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Background: Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP)-glucagon-like peptide 1 (GLP-1) receptor agonist being evaluated for the treatment of various metabolic disorders. We performed a meta-analysis of randomized data on the effects of tirzepatide on serum lipid levels. Methods: We systematically searched the PubMed and ClinicalTrials.gov databases for relevant data from randomized controlled clinical trials. All articles were screened, reviewed, and extracted by at least two independent authors, with conflicts resolved by consensus. Four hundred and thirty-three records were identified in the initial literature search; 18 of them were identified for full-text review, and 14 of those were systematically reviewed and included in the analysis. The meta-analysis was performed using an inverse variance random-effects model. Results: Fourteen articles that reported data from 13 randomized controlled clinical trials were included in the review. Nine trials had a low risk of bias, two had a moderate risk, and two had a high risk of bias. The pooled analysis showed that tirzepatide was efficacious at improving all lipid markers, including cholesterol and triglycerides. Moreover, a clear dose response trend was visible across results from groups taking 5, 10, and 15 mg of tirzepatide. Conclusion: There is growing evidence to support the use of tirzepatide in patients with metabolic diseases such as type 2 diabetes mellitus, metabolic syndrome, and obesity. Our results demonstrate that tirzepatide significantly improves all aspects of patient metabolism and might be superior in this regard to conventional agents such as insulin formulations or traditional GLP-1 agonists. [ABSTRACT FROM AUTHOR]

Background Traditional assessments often lack flexibility, personalized feedback, real-world applicability, and the ability to measure skills beyond rote memorization. These may not adequately accommodate diverse learning styles and preferences, nor do they always foster critical thinking or creativity. The inclusion of Artificial Intelligence (AI), especially Generative Pre-trained Transformers, in medical education marks a significant shift, offering both exciting opportunities and notable challenges for authentic assessment practices. Various fields, including anatomy, physiology, pharmacy, dentistry, and pathology, are anticipated to employ the metaverse for authentic assessments increasingly. This innovative approach will likely enable students to engage in immersive, project-based learning experiences, facilitating interdisciplinary collaboration and providing a platform for real-world application of knowledge and skills. Methods This commentary paper explores how AI, authentic assessment, and Student-as-Partners (SaP) methodologies can work together to reshape assessment practices in medical education. Results The paper provides practical insights into effectively utilizing AI tools to create authentic assessments, offering educators actionable guidance to enhance their teaching practices. It also addresses the challenges and ethical considerations inherent in implementing AI-driven assessments, emphasizing the need for responsible and inclusive practices within medical education. Advocating for a collaborative approach between AI and SaP methodologies, the commentary proposes a robust plan to ensure ethical use while upholding academic integrity. Conclusion Through navigating emerging assessment paradigms and promoting genuine evaluation of medical knowledge and proficiency, this collaborative effort aims to elevate the quality of medical education and better prepare learners for the complexities of clinical practice. [ABSTRACT FROM AUTHOR]

Background: Traditional medical education often lacks contextual experience, hindering students' ability to effectively apply theoretical knowledge in real-world scenarios. The integration of the metaverse into medical education holds great enormous promise for addressing educational disparities, particularly in lower-middle-income countries (LMICs) accompanied by rapid technological advancements. This commentary paper aimed to address the potential of the metaverse in enhancing basic sciences education within the constraints faced by universities in LMICs. We also addressed learning design challenges by proposing fundamental design elements and a suggested conceptual framework for developing metaverse-based teaching methods. The goal is to assist educators and medical practitioners in comprehensivley understanding key factors in immersive teaching and learning. Discussion: By immersing medical students in virtual scenarios mimicking real medical settings and patient interactions, the metaverse enables practice in clinical decision-making, interpersonal skills, and exposure to complex medical situations in a controlled environment. These simulations can be customized to reflect local healthcare challenges, preparing medical students to tackle specific community needs. Various disciplines, including anatomy, physiology, pharmacy, dentistry, and pathology, have begun leveraging the metaverse to offer immersive learning experiences, foster interdisciplinary collaborations, and facilitate authentic assessments. However, financial constraints pose a significant barrier to widespread adoption, particularly in resource-limited settings like LMICs. Addressing these challenges is crucial to realizing the full potential of metaverse technology in medical education. Conclusion: The metaverse offers a promising solution for enhancing medical education by providing immersive, context-rich learning experiences. This paper proposes a conceptual framework and fundamental design elements to aid faculty educators and medical practitioners in effectively incorporating metaverse technology into their teaching methods, thus improving educational outcomes in LMICs. [ABSTRACT FROM AUTHOR]

The World Wide Web and the advancement of computer technology in the 1960s and 1990s respectively set the ground for a substantial and simultaneous change in many facets of our life, including medicine, health care, and medical education. The traditional didactic approach has shifted towards more dynamic and interactive methods, leveraging technologies such as simulation tools, virtual reality, and online platforms. At the forefront is the remarkable evolution that has revolutionized how medical knowledge is accessed, disseminated, and integrated into pedagogical practices. The COVID-19 pandemic also led to rapid and large-scale adoption of e-learning and digital resources in medical education because of widespread lockdowns, social distancing measures, and the closure of medical schools and healthcare training programs. This review paper examines the evolution of medical education from the Flexnerian era to the modern digital age, closely examining the influence of the evolving WWW and its shift from Education 1.0 to Education 4.0. This evolution has been further accentuated by the transition from the static landscapes of Web 2D to the immersive realms of Web 3D, especially considering the growing notion of the metaverse. The application of the metaverse is an interconnected, virtual shared space that includes virtual reality (VR), augmented reality (AR), and mixed reality (MR) to create a fertile ground for simulation-based training, collaborative learning, and experiential skill acquisition for competency development. This review includes the multifaceted applications of the metaverse in medical education, outlining both its benefits and challenges. Through insightful case studies and examples, it highlights the innovative potential of the metaverse as a platform for immersive learning experiences. Moreover, the review addresses the role of emerging technologies in shaping the post-pandemic future of medical education, ultimately culminating in a series of recommendations tailored for medical institutions aiming to successfully capitalize on revolutionary changes. [ABSTRACT FROM AUTHOR]

Background: More than 75 genetic susceptibility loci have been implicated with hyperglycemia. SNPs in genes linked with satiety, insulin sensitivity, BMR (Adiponectin, FTO, and MC4R), and inflammation and autoimmunity (TNF-a) have been shown to have a relationship with metabolic syndrome. Objectives: To measure the frequency of ADIPOQ, FTO, MCR4, and TNF SNPs in metabolic syndrome patients and controls, and to assess the association of these with hyperglycemia and adiposity status. Methods: A cross-sectional study was conducted. Baseline investigations including lipid profiles, blood glucose levels, and BMI calculation were conducted for n=113 Metabolic Syndrome and n=47 healthy controls. Tetra ARMS PCR and gel electrophoresis were conducted for Adiponectin rs266729, Adiponectin rs1501299, FTO rs9939609, MCR4 rs1297013, and TNF rs1800629. Statistical analysis was performed using SPSS version 26. Results: Difference was observed in lipid profiles (including LDL, triglycerides, and cholesterol but not HDL), body fat percentage (p= 0.034), and both fasting (p=0.000) and random (p=0.000) blood glucose levels among metabolic syndrome patients versus controls. Adiponectin rs1501299, FTO rs9939609, and MCR4 rs1297013 showed genotype frequency differences between groups. Spearman's correlation was applied to test any association of risk allele with study variables and MCR4 rs1297013 showed an independent association with Fasting Blood Glucose Level (r=0.238; p=0.024) irrespective of age, weight, or gender. Conclusion: MCR4 rs1297013 polymorphism is an independent risk factor leading to hyperglycemia in the study population, however, no other SNPs were identified to carry a significant risk. Large-scale genome-wide studies are required to identify the unique set of risk genes for the Pakistani population. [ABSTRACT FROM AUTHOR]

The intrauterine environment and early-life nutrition are regulated by maternal biomarkers in the blood and breast milk. We aimed to explore epigenetic modifications that may contribute to differential chemerin expression in maternal plasma, colostrum, and breast milk and find its association with fetal cord blood and infant weight at 6 weeks postpartum. Thirty-three gestational diabetes mellitus (GDM) mothers and 33 normoglycemic mothers (NGT) were recruited. Two maternal blood samples (28th week of gestation and 6 weeks postpartum), cord blood, colostrum, and mature milk were collected. Methylation-specific polymerase chain reaction and enzyme-linked immunosorbent assay were conducted. The weight of the babies was measured at birth and 6 weeks postpartum. Serum chemerin levels at the 28th gestational week and 6 weeks postpartum were significantly lower for the NGT group as compared to the GDM group; (P < 0.05). Higher colostrum chemerin concentrations were observed in the GDM group and remained elevated in mature milk as compared to NGT (P < 0.05). Colostrum and breast milk chemerin levels showed an independent association with infant weight at 6 weeks postpartum (r = 0.270; P = 0.034) (r = 0.464; P < 0.001). Forty percent GDM mothers expressed unmethylated chemerin reflecting increased chemerin concentration in the maternal blood. This pattern was also observed in newborn cord blood where 52% of samples showed unmethylated chemerin in contrast to none in babies born to normoglycemic mothers. The results of this study highlight the critical importance of altered chemerin regulation in gestational diabetic mothers and its effect during early life period and suggest a possible role in contributing to childhood obesity. [ABSTRACT FROM AUTHOR]

Introduction: Asthma has been classified as a major non-communicable disease by the WHO. With the worsening air quality index worldwide, the burden of asthma has increased specifically in children. The focus of the management strategy of asthma has shifted from traditional pharmacological treatments towards non-pharmacological preventive and control therapy in recent decades. The use of high-efficiency particulate air (HEPA) filters is one of the methods to achieve that, despite extensive research, the efficacy of HEPA filters in this context of effectiveness and usage guidelines remains unclear. Our study aims to examine the effect of HEPA filters in (1) reducing clinical visits or hospital admissions or the number of exacerbation events, (2) reducing asthma symptoms, (3) increasing asthma symptom-free days, (4) reducing indoor particulate matter 2.5 levels for children with asthma aged 5-17 years and (5) improving quality of life., Methods: We will conduct a systematic review using MEDLINE, Google Scholar and Scopus as databases, article selection is planned to be restricted to randomised controlled trials only (2002-2025). We are following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines developed specifically for the protocol(s). Two reviewers will screen the studies independently and assess study quality using the Cochrane Risk of Bias Tool for Randomised Trials, V.2. The results of outcome measure(s) will be summarised in tables. If the studies are sufficient, we will also perform a quantitative analysis by creating forest plots and subgroup analysis will be performed if required. Lastly, publication bias will be assessed using a funnel plot and Egger's test and reported accordingly., Ethics and Dissemination: We will conduct a systematic review, therefore there is no need for a formal ethical review. After successful completion, our results will be published in a peer-reviewed journal., Prospero Registration Number: CR42024494949., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Women with gestational diabetes mellitus (GDM) and their offspring have an increased risk of adverse perinatal and long-term health outcomes, which may be attributable to epigenetic modification of diabetes and obesity susceptibility genes. We aimed to investigate the methylation patterns of eight genes in GDM and normoglycemic (NG) mothers, and their respective offspring. Methods: This cross-sectional study, conducted at Aga Khan University from August 2019 to December 2022, recruited pregnant women in the first trimester of gestation from the outpatient obstetrics clinic. Participants were classified as NG or GDM based on the Society of Obstetricians and Gynecologists Pakistan. Venous blood samples were collected from mothers and cord blood from neonates. Peripheral blood mononuclear cells were used for DNA extraction and methylation analysis using methylation-specific PCR. Maternal and neonatal clinical data were recorded. Statistical analysis was performed using R, including binary logistic regression to assess the association between various gene methylation levels and GDM. Results: The study found that GDM mothers had significantly higher fasting blood glucose, 2-hr OGTT, and serum carboxymethyl lysine (CML) levels compared to NG mothers, but no significant differences in neonatal birth weight or serum CML levels. Chemerin methylation was significantly lower in GDM mothers and their babies, while NAMPT, MTNR1B, FNDC5, FAT4 , and FTO methylation levels were higher in GDM offspring compared to NG offspring. GDM mothers also had higher methylation levels of brain-derived neurotrophic factor gene ( BDNF ). Multivariable binary logistic regression identified methylation levels of maternal BDNF and neonatal MTNR1B to be independently associated with GDM. Conclusions: Our study shows a trend of epigenetic modifications in both GDM mothers and their offspring in various genes related to metabolism and inflammation, suggesting an intergenerational transmission of increased risk of developing metabolic disorders. These findings emphasize the need for high throughput studies, early screening, tight glucose control during pregnancy, and postnatal follow-up to mitigate long-term health risks.

There is a radical shift in teaching and learning pedagogies to engage the learners in healthcare profession. It was a tough challenge for Pakistani educators of an esteemed university to motivate and assess the learners for concept absorption and critical reasoning using creative approaches. Teaching and learning styles have changed fundamentally from conventional teacher centred to inquiry-based student-centred approach. Classroom teaching in recognised nursing and medical institutes in Pakistan have transformed to blended and entirely online methodologies with the integration of diverse active learning strategies. The educators grapple to engage the millennials and to encounter this, gaming technological platform was used to facilitate the learners for maximum integration, active participation, and create an exciting learning experience. Various e-gaming tools, such as Kahoot, Jamboard, Padlet Wall, Ed-Puzzle, Mentimeter, etc., were used in nursing and medical courses and were highly appreciated by the leaners to retain, review, and self-assess.

Objective: To assess the association of oxytocin receptor (rs53576) and melatonin hormone receptor 1B (rs1387153) gene single nucleotide polymorphisms with psychological symptoms in women with gestational diabetes mellitus., Methods: The case-control study was conducted from May 1 to June 1, 2022, at the Department of Physiology, University of Karachi, in collaboration with the Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, and the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi. Fifty gestational diabetic pregnant women and ninety healthy pregnant women were recruited. Sanger sequencing was performed to assess the genotypic frequency and polymorphic variation of all subjects. Perceived stress scale and diabetes-related distress scale were used to assess the stress levels. Data was analysed using SPSS 23., Results: Of the 140 subjects, 90 (64.3%) were controls with mean age 24.96±4.35 years, and 50 (35.7%) were cases with mean age 28.78±5.25 (p<0.05). Mean body weight and mean gestational age were not significantly different between the groups (p>0.05). Melatonin hormone receptor 1B rs1387153 frequency was significantly different between the groups (p<0.05). Among the cases, a significant mean difference for regimen distress scores between AA and GG was observed for oxytocin receptor rs53576 (p=0.04). A significant mean difference in sum of PSS, diabetes-related stress, total diabetes- related stress and emotional distress was noted between CC and TT genotypes for melatonin hormone receptor 1B rs1387153 (p=0.001)., Conclusion: MTNR1B rs1387153 genotypes were associated with perceived stress, diabetes-related stress, diabetic distress, and emotional burden, while OXTR rs53576 genotypes were associated with regimen distress in GDM women.

Objective: To explore knowledge, attitudes and practices of laypersons and health professionals towards foetal programming, and factors affecting it., Methods: The mixed methods study was conducted at the Aga Khan University, Karachi, from January 20, 2021 to May 13, 2022, and comprised adults of either gender with access to social media platforms. Data was collected using an online survey questionnaire in English and Urdu developed to capture responses from a diverse pool of participants. The survey tool was circulated through WhatsApp, Facebook and Instagram. Two focus group discussions were conducted; one with laypersons in group A and the other with health and allied professionals in group B. Data was analysed using SPSS 21, while data related to focus group discussions was subjected to thematic analysis., Results: Of the 358 participants, 173(48.3%) were in group A and 185(51.7%) were in group B. There were 34(18.4) subjects in group A and 27(15.6) in group B who had knowledge of foetal programming (p>0.05). Only factors related to father's health and dietary elements on the foetus were significantly different between the groups (p<0.05). Thematic analysis led to the formation of 3 overarching themes: parent's lifestyle, comorbidity and diet on foetal health; myths and cultural beliefs regarding foetal development; and the need for training / awareness for practitioners and community., Conclusions: Lack of knowledge and misinformation about foetal programming and development was common among health professionals and laypersons.

Objective: To assess the availability and use of automated external defibrillators in various public and private establishments, and to assess knowledge, attitude and practices related to its use., Methods: The telephone-based survey was conducted from March to August 2019 in Karachi after approval from the ethics review committee of the Aga Khan University, Karachi, and comprised public and private establishments identified through purposive sampling based on the standard requirements for automated external defibrillators installation. Data was collected using a predesigned questionnaire which was pilot-tested for reliability and validity. Data was analysed using SPSS 23., Results: Of the 53 establishments, 32(60.4%) were private and 21(39.6%) were public. Overall, 9(17%) establishments were aware of automated external defibrillators and 1(1.9%) had an automated external defibrillator on the premises. Also, 25(47.2%) establishments believed that having an automated external defibrillator on the premises would be useful, while 25(47.2%) were undecided. Besides, 22(41.5%) establishments said they would consider installing an automated external defibrillator on the premises, while 24(45.3%) were undecided. Finally, 37(69.8%) establishments expressed a positive desire to get trained in giving basic life support., Conclusion: There was a need for a city-wide automated external defibrillator placement project for a reduction in mortality due to out-of-hospital cardiac arrest.