epitope-Based Vaccine against the Brain-Eating Naegleria Fowleri.” Frontiers, 16 Oct. 2023, www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1284621/full. Accessed 02 June 2024. 4. Gharpure, Radhika, et al. "Epidemiology and clinical characteristics of primary amebic meningoencephalitis caused by Naegleria fowleri: a global review." Clinical Infectious Diseases 73.1 (2021): e19-e27. 5. Debnath, Anjan. "Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads." Expert review of anti-infective therapy 19.9 (2021): 1099-1106. 6. Capewell, Linda G., et al. "Diagnosis, clinical course, and treatment of primary amoebic meningoencephalitis in the United States, 1937–2013." Journal of the Pediatric Infectious Diseases Society 4.4 (2015): e68-e75. 7. Alli, Ammar, et al. "Miltefosine: a miracle drug for meningoencephalitis caused by free-living amoebas." Cureus 13.3 (2021). 8. Güémez, Andrea, and Elisa García. "Primary amoebic meningoencephalitis by Naegleria fowleri: pathogenesis and treatments." Biomolecules 11.9 (2021): 1320. 9. Cope, Jennifer R., et al. "Use of the novel therapeutic agent miltefosine for the treatment of primary amebic meningoencephalitis: report of 1 fatal and 1 surviving case." Clinical Infectious Diseases 62.6 (2016): 774-776. 10. Soltow, Shannon M., and George M. Brenner. "Synergistic activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis." Antimicrobial agents and chemotherapy 51.1 (2007): 23-27. 11. Goswick, Shannon M., and George M. Brenner. "Activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis." Antimicrobial agents and chemotherapy 47.2 (2003): 524-528. 12. Grace, Eddie, Scott Asbill, and Kris Virga. "Naegleria fowleri: pathogenesis, diagnosis, and treatment options." Antimicrobial agents and chemotherapy 59.11 (2015): 6677-6681. Author Biographies Aditya Tyagi, a rising junior, is passionately pursuing a career as a neurosurgeon. With a deep interest in the medical field, Aditya aims to impact people's lives positively through science and research. His commitment to understanding the human body and finding innovative medical solutions drives his dedication to becoming a neurosurgeon. Aditya is determined to make a meaningful difference in patients' lives through his future work in medicine. Rushdanya Bushra is currently a student at Govt. Hazi Muhammad Mohsin College. From a very young age, Rushdanya has had a keen interest in biology. Rushdanya always longed to delve deeply into this subject, and over time, his interest developed into a habit. He never get bored reading anything related to this field. His interest deepened when Rushdanya began looking through his aunt’s medical books and research works, sparking his own desire to pursue this type of research. Now Rushdanya wants to pursue my higher education in a biology-related subject so that he can engage with his passion. Rushdanya wants to gain a deeper understanding of the mechanisms of living organisms and learn about diseases and their treatments. Deniz is a passionate 17-year-old high school student from Turkey with a dream of becoming a neurologist specializing in neurodegenerative diseases, particularly Parkinson’s. She spends her free time reading books and playing volleyball. Inspired by a fascination with the complexities of the brain, she is dedicated to understanding and someday treating Parkinson’s disease. Her academic pursuits are driven by a desire to contribute meaningfully to neuroscience, aiming to make a difference in the lives of those affected by neurological conditions.

Author: Jaxon Pang Abstract Nanotechnology allows for the development and implementation of medicinal usage to operate on the nanoscale. Also being referred to nanomedicine in this field, the application of nanotechnology towards medicinal research has been a result of technological advancements throughout the years which have allowed scientists to develop and improve methods of dealing with various illnesses and diseases. However, recent research has also demonstrated instances of particle toxicity, known as nanotoxicology, stirring concern regarding the clinical use of nanotechnology, causing harm to both hosts and the surrounding environment. This paper will aim to deliver the aspects of nanomedicine with the potential of treating severe illnesses whilst also providing insight into their impacts on the same people and the wider world, and most importantly how some of these social and environmental issues could be potentially solved. 1.0 Introduction and History The rapidly developing world of the 21st century provides an extensive array of resources in biological and chemical engineering. With this, scientists and researchers have been able to further develop nanotechnology to accommodate the growing difficulty in diagnosing and treating various resistant or incurable diseases. However, the birth of nanotechnology really dated back to 1959, from American physicist and Nobel Prize laureate Richard Feynman, who introduced the concept of nanotechnology at the annual meeting of the American Physical Society, hosted at the California Institute of Technology, where he presented a lecture titled “There’s Plenty of Room at the Bottom”. He described a vision of using machines to construct smaller machines down to the molecular level, where his hypotheses were eventually proven correct, considering him to be the father of modern nanotechnology. 15 years later, Norio Taniguchi, a Japanese scientist, was the first to use and define the term “nanotechnology” in 1974, being that “nanotechnology mainly consists of the processing of separation, consolidation, and deformation of materials by one atom or one molecule”. After this discovery, two manufacturing approaches have been developed to interpret the synthesis of these nanostructures: Top-down and Bottom-up, both differing in speed, quality, and cost. The Top-down approach involved the breaking down of material into nano sized material, whilst the Bottom-up approach referred to the buildup of nanostructures from its basis using chemical and physical methods, atom by atom. These concepts essentially formed the fundamental aspects of nanoscience applications and allowed the idea of the build-up of complex machines from individual atoms which can independently manipulate molecules and atoms to produce self-assembly nanostructures, to become a reality. Recent studies in recent years have highlighted how the implementation of nanotechnology into biomedicine has shown great potential. Examples included using nanoparticles to help with the diagnosis of many human diseases, and even drug delivery and molecular imaging. These achievements via intensive research yielded great results. Remarkably, many medical related products containing nanomaterials are on the market in the United States. These are usually categorised under “nanopharmaceuticals”, which include nanomaterials with the purpose of drug delivery and regenerative medicine. More developed types of nanoparticles included covering antibacterial activities as well. Progress has also been made in the field of nano-oncology. By improving the efficacy of traditional chemotherapy drugs targeting a range of aggressive human cancers, researchers have successfully achieved in targeting the tumour site with several functional molecules such as nanoparticles, antibodies and cytotoxic agents. In this case, studies have shown how nanomaterials can be employed itself to deliver therapeutic molecules to regulate and control essential biological processes such as autophagy, metabolism, anticancer activity, and oxidative stress.1 However, implementing nanoparticles into medicine do have its own set of drawbacks. Due to their specific properties, such as their increased surface area, it results in increased reactivity and biological activity, meaning that there is an increased chance that contact with nanoparticles may cause permanent damage to the central nervous system.2 It is suggested that toxicities are inversely proportional to the size of the nanoparticles, thus nanoparticles in general are more toxic to human health in comparison to larger sized particles of the same chemical substance.3 This makes the risk of infusing nanoparticles into human health greater as while they cause similar effects from other foreign particles injected into a human, such as inflammation or lung cancer, they may be more potent due to their greater surface area.4 All in all, with the huge imbalance between the advantages and disadvantages of incorporating nanotechnology into humans for medicinal applications, it begs the question of whether nanoparticles should really be used in the field of medicine, and the pros and cons from both points of view. 2.0 Background 2.1 The increased incorporation of nanotechnology into medicine In essence, the utilisation of nanodevices can be used in diagnostics for early and rapid disease identification for immediate medical procedural recommendations. Using nanoparticles to assist in medical diagnosis means that various, undetectable diseases could be discerned as early as possible, and the appropriate medication could be administered to treat the disease before it gets too serious. Even if the detected illness has no effective treatment yet, researchers can use the nanoparticles to test and analyse the disease to conjure a temporary cure, if not a permanent one. Due to its molecular scale, nanotechnology has the potential to revolutionise the field of healthcare diagnostics due to its improved accuracy, sensitivity, and speed of medical tests compared to other diagnostic medical equipment. The needs and applications of nanomaterials in many areas of human endeavours such as industry, agriculture, business, medicine and public health have skyrocketed its popularity. Between 1997 and 2005, investment in nanotechnology research and development by governments around the world soared from $432 million to about $4.1 billion, and the corresponding industry investment exceeded that of the government’s investment by 2005. By 2015, products incorporating nanotechnology contributed to approximately $1 trillion to the global economy, as depicted in Figure 1 by Lux Research: (Figure 1)5 About two million workers will be employed in nanotechnology industries, and three times that many will have supporting jobs in the future, as predicted by Lux Research.6 The drive for technological development fuels this idea of increased usage of nanoparticles. For example, diagnostic imaging provides a visual interpretation of the interior of an organism, such as organs or tissues. Utilising nanoparticles in diagnostic imaging allows for the enhancement of imaging modalities such as MRIs or computerised tomography scans, making them a lot clearer and accurate. Using nanoparticles can also incorporate the detection of life-threatening diseases such as various cancers quickly at an earlier state to enable timely treatment and prevention. In addition, other biosensors using nanoparticles have been developed which can detect low levels of biomolecules in fluids such as in blood or in urine, once again leading to the facilitating of early detection and management. Similar dimensional applications have been used in the form of nanofluidic devices to isolate and analyse specific cells, proteins, and genetic material to provide rapid and accurate diagnosis of diseases. Recently, an increase in the association between nanotechnology and drug deliveries have been evident, through various technologies and systems. This correlates with gene therapy. By incorporating nanotechnology into drug delivery, researchers have been able to enable effective and targeted drug delivery with minimal side effects, increasing the therapeutic efficacy of the drugs. Furthermore, by using DNA-based drug delivery, which are drug delivery devices recently introduced, such as DNA guns and DNA vaccines, it also enhances drug delivery by specifically delivering drugs to the target site and reducing the toxicity associated, while simultaneously protecting the DNA molecules from degrading, modifying DNA sequences and correcting genetic mutations to increase the efficiency and safety of gene therapy as well. In short, with the development of technology in the field of medicine, researchers have taken massive steps in these discoveries to their advantage to produce and research further into nanomedicine to find ways to continue diagnosing and treating diseases. Progress is aiming for maximum efficacy while simultaneously causing minimal side effects and potential harm towards the recipients.7 2.2 Impacts of nanomedicine in humans Primarily, people have been exposed to various nano-scale materials since childhood, and this new, emerging field of nanotechnology has become another potential threat to human life. Due to their small size, it is much easier for nanoparticles to enter the human body and cross the various biological barriers, hence the possibility of them reaching the most sensitive organs. Scientists have proposed that nanoparticles of size less than 10 nm would act like a gas and can enter human tissues easily, likely to disrupt the cell normal biochemical environment. Animals and human studies have shown that after inhalation, and through oral exposure, nanoparticles are distributed to the liver, heart, spleen, and brains well as to the lungs and gastrointestinal tract. To clear these nanoparticles from the body, components of the immune system are activated, yet research shows that the estimated half-life of nanoparticles in human lungs is about 700 days, posing a consistent threat to the respiratory system. During metabolism, some of the nanoparticles are congregated in the liver tissues. They are more toxic to human health in comparison to larger sized particles of the same chemical substance, and it is usually suggested that toxicities are inversely proportional to the size of the nanoparticles. Due to their physicochemical properties in different biological systems, unpredictable health outcomes of these nanoparticles were eminent to scientists.8 In general, properties such as absorption, distribution, metabolism, and clearance contribute to their toxicological profile in biological systems. Toxicological concerns means that size, shape, surface area, and chemical compounds need to be considered during the manufacture of these nanoparticles, as they can exert mechanisms of cytotoxicity that interfere with cellular homeostasis. The toxicity of nanoparticles also depends on the chemical components on their surfaces. Some metal oxides, such as zinc oxide (ZnO), manganese oxide (Mn3O4), and iron oxide (Fe3O4), have intrinsic toxicity potential. Particularly with iron oxide due to its frequent usage in nanomedicine. Nanoparticles made from these metal oxides in general can induce cytotoxic effects, meaning they cause harm to cells. However, these adverse effects are often very useful in cancer cell therapies, so it is not completely destructive. Another chemical component investigated in the context of nanoparticle toxicity is silver (Ag), as it can be widely used and is easily found in the environment. The cytotoxic effects of silver nanoparticles include induction of stress, DNA damage, and apoptosis, which is essentially the elimination of unwanted cells.9 The PM10 Literature, which is the largest database on nanoparticle toxicity that originated from inhalation, highlights the particle terminology in relation to ambient effects. The data is provided in the following table, labelled Table 1: (Table 1)10 PM10 particles are particles with diameters with 10 micrometers or less, having proven to be a powerful drive for research with nanoparticles. Due to their potential toxicity and small size, when breathed they penetrate the lungs. High concentrations of exposure to this could lead to effects such as coughing, wheezing, asthma attacks, bronchitis, high blood pressure, heart attacks, strokes and even premature death.11 The table gives insight into the difference in toxicity of engineered nanoparticles. Most of the PM10 mass is considered to be non-toxic and so the idea that there are components within PM10 which drives the pro inflammatory effects have risen, making other particles like CDNP (Combustion Derived Nanoparticles) to be a much more likely candidate, more on that in Section 2.3. The higher numbers of nanoparticles used, in addition to their small size, suggests that they each have a larger surface area per unit mass, or a larger surface area to volume ratio. Particle toxicology suggests that for toxic particles generally, increased particle surface equals to increased toxicity. Substantial toxicological data and limited data from epidemiological sources also support the contention that nanoparticles in PM10 are important drivers of such adverse effects as well. These adverse effects include, but are not limited to, respiratory diseases such as cardiovascular disease, or inflammations in the interior such as pulmonary inflammation. This could result in changes in membrane permeability, which may in turn impact the potential for particles to distribute beyond the lung. Such instances include the impairing of vascular function after the inhalation of diesel exhaust pipes. The downside of these data collected is that it is still limited and not all studies of nanoparticles have shown significant translocation from the lung to the blood. In the past decade, the most striking effects of nanoparticles have been observed and recorded, and is displayed in Table 2, along with the particle type which has been tested with: (Table 2)12 The key difference between the dangers in nanoparticles and “traditional” particles is that due to its reduced volume and size, they simply would be more potent to cause similar effects. Several of these effects are just quantitatively different from fine particles. The other large problem is that the introduction of nanoparticles also gave rise to new types of effects not seen previously in larger particles. For instance, mitochondrial damage in ambient nanoparticles, infections through olfactory epithelium in manganese dioxide, gold, and carbon substances, platelet aggregation from single walled carbon nanotubes (SWCNT) and latex carboxylic acids, and cardiovascular effects from PM particles and SWCNTs.13 Other reported risks of nanoparticles are summarised in Table 3: (Table 3)14 Drawing attention back to iron oxide (Fe3O4) nanoparticles, these nanoparticle compounds have been used in drug delivery and diagnostic fields for a duration of time now. These nanoparticles bioaccumulate in the liver and other organs in different organ systems. In vivo studies have shown that after entering the cells, iron oxide nanoparticles remain in cell organelles such as endosomes and lysosomes, release into cytoplasm after decomposing, and contribute to cellular iron poll. Magnetic iron oxide nanoparticles have been observed to accumulate in the liver, spleen, lungs, and brain after inhalation, showing its ability to cross the blood brain barrier. Research shows that the toxic effects are exerted in the form of cell lysis, inflammation, and blood coagulation.15 The exposure of cells to a high dose of iron oxide nanoparticles leads to the formation of excess reactive oxygen species (ROS), which is essentially a type of unstable molecule which contains oxygen in its cell and can easily react with other molecules in the cell. This can affect the normal cell with corresponding apoptosis or cell death. Similar metals like iron, zinc, magnesium, etc. also negatively impact certain genes associated with age related proteins and longevity, and hence, could potentially be detrimental.16 Reduced cell viability (healthiness) has been reported as one of the most common toxic effects of iron oxide nanoparticles in in vitro studies. Iron oxide nanoparticles coated with different substances have shown varying cell viability results. For instance, the toxicity of the tween-coated supermagnetic iron oxide nanoparticles, which has 30 nm in diameter, on murine macrophage cells, has been reported that low concentration of these iron oxide nanoparticles (ranging between 25 -200 µg/mL for 2 hours of exposure) shows an increase in cell toxicity in comparison to high concentrations (ranging between 300 – 500 µg/mL for 6 hours of exposure). Dextran-coated iron oxide nanoparticles, which are a biocompatible material extensively used in biomedical applications to coat nanoparticles to prevent agglomeration and toxicity, still yielded results of varying degrees in cell toxicity after 7 days of incubation despite this added protection.17 Overall, this highlights how the cytotoxicity in metal components in nanoparticles makes their application in medicinal use to be dangerous for the patient. 2.3 - Impacts of nanotechnology on the environment Unfortunately, the implementation of nanotechnology in medicine, although aims to target organisms, would have adverse side effects that aren’t limited to the organism itself. The process of manufacturing these nanomaterials, results in these nanoparticles entering the environment through intentional releases as well as unintentional releases such as atmospheric emissions and solid or liquid waste streams from production facilities. Furthermore, nanoparticles used in other products such as paint, fabric, or personal and healthcare products also enter the environment proportional to their usage. Especially in today’s economy, the purchasing of these cosmetic items and beauty products are at an all-time high. More of that in Section 2.4. Emitted nanoparticles would ultimately be deposited on land and water surfaces. Nanoparticles on land have the potential to contaminate soil and migrate into surface and ground waters. These particles in solid wastes, wastewater effluents, or even accidental spillages can be transported to other aquatic systems by wind or rainwater runoff, severely damaging ecosystems and other natural habitats, simultaneously destroying the homes of other living organisms and possibly the organisms themselves as well. However, the biggest release in the environment tends to come from spillages associated with the transportation of manufactured nanomaterials from production facilities and other manufacturing sites, with the aim of intentional releases for environmental applications. Once again, exposure through inhalation occurring is a leading factor of nanoparticle dangers. Airborne particles composed of nanomaterials with miniscule sizes may agglomerate into larger particles or longer fibre chains, changing their properties and potentially impacting their behaviour in the indoor and outdoor environments as well. This would in turn affect the way they’d affect the human body after exposure and entry.18 CDNPs are also an important component that drives the adverse effects of environmental particulate air pollution. Combustion-derived nanoparticles originate from several sources such as diesel soot, welding fume, carbon black and coal fly ash. Besides affecting people by inducing oxidative stress and exerting genotoxic effects, their components are an environmental and occupational hazard. Diesel exhaust particles are the most common CDNP in urban environmental air and in environmental pollution. Pulverised coal combustion is a common and efficient method of coal burning in power stations. The pulverised coal is blown into the furnace and burned off producing a fly ash emission. While this particulate emission is usually controlled and moderated, these control methods are not 100% effective, and some particles are still released into the environment.19 On of the largest problems with this is that there is a large gap in the literature of research between nanotoxicology in humans and in the environment. Out of the 117 included studies, by BMC Public Health, only 5 had assessed the environmental impact of exposure to nanoparticles. The significant gap in the scientific literature has been highlighted by multiple authors. With the growing production and usage of nanoparticles, undoubtedly this has gradually led to a diversification of emission resources into both the aquatic and soil environment. As the release of nanoparticles into the environment primarily enter during its production, during application, and disposal of products containing nanoparticles as stated previously, these emissions occur both indirectly and directly to the environment. Nevertheless, the most prominent way in which nanoparticles are released is during the application phase and afterwards, the disposal phase. Studies have shown that only about 2% of the production volume is emitted. Further of use of biomarkers such as soil samples and soybean seeds have been used as natural checks and to determine the toxicity of the environment.20 The following study, released in papers by Medline, ScienceDirect, Sage Journals Online, Campbell Collaboration, Cochrane Collaboration, Embase, Scopus, Web of Science, CINAHL, Google, and Google Scholar, includes reviews from 23 countries across several continents, the majority originating from Europe and Central Asia. Reportedly the United States had the highest number of publications, followed by China, India, and Saudi Arabia. Yet most of the studies focused on assessed impact on human health, while only 5 studies focused on assessed effects on the environment, and a shocking 3 studies on both human health and environmental impact. This can be depicted in Figure 2: (Figure 2)21 The studies investigated the environmental and human health effects from inorganic-based nanoparticles, as well as carbon-based nanoparticles. What is more concerning is the fact that attention was diverged unequally, focusing more on the human health aspect in comparison to their impacts on the surrounding environment as well. As a result, despite knowing that most nanoparticles are toxic to some extent on their surfaces, less research has been conducted to determine effectively how to reduce this toxicity to make them more compatible to the environment and negatively impact it less. 2.4 - The shaping of the economy and the wider world Science is a social endeavour. Inevitably, it will be tangled up with socioeconomic issues. Whilst science logistically would be operating outside the controversial hand of politics, in the end, innovation in the scientific field affects these economic considerations and inequalities. Technology itself is neutral; its capacity and potent can be operated by anyone. Yet none of these technological advancements are impartial because in every usage of this, there will always be a motive and a need for profit.22 Unfortunately, the method of producing and manufacturing advanced technologies such as nanoparticles is not a simple, nor cheap process. Naturally, that would mean that using it for targeted drug delivery and other utilisations would be an expensive method of medical treatment. For instance, the business of nanomedicine had an estimated value of $53 billion USD in 2009. By 2025, the industry is projected to reach a total market value of around $334 billion USD. The increasing number of new generation nanotherapeutics will soon enter the market, upping the market value overall. According to the Grand View Research Report, the United States remains the leader in the nanomedicine industry, owning 46% of the total international nanomedicine revenue in 2016, followed by Europe, including major industries in the market such as Pfizer.23 With western countries being primarily the driving force in the advancement of technological development, the distribution of such equipment would be heavily tilted to one side. Less fortunate countries would unlikely be seeing the implementation of nanotechnology in medicine as opposed to other high-income countries. Personalised medicine, for things such as rare diseases, further creates obstacles for drug development, which once again, is more prominent in the countries lacking sufficient healthcare. As a result, large biotech companies find these places and medicine less financially rewarding to invest in compared with universal drugs. Furthermore, nanotechnology connotes the use of the most advanced technological tools for medical ends, for which reason discussions over its socioeconomic effects are of heavy significance, even though they are thoroughly missing from today's discourse. This gives rise to ethical issues, highlighting how geopolitics come into play with the handling of medicine. Especially with countries in power and the wealth disparities, this emphasises the detrimental gap between the rich and the poor and thus the accessibility of nanomedicine around the world as well.24 3.0 - Methodology Fortunately, the technological advancements we benefit from today has allowed scientists and researchers to have developed better nanotechnology and refined flaws. These include, but are not limited to, using different metal compounds and compositions in nanoparticles to reduce toxicity, even more precise nanoparticles for precision in disease diagnosis and prevention, making them more biocompatible, and DNA specialised nanoparticles. One such example is theranostic nanoparticles. Theranostic particles are essentially multifunctional nanomaterial systems, well designed and specialised in specific and personalised disease management by combining diagnostic and therapeutic capabilities into one biocompatible and biodegradable nanoparticle. The engineering of theranostic particles can be done through multiple ways. For instance, loading therapeutic drugs like anti-cancer drugs into existing imaging nanoparticles such as quantum dots or iron oxide nanoparticles, or engineering unique nanoparticles such as porphysome technology with intrinsic imaging and therapeutic properties, alongside modifications with polyethylene glycol and different targeting ligands to improve blood circulation half-life and tumour active targeting capability. This helps solve the problems with nanoparticles accumulating in tumour tissue based on its enhanced permeability and retention effect. Tumour actively targeted theranostic nanoparticles are being developed by further conjugating different targeting ligands to recognise and selectively bind to receptors overexpressing on certain tumour cell surfaces, such as tumour vasculature targeting, which has been considered a good, applicable approach for most functioned organic and inorganic nanomaterials. The targeting ligands could include antibodies, small peptides or molecules, engineered proteins, etc. In addition, theranostic nanoparticles have been developed to target other receptors, such as prostate-specific membrane antigens (PSMA) in prostate cancer and the urokinase plasminogen activator receptor (uPAR) in pancreatic cancer. Theranostic nanoplexes, which contain multi-treating therapy imaging reporters like radioisotopes, and a PSMA-targeting component, was developed to deliver small interfering RNA (siRNA) and a prodrug enzyme to PSMA-expressing tumours. This nanoplex was investigated using the non-invasive multi-treating therapy imaging to evaluate its diagnostic aspects of PSMA imaging, as well as its conversion of prodrug to cytotoxic drug. Results showed that there was no significant immune response or obvious toxicity to the liver or kidney that had been observed. However, the downside to theranostic nanoparticles is that ideally, they must be able to quickly and selectively accumulate in targets of interest, be able to report biochemical and morphological characteristics of diseases, efficiently deliver the sufficient number of drugs on demand without damaging healthy organs and be cleared from the body within hours or biodegraded into nontoxic byproducts. Even though numerous types of both organic and inorganic theranostic nanoparticles have been developed in the last decade for treating diseases such as cancer, none of them has satisfied all the specified criteria yet.25 CRISPR/Cas systems are also a prime example of how nanotechnology has been effectively implemented in medicine. CRISPR is a revolutionised technology with the ability to cleave target nucleic acids with high precision and programmability. However, issues such as insufficient cellular entry, degradation in biological media, and off-target effects makes CRISPR unreliable at times. By incorporating nanotechnology into this, it enables and improves intracellular and targeted delivery, stability, stimulus-responsive activation in target tissues, and adjustable pharmacological properties. Nanotechnology can also enhance CRISPR-mediated detection by increasing sensitivity, facilitating simpler readouts during implementations, as well as reducing time to readout.26 The Cas-9 enzyme is a large ribonucleoprotein (RNP), which helps with transcription, translation and regulating gene expression and regulating the metabolism of RNA. The incorporation of nanotechnology with Cas systems provides a powerful new means for the fast, specific, and ultrasensitive detection of protein biomarkers, whole cells, and small molecules, in addition to nucleic acid targets. Using nanomaterials as signal readouts can enhance detection sensitivity or reduce the need for special equipment for signal detection.27 Nanorobots are a relatively new technology that contain small monitors that allow them to navigate to specific parts of the body. They have had primary applications so far as drug delivery agents. One example of this is the “origami nanorobot” developed by researchers at Arizona State University, consisting of a flat sheet of synthetic DNA that is coated in a blood-clotting enzyme and can be folded into various shapes. It is injected into the bloodstream and programmed to seek out tumour cells. When located, it attaches to their surface and injects them with a blood-clotting enzyme, starving the tumour cells of the blood it needs to survive on. Further research carried by ASU showed promising therapeutic potential from the way it overall prevented the spread of metastasis in cancer. “Smart pills” are also utilised as nanoscale sensors that are designed to detect the presence of diseases long before the symptoms may become apparent to the present. Invented by Jerome Schentag, a professor of pharmaceutic science at the University of Buffalo, it aimed to electronically track and instruct the delivery of a drug to a predetermined location in the gastrointestinal tract. In addition, the built in miniature camera helps monitor the bowels or colon to detect internal bleeding. Data collected by the pill is transmitted wirelessly to a device controlled by a patient, allowing for continuous monitoring of internal health conveniently.28 Finally, Green Nanotechnology-Driven Drug Delivery Assemblies aim to help reduce the toxicity of the nanoparticles used, to benefit both the target organisms and the surrounding environment. By employing the concept of green chemistry and green engineering into the manufacturing of nanobiomedicine, the aim is to create eco-friendly nanoassemblies with less environmental and health related negative impacts. As a result, the combination of green nanomaterials with drugs, vaccines, or diagnostic markers will hopefully be the next step to propel the field of green nanomedicine. Many inorganic nanoparticles have been introduced to the market and manufactured on the principles of green engineering and nanotechnology. For example, gold and silver nanoparticles are less toxic compared to other metals like copper and zinc. Quantum dots, organic polymeric nanoparticles, mesoporous silica nanoparticles, dendrimers, and nanostructuredi lipid carriers have also been used. These nanomaterials are attached with drugs, DNA molecules, or specific enzymes, proteins or peptides for further handling in nanomedicine purposes. Research now continues to establish the differences and effectiveness in the yield of nanomedicine produced using normal bioengineering compared to manufacturing through elaborative green bioengineering principles. This will allow scientists to opt for the best manufacturing conditions for nanoparticles in the future. Especially with DNA molecules, using DNA based drug delivery devices in nanotechnology aims to increase personalised targeted drug therapies to further improve diagnosis and target drug delivery.29 Conclusion In summary, the innovations in technology over the years have undoubtedly brought into light newer and improved methods to diagnose and treat patients in the medical field. The progress made with nanotechnology is proof of its immense potential and its history of successes highlights its usefulness and capabilities. Most vitally, its ability to act as a drug carrier for specific drug delivery is what makes the usage of nanotechnology so special and powerful, especially in cases when dealing with diseases and illnesses which are difficult to cure, such as cancer. By being able to provide detailed visualisations of organism interiors, to assist in genetic modification and editing genetic information, the versatility of nanoparticles is something that shouldn’t be overlooked either. As discussed above, however, the drawbacks of the implementation of nanoparticles in medicine must not be overlooked either. Nanotoxicology has been proven time and time again for its setbacks, and the way it can affect both organisms and the surrounding environment brings into question whether the usage of nanoparticles is really the best strategy in the medicinal field currently. Not to mention the extreme costs for this utilisation, which, amongst many other things, contribute to the increasing economic gap between income classes. Nevertheless, history has shown how the relentless efforts of scientists and researchers have overcome obstacles in the medicinal field, and undoubtedly, these drawbacks provided by nanotechnology would be resolved in future years, as I strongly believe the potential of using nanotechnology for targeted drug delivery is too much to pass up on, and I think many others would feel the may. References [1] PubMed Central. (2019). The History of Nanoscience and Nanotechnology: From Chemical–Physical Applications to Nanomedicine. [Online]. National Center for Biotechnology Information. Last Updated: 27 December 2019. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982820/#:~:text=The%20American%20physicist%20and%20Nob [Accessed 18 February 2024]. [2] PubMed Central. (2018). 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Author: Steffi Kim In today’s highly interconnected world, collaboration and group work are becoming more prevalent than ever. But from brainstorming ideas to dividing up tasks, group work introduces a whole new dimension of challenges. Why do some groups fail, while others succeed? How do panels of experts sometimes reach such poor decisions? This article will briefly explore four common psychological phenomena, and provide solutions to boost group productivity and success in all spheres of life. Groupthink Groupthink is when a group exhibits bad decision-making due to intense pressure to conform and suppress dissenting opinions. Early on, the group becomes bent on a particular course of action, usually dictated by a leader, and ignores any facts or evidence suggesting a different approach. The group becomes insulated and closed off from outside opinions, creating echo chambers and a facade of unanimity. Groupthink can become dangerous when ethical considerations or broader consequences are ignored, and the group fails to acknowledge risks or create a contingency plan. When electing his 2008 Security Defense Team, the President of the United States, Barack Obama, specifically mentioned how he wanted to avoid groupthink. Groupthink stems from the well-intentioned desire to maintain harmony and agreement, and is more prevalent in groups with a strong “us against the world” mindset. To avoid groupthink, encouraging debate and avoiding rushed conclusions are key. Designating a “devil’s advocate” to raise concerns, or having the low-ranking members speak first so they don’t have to contradict the leader, are also ways to combat this phenomenon. The Abilene Paradox The Abilene Paradox occurs when a group collectively comes to a decision that none of the individual members actually agree with. The problem is not agreement—all the members agree on a point, yet the group itself moves in the opposite direction. For instance, a company leader proposes a new initiative because she thinks that that’s what everyone else wants to hear. The employees all secretly harbour doubts but speak highly of it to others because they believe that everyone else supports it. The result? A failed initiative that no one actually wanted, and a waste of time and resources. The Abilene Paradox is surprisingly common and can be due to action anxiety, where people imagine what great disasters could occur if they speak their mind, and use this as an excuse for inaction. Although similar to groupthink, the Abilene Paradox is fundamentally different. In groupthink, individuals self-censor and change their own beliefs to align with the group, whereas, in the Abilene Paradox, individuals are aware that they personally disagree. To avoid this trap, group members must consider the real risk of inaction and remaining silent. Group Polarisation Group Polarisation refers to the likelihood of a group taking more extreme stances than the initial opinions of its members. When surrounded by like-minded individuals, people are more likely to deepen their own commitment to a cause, in part due to a desire to be socially accepted. As group discussion goes on, hearing confirming arguments made by other group members reinforces and strengthens an individual’s own beliefs. Over time, as groups self-segregate and discuss amongst themselves, the differences between groups become more and more exaggerated, known as the Accentuation Effect. Liberal groups become more liberal, intellectual groups become more intellectual, and conservative groups become more conservative. Group polarisation has crucial political and societal implications, and groups with diverse opinions and healthy disagreement are less susceptible. Social Loafing In every group, there are usually a few people who don’t pull their own weight. Social Loafing is the psychological term used to describe individuals who put in less effort in group settings than they would on their own. Studies have shown that when asked to shout and clap as loud as they could, when told they were in a group, the noise each individual produced was three times less than the loudest sound when they were alone. The same pattern holds for tug-of-war, where the collective effort of teams was half the sum of the individual efforts. When individual effort is not measured, responsibility is dispersed amongst the group, with no individual held accountable. Monitoring individual progress and making individual actions distinguishable reduces social loafing. Social loafing also decreases if the group has a challenging goal, and incentives to work hard. Individuals heighten their own efforts when they view other team members as incompetent, and forming smaller groups where members feel indispensable is an effective way to reduce freeriding. References: “Groupthink.” Psychology Today. Accessed June 15, 2024. https://www.psychologytoday.com/us/basics/groupthink. Harvey, Jerry B. “The Abilene Paradox: The Management of Agreement.” Organizational Dynamics 17, no. 1 (June 1988): 17–43. https://doi.org/10.1016/0090-2616(88)90028-9. Hoffman, Riley. “Social Loafing in Psychology: Definition, Examples & Theory.” Simply Psychology, September 7, 2023. https://www.simplypsychology.org/social-loafing.html. Myers, David G. Social Psychology, 2012. https://diasmumpuni.files.wordpress.com/2018/02/david_g-_myers_social_psychology_10th_editionbookfi.pdf.

Author: Lekh Parekh Abstract We conducted a survey to study the psychological impact of the COVID-19 pandemic and the associated lockdown on the mental health of a section of young people in urban India. We present the findings from data collected from more than 200 young people within the 14 to18 year age group. We explored early signs of anxiety and depression. Hypothesis: The duration of the 2020 Covid pandemic and the subsequent lockdown has a direct association with negative psychological states in young people, specifically early symptoms of anxiety and depression. Introduction: On the 24th March, 2020, the Indian Prime Minister Narendra Modi announced India’s first nationwide three week lockdown due to the Covid -19 pandemic. Stretching from 25th March to 14th April 2020, the lockdown sparked a buzz of problems, criticism and hope. While multiple studies have focused on the welfare of deprived communities and on the physical and psychological impact on adults, our study specifically focuses on one group, i.e. 14 to 18 year old in a cosmopolitan city. A lack of attention towards this age group and the psychological well-being of this population could have a catastrophic impact on motivation, social interaction and general health for years to come. Methodology: The survey respondents were 14 to 18 year old individuals who were characterized by a higher socioeconomic status with access to computers and social media, attending private schools. This group is more likely to aspire to enroll in foreign Universities. They were all residents of Mumbai, a cosmopolitan city in India. The primary data was collected as part of a survey via a Google Form, with most questions designed to be answered on a linear scale of 1 to 5 (1 indicating “Not at all” and 5 indicating “Very”) to indicate severity of psychological symptoms. The form included a consent section to document consent from both participant and parent/guardian. Participants ticking the consent box were considered as having opted in to the survey. The respondents’ names and identifying details were not part of the Google Form in order to ensure anonymity of the respondents.  The form was disseminated among different school social media groups.  A total of 226 completed forms were returned. This collection of the data was during the active phase of lockdown. Results and Analysis: Anxiety: ​The following symptoms were considered: 1) Worry about the Future 2) Duration of Sleep3) Difficulty in concentration Worry about the Future: University applications are a significant consideration for high school students within this specific socio-economic group. Figure: 1 As seen in Figure 1, nearly 63.3 % of respondents were very worried (scores of 4 or 5) about their future college applications. High degree of worry about this aspect at a young age within the short period of three weeks of lockdown can be construed as an early sign of anxiety. Duration of Sleep: Figure: 2 Duration of sleep is an indicator of a rested body and a peaceful mind. We considered a duration of sleep of 4 hours a night or less as an inadequate duration of sleep. Almost 13% of the survey respondents reported an inadequate duration of sleep. Inadequate sleep is a sign of several psychological disturbances, including anxiety and depression. Difficulty in Concentration: Figure: 3 As seen in Fig 3, more than half of the respondents (56.2%) found it hard to concentrate for long periods of time. Depression: We considered the following as early symptoms of depression. 1)      Helplessness 2)      Irritability 3)      Loss of Energy Helplessness Figure: 4 As seen in Figure 4, more than 55.8% of the respondents reported a sense of helplessness at scores of 4 and 5. This feeling of helplessness indicates the possibility of a depressed psychological state. Irritability: Figure: 5 Almost 72% of survey responders were feeling more irritated than before the pandemic which is a potential marker for the mood changes of depression. Loss of Energy: Figure: 6 As seen in Figure 6, more than 48% of survey responders scored 4 or 5 when asked to rate the extent of loss of energy. This is nearly half of the entire group. A prolonged period of inactivity due to loss of energy can have multiple effects ranging from deterioration of physical health to reduction of future career and life chances. Therefore, detecting this symptom in its early stages is vital in preventing long term impacts. Despite these effects, we also found that a large proportion of the young people were partaking in positive coping activities involving exercise/yoga (56.6%), socialising with friends (72.6%) and games and interactions with their family (45.6%). These could potentially be protective. Strengths and Weaknesses: Weaknesses: Many of the group of 226 young people were likely to have known other respondents to the survey which could be a source of bias. Unfortunately, the economically challenged section could not be studied. The study population consisted of English speaking pupils of private schools from relatively affluent families. None of them were school dropouts or working to earn a wage. This limits the generalisability of the results. The impact of the pandemic on economically deprived groups from the same age category is likely to be very different and much more severe but this conclusion cannot be drawn from our study. Strengths: Considering the fact that this study is psychological, most of the questions in the survey were designed to be on a Likert scale which provided information about the severity of the symptom in question. As the survey form was anonymised and avoided direct interview in person or on the phone, it minimised bias, for example, from societal bias that could have led to the need to present a positive view to an interviewer. As the survey form was likely to have been completed by the respondents on their own alone as part of their natural social media interaction, it is less likely to have introduced familial involvement and sources of bias. As the survey could be completed by the respondents online at a convenient time and in their own space, it is likely to have provided triggers for introspection and reflection. Potential for future research: A group with similar characteristics could be surveyed again to see differences in psychological state after the end of lockdown. Conclusion: A high proportion of young people surveyed in this study experienced symptoms of anxiety and depression during the brief period of three weeks of lockdown. An association was found between the period of lockdown and some symptoms of depression and anxiety. Our society has advanced to such an extent that young people are no longer content to spend time at home in isolation devoid of activity and social contact. The digital world has created the expectation for sensory or mental stimulation constantly. Restriction of normal social mobility and a sense of uncertainty about the future, exacerbated by the disruption of normal routines due to school closures as well as the inescapable 24/7 news coverage were unusual and hitherto unexpected and unprecedented challenges. This set of circumstances could be difficult to adapt to as an adult and even more challenging for a young person to process. It is in this context that the recent lockdown posed a risk to the overall wellbeing of the surveyed group. However, as the duration of this concerning psychological state is likely to have been short at the point of the survey, it is plausible to consider that a significant proportion of respondents would not progress into clinical anxiety and depression, especially if addressed in the early stage. Further, recovery and resumption to a semblance of normality after the end of nationwide lockdown are likely to have reversed the adverse psychological findings reported in this study. However, given that a vaccination programme for COVID-19 will take a couple of years to be implemented and pockets of resurgence and localised lockdowns in the future remain a possibility, our survey highlights the need for awareness and recognition of remedial measures. The measures described above could be efficacious in reducing the detrimental impact of lockdown on the mental health of young people. Bibliography: “Anxiety Disorders.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 4 May 2018, www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/syc-20350961. Schimelpfening, Nancy. “8 Ways to Improve Your Mood When Living With Depression.” Verywell Mind, 20 Mar. 2020, www.verywellmind.com/tips-for-living-with-depression-1066834. Melinda. “Coping with Depression.” HelpGuide.org, www.helpguide.org/articles/depression/coping-with-depression.htm. Holland, Kimberly. “20 Ways to Fight Depression.” Healthline, Healthline Media, 16 Oct. 2001, www.healthline.com/health/depression/how-to-fight-depression#today-vs.-tomorrow.

Author: Maia Zaman Arpita Challenging assumptions and paving innovative routes, Ann Kiessling's courageous quest for knowledge has revolutionised our comprehension of reproductive biology and stem cell research. Ann Drue Anderson, who later became Ann Kiessling, was born in 1942 and raised in Oregon. She grew up as a science enthusiast; she pursued a nursing degree from Georgetown University and the University of Virginia. Further intensifying her journey towards her aim, she earned degrees in chemistry and organic chemistry from Central Washington University and a Ph.D. in biochemistry from Oregon State University. She showcases her immense interest in research to award the world with both groundbreaking and controversial research. One of her first and notable achievements includes the discovery of reverse transcriptase in normal human cells (1979) as a part of her post-doctoral degree. Her discoveries illuminated the link between viruses and cancer, challenging traditional beliefs and opening the door for more investigation into the influence of retrovirus sequences in human genes and their effects on human development and physiology. Currently, Kiessling is acknowledged as a trailblazer in both reproductive biology and stem cell research. Her researches have awarded us with valuable insights into the key areas within the discipline. Motivated by a desire to pursue research; that is overlooked by larger organisations due to political considerations, she established the Bedford Stem Cell Research Foundation in 1996. The main objective of this independent, non-profit institute was the application of stem cells to cure incurable diseases like HIV and spinal cord injuries. Throughout Kiessling’s career, she has occupied roles in various esteemed establishments, such as Oregon Health Sciences University and Harvard Medical School.Her immaculate research and innovative approaches has earned her numerous honours and awards for her pioneering research and creative approach to science, including the Alumni Achievement Award from the University Of Virginia School Of Nursing. The influence of her work persists, inspiring and educating scientists and researchers globally. Her impact on virology, reproductive biology, and stem cell research will endure, shaping our comprehension of human health and disease for years to come.