Vitamin D and Lipid Profiles in Infertile PCOS and Non-PCOS Females.

OBJECTIVE: This research is aimed to explore the relationship between vitamin D and lipid profile in females with PCOS and non-PCOS infertile female subjects. STUDY DESIGN: Comparative descriptive study. Place and Duration of the Study: Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi, Pakistan and Jinnah Postgraduate Medical Centre, Karachi, Pakistan in collaboration with the Australian Concept Infertility Medical Centre, from February 2021 to March 2023. METHODOLOGY: A total of 180 infertile women with 120 PCOS and 60 non-PCOS were enrolled. The lipid profile and BMI of the patients were acquired from desk records, and vitamin D was estimated by enzyme-linked immunosorbent assay (ELISA). Participants were classified according to their vitamin D levels as sufficient (30-100 ng/ml), insufficient (20-29 ng/ml), or deficient (below 20 ng/ml). Median, interquartile range, frequency, and percentages were described. Statistical significance was calculated by Mann-Whitney U and Chi-square tests with p-values of 0.05. RESULTS: Females with PCOS had significantly low vitamin D (p <0.001). Total cholesterol, low-density lipoprotein, very low-density lipoprotein, and triglyceride levels were significantly increased, and high-density lipoprotein cholesterol (HDL) was less in comparison to the non-PCOS group (p <0.001). A significant increase in total cholesterol, triglycerides, low-density lipoproteins, and very low-density lipoproteins was found in the vitamin D deficient subgroup compared with insufficient or sufficient groups (p = 0.05). CONCLUSION: The study provides a link between females with PCOS and abnormalities in lipid profile. Decreased vitamin D levels in females with PCOS were linked with an abnormal lipid profile characterised by rise in cholesterol, triglycerides, and low-density lipoproteins which may lead to metabolic abnormalities. KEY WORDS: Vitamin D, Polycystic ovary syndrome, Metabolic syndrome, Body mass index, Lipid profile.

Acceptance of team-based learning by students and faculty: A pilot study.

Background & Objective: Team-Based Learning (TBL) is an interactive instructional approach characterized by collaborative peer teaching in both large and small group settings. The study aims to assess usefulness of the TBL in enhancing student learning outcomes and engagement in graduate classes. Methods: This mixed method study was conducted from January 2023 till July 2023 at the Department of Biological & Biomedical Sciences at Aga Khan University, Karachi, Pakistan, a questionnaire was distributed to graduate students in Endocrine and Reproductive course after TBL on 'Hormonal changes in Pregnancy'. Focus group discussion (FGD) was held with facilitator of this TBL and the students; results of both arms were then triangulated. Results: All (four) students responded affirmatively regarding guided self-preparation, quality of application exercises, satisfaction in terms of student's engagement, a positive attitude and self-accountability. Themes identified by FGD of both students and facilitators were 'Students Engagement in Peer Learning, 'Conducive Learning Environment', "Time is Capital in TBL' and 'Conceptual learning.' Conclusion: The pilot study confirmed the utility of TBL by students as well as the facilitators. Students came with prior preparation, got engaged in problem-solving activities and received feedback from peers and the expert facilitators. The conducive environment enhanced their engagement, enabled them to actively apply the content and benefit from guided supervision.

Association of catechol-o-methyltransferase gene polymorphism with preeclampsia and biomarkers of oxidative stress: Study protocol for a prospective case-control study in Pakistan.

BACKGROUND: Preeclampsia is one of the three leading causes of worldwide maternal mortality. Oxidative stress-mediated endothelial damage is expected to be an ultimate common mechanism in the pathophysiology of preeclampsia. The role of bioamines is also well-established in the induction of preeclampsia. This project is aimed to understand the factors which may affect the induction, progression, and aggravation of preeclampsia and oxidative stress during pregnancy. This study will explore the methylation pattern of the Catechol-O-methyltransferase gene to determine its role in the pathogenesis of preeclampsia, association of Val158Met polymorphism with a wide range of oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in preeclamptic Pakistani women. METHODS AND ANALYSIS: In this prospective case-control study, 85 preeclamptic and 85 normotensive pregnant women will be recruited in their third trimesters. DNA will be extracted from peripheral blood and Val158Met polymorphism in the Catechol-O-methyltransferase gene will be examined on PCR amplified product digested with Hin1II (NlaIII) restriction enzyme, further validated by Sanger sequencing. Methylation-sensitive PCR will also be performed. Oxidative stress biomarkers, antioxidant vitamins, bioamines, and catechol-O-methyltransferase levels will be measured by ELISA. The data will be used to correlate maternal and fetal outcomes in both groups. DISCUSSION: This study will help to identify and understand the multifactorial path and cause-effect relationship of gene polymorphism, oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in the pathogenesis and aggravation of preeclampsia in the Pakistani population. The outcome of this project will be particularly helpful in reducing the incidence of preeclampsia and further improving its management.

Identification of a Single Nucleotide Polymorphism of Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP) Gene and Its Dysregulated Pathway Through VDR-VDBP Interaction Network Analysis in Vitamin D-Deficient Infertile Females.

INTRODUCTION: The prevalence of female infertility in Pakistan is currently estimated at 22%, and emerging research suggests that vitamin D (VD) deficiency (VDD) may play a significant role in influencing female fertility. The focus of this study was to investigate the single nucleotide polymorphism (SNP) patterns within the VD binding protein (VDBP). The study aimed to explore dysregulated pathways and gene enrichment through an interaction network analysis, specifically focusing on the interplay between the VD receptor (VDR) and VDBP in females experiencing unexplained infertility (UI) coupled with VDD. METHODS: A cross-sectional study was conducted on VD-deficient, fertile, and UI female subjects. VDBP and VDR were assessed by enzyme-linked immunoassay and genotyping performed. FunRich (version 3.1.3; http://funrich.org/index.html) was employed for analysis of the identified proteins: VDR and VDBP and with their mapped gene datasets, gene enrichment, and protein-protein interaction (PPI) network. RESULTS: The mean VD and VDR values of infertile females were significantly lower than those of fertile females. VDBP in infertile females (median (IQR)): 296.05 (232.58-420.23)) was lower than that of fertile females (469.9 (269.57-875.55), (p=0.01)). On sequence analysis, a mutation rs 4588 SNP (Thr 436 Lys) was found in exon 11 of the VDBP gene of UI females, but no mutation in exons 8 and 9 of the VDR gene, with some insignificant intronic variants, was observed. The proteins such as plasma membrane estrogen receptor signaling pathway (p < 0.001), VDR, SMAD3, NCOR1, CREBBP, NCOA1, STAT1, GRB2, PPP2CA, TP53, and NCOA2 were enriched after biological pathway grouping when VDR was made the focused gene and directly interacting with VDBP. CONCLUSION: The females with UI exhibited significantly low VD, VDBP, and VDR. The plasma membrane estrogen receptor signaling pathway was enriched in VDD infertile females.

The ongoing evolution of mentorship: Advancing the formal mentorship program at AKU-SONAM.

Objective: To investigate the perceptions of mentors, mentees, administrators (including chairs, co-chairs, and coordinators of the mentoring program), and leadership regarding the Faculty Mentorship Program at AKU School of Nursing and Midwifery (AKU-SONAM). Additionally, the study aimed to explore the strengths and challenges faced by the program. Methods: A qualitative exploratory study on mentorship was carried out in AKU-SONAM from February till December 2021. In this study we conducted purposive criterion sampling. The study participants included mentors, mentees, administrators, and the dean of AKU-SONAM. An interview guide was developed, validated, and reviewed by experts. After piloting, two focused group discussions and three in-depth interviews were conducted. Results: Thematic analysis of the data revealed the following themes: "Nurturing growth and development in mentoring relationships," "Establishing a strong foundation for effective mentoring," and "Opportunities for growth and development through overcoming challenges." Conclusion: The participants expressed confidence in the existing support system, leadership, and mentorship program at the institution. They highlighted the significance of regular monitoring to recognize areas of improvement uphold high standards and ensure excellence.

Correlation of serum kisspeptin and leptin with non-obstructive azoospermia: A cross-sectional study in a subset of Karachi population.

Objective: To determine the association of serum kisspeptin, leptin, and other hormonal profile with non-obstructive azoospermia (NOA) in infertile male subjects. Methods: This cross-sectional study was conducted at Australian Concept Infertility Medical Center, and Ziauddin University, Karachi from March 2018 to March 2020. The duration of the study was two years. Serum samples of 106 azoospermic participants were taken. Division of the subjects was done on a histological basis into obstructive azoospermia (OA) n=36, NOA n=70 which were further divided into spermatid maturation arrest (SMA), n=41, and sertoli cell-only syndrome (SCOS) n=29. Serum kisspeptin and leptin were measured by ELISA (Cloud-Clone Corp). Results: The follicle-stimulating hormone (FSH) (p<0.01), luteinizing hormone (LH) (p<0.01), thyroid-stimulating hormone (TSH) (p<0.01), and estradiol (p<0.01) was significantly high in the NOA group. However, kisspeptin was significantly decreased (p<0.01) in the NOA group. In the multivariate analysis after adjusting for other variables, the results showed that with the decrease in kisspeptin, the chances of being NOA were increased. Moreover, with the increase in Leptin, FSH, LH, and TSH the chances of being NOA were significantly enhanced. Conclusion: Serum kisspeptin, leptin, FSH, LH, TSH, and estradiol can be a potential marker for NOA in terms of better diagnosis, targeted therapeutic management, and the decision to proceed with surgical intervention.

Genetic association of vitamin D receptor gene with female infertility.

BACKGROUND: Infertility is defined as failure to achieve a clinical pregnancy after 12 months of unprotected intercourse. It affects 15% of couples globally and 22% of couples within Pakistan. Female infertility can be caused by numerous genetic or environmental factors including hormone imbalances and exposure to chemicals or radiation. The prevalence of vitamin D deficiency among the adult population was reported to be 14-59% with a higher prevalence in Asian countries. Furthermore, the expression of Vitamin D receptor (VDR) can play a vital role in the reproductive organs of females. Hence, the aim of our present study was to check the association of VDR polymorphisms with infertile females. For this purpose, blood samples were collected for genotyping of four known VDR mutations [FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232), and BsmI (rs1544410)] via PCR-based RFLP assay. RESULTS: Genotyping indicated that FokI, TaqI, and ApaI are associated with infertility (p = 0.004*, p = 0.013*, and p = 0.033*, respectively). However, BsmI did not show any significance. Multinomial regression analysis indicated that FokI heterozygous genotypes increase the risk of infertility by 2.5 times (hetero: OR = 2.5, 95%, p = 0.001*) as compared to wild type. Heterozygous genotypes of TaqI and ApaI were found to play a protective role and reduce the risk of infertility by 58 and 52%, respectively [TaqI: OR = 0.42, 95%, p = 0.004*, ApaI: OR = 0.48, 95%, p = 0.01*, respectively] as compared to wild type. Multinomial logistic regression analysis was also performed for allelic data as well. CONCLUSION: Thus, it could be summarized that among the studied polymorphisms of VDR, FokI SNP greatly increased the risk of infertility, while TaqI and ApaI genotypes protect from infertility. However, BsmI does not influence the risk of infertility in Pakistani females.

Unraveling the Genetic Associations of DENND1A (rs9696009) and ERBB4 (rs2178575) with Infertile Polycystic Ovary Syndrome Females in Pakistan.

Polycystic Ovary Syndrome (PCOS) is a complex genetic disorder in reproductive-aged women which is associated with comorbidities of reproductive, metabolic, cardiovascular, endocrine, and psychological nature. PCOS is the most common cause of anovulatory infertility. Pathogenesis of PCOS involves strong interaction between environmental and genetic factors. Many Single-Nucleotide Polymorphisms (SNPs) have been associated with PCOS in different populations. Currently, very limited association studies of PCOS and infertility have been done on Pakistani population. The variants DENND1A rs9696009 and ERBB4 rs2178575 are significantly associated with PCOS in Chinese and European populations. These candidate genes regulate the production of androgen hormone, Anti-Mullerian Hormone (AMH), and luteinizing hormone. All these hormones are involved pathogenesis of PCOS and infertility. The aim of the study is to find an association of DENND1A rs9696009 and ERBB4 rs2178575 variants with PCOS in infertile Pakistani females. In this case-control study, 300 infertile females were recruited. The cases (n = 160) were infertile female diagnosed with PCOS (Rotterdam Criteria), and controls (n = 140) were infertile women with no evidence of PCOS. The genomic DNA was isolated, and genotyping was done by PCR-Restriction fragment length polymorphism and further validated by DNA Sanger Sequencing. The Chi-Square analysis showed rs2178575 (ERBB4) was significantly associated with infertility (χ2 = 10.282, p = 0.005852) while rs9696009 (DENND1A) did not show any significant association (χ2 = 3.10, p = 0.212036). Furthermore, multinomial logistic regression analysis was performed and revealed that rs2178575 (ERBB4) heterozygous genotypes (GA) and mutant genotypes (AA) decrease the risk of infertility by 0.541 times (OR = 0.541, 95% CI = 0.314-0.930, p = 0.026) and 0.416 times (OR = 0.416, 95% CI = 0.228-0.757, p = 0.004), respectively, compared to wild-type genotype (GG). The ERBB4 variant is significantly associated with PCOS infertile women and genetically indicated that ERBB4 (rs2178575) decreases the risk of infertility in females having PCOS.

Seeds of trust ripe as luscious fruits: Faculty mentorship forum at Aga Khan University Medical College.

Background & Objective: Faculty members require mentoring in all stages of their professional development. Aga Khan University (AKU) has initiated mentorship programs for students and faculty at AKU Medical College (AKU- MC) and AKU School of Nursing and Midwifery (AKU-SONAM). This study aimed to explore perceptions of mentors, mentees, administrators (chairs, co-chairs, founder members and coordinators of the mentoring program) and leadership and further investigate the strengths and challenges faced by 'Faculty Mentorship Program' at AKU- MC. Methods: We conducted a qualitative exploratory study from February till December 2021 after approval from AKU using purposive criterion sampling. Mentors, mentees, administrators and dean of AKU- MC were included in the study. The interview guide was developed, validated and reviewed by experts. After piloting, four focused group discussions and 8 in-depth interviews were conducted in AKU- MC. Results: The findings described the transition from informal to formal mentorship, identified challenges faced by mentors and mentees and suggested the role of leadership / administrators. The themes identified were "Continuous improvement of mentoring practices", "Building strong foundations for mentoring relationships", and "Growth and development through challenging experiences". Conclusion: The faculty mentorship program at AKU-MC was in line with the goals and vision of the institution. All participants identified the need of additional resources, administrative support, rewards, incentives and recognition of mentors for sustainability of the program.

An interplay of Progesterone, Leukemia Inhibitor Factor and Interleukin-6 in the window of implantation; Impact on fertility.

BACKGROUND: The process of implantation is crucial for the initiation of conception and hence fertility. In addition to a number of factors, it is regulated by a cross talk of gonadotrophins [Luteinizing Hormone (LH), Follicle Stimulatory Hormone (FSH)], ovarian steroids [Estrogen (Et), Progesterone (Pt)] and cytokines [Leukemia inhibitory factor (LIF) and Interleukin 6 (IL6)]. These biomarkers are chief players of implantation. OBJECTIVE: We aimed to explore the role of gonadotrophins (LH, FSH, LH/FSH ratio), ovarian steroids (Et, Pt) and cytokines (LIF, IL6) in the implantation process. This aim was achieved by comparing these hormones and cytokines in the fertile and infertile groups [Polycystic ovaries (PCOs), endometriosis, unexplained infertility (Uex-IF)] and finding their association in all study groups. METHODS: A case control study conducted from October 2020-March 2023. A total of 135 infertile women (with PCOs, Uex-IF, and endometriosis) and 177 fertile women (matched for age and BMI) were selected. Levels of 'Et', 'Pt', 'LIF' and, 'IL6' were estimated using Enzyme Linked Immunosorbent Assay (ELISA). LH and FSH values were obtained from hospital desk records. The Independent Student'st-test was used to compare fertile and infertile groups. One-way ANOVA test was used to compare more than two groups, and Pearson's chi-square (χ2) test was employed to compare percentages of variables. Pearson correlation analysis was performed to assess the associations and correlations. A p value < 0.05 was considered statistically significant. RESULTS: Significantly higher levels of LIF and IL6 were observed in fertile women compared to infertile women. Pt levels were significantly greater in the fertile group than in the infertile group. The FSH/LH ratio was significantly higher in the fertile group. Among infertile women, PCOs (71%) and Uex-IF (91%) exhibited lower Pt levels than the fertile controls (p < 0.01), but these levels remained within the reference range (RR). Among the fertile group (81%), levels of LIF within the RR were significantly higher compared to those with Uex-IF (49%) and females with endometriosis (37%). Moreover, the highest number of participants (57%) with Uex-IF exhibited IL6 levels significantly below the RR in comparison to the fertile group and infertile groups (PCOS and endometriosis). However, lower levels of IL6 were observed in women with Uex-IF. In the control group, LIF exhibited a significant positive correlation with IL6 (r = 0.370), Pt (r = 0.496), Et (r = 0.403), and LH (r = 0.428). Among women with PCOs, LIF showed a significant positive correlation with IL6 (r = 0.443), Pt (r = 0.607), and LH (r = 0.472). In cases of Uex-IF, LIF demonstrated a significant positive correlation with IL6 (r = 0.727). Females with endometriosis displayed a significant positive correlation between LIF and IL6 (r = 0.535) as well as Pt (r = 0.605). In fertile women, a positive correlation was observed between LH and IL6 (r = 0.197, p = 0.009), LIF (r = 0.428, p = 0.000), Pt (r = 0.238, p = 0.001), and Et (r = 0.356, p = 0.000). Furthermore, a positive correlation was found between LH and LIF (r = 0.472, p = 0.000) in women with PCOs. CONCLUSION: Elevated levels of Pt were found to increase the production of LIF in fertile females. However, infertile females with PCOs and Uex-IF exhibited deficient levels of Pt, supporting its role as a biomarker for successful implantation in infertile women. These females showed decreased levels of gonadotropins as well as reduced LH/FSH ratio and diminished secretion of receptivity marker LIF, in addition to reduced Pt secretion. This suggests that reduced gonadotropin levels contribute to a lower LH/FSH ratio, resulting in decreased Pt secretion and ultimately leading to low levels of LIF, thereby causing impaired implantation in women with PCOs and Uex-IF. The exploration of low levels of LIF in patients with endometriosis requires further investigation. The significantly low levels of IL6 in the Uex-IF group elucidate the role of this cytokine in association with decreased Pt and LIF synthesis within this group.

SIRT1 and antioxidants in infertile females: Exploration of the role of vitamin D.

BACKGROUND: Deficiency of silent information regulator 1 (SIRT1) can trigger inflammation, mitochondrial malfunctioning, and apoptosis through the hypothalamic-pituitary-ovarian axis, producing poor quality oocytes, leading to infertility. Normal vitamin D (VD) levels promote SIRT1 activity required for optimal fertility, and low levels of either may result in fertility problems owing to cell-membrane de-stabilization, increased autophagy, DNA damage leading to increased reactive oxygen species and mitochondrial dysfunction. Therefore, in this study, we want to estimate the levels of VD, SIRT1 and antioxidants (MnSOD; manganese superoxide dismutase, GR; glutathione reductase, visfatin) and oxidants (adrenaline & cortisol) in individuals living with infertility and explore the association of VD with SIRT1 expression (levels), antioxidants, and oxidants contributing to infertility in women. The significance of this study is that it highlights the importance of maintaining optimal levels of VD for reproductive health in females. METHODS: This cross-sectional study included 342 (135 infertile and 207 fertile) female subjects. Serum levels of MnSOD, SIRT1, visfatin, GR, VD, adrenaline, and cortisol were analyzed by ELISA and were compared in fertile and infertile samples using the Mann Whitney U test. RESULTS: There were significantly high levels of VD, SIRT1, GR, MnSOD and visfatin in fertile female participants. However, mean adrenaline and cortisol levels were higher in infertile samples with a significant negative correlation with VD. A significant negative correlation of VD with MnSOD, SIRT1, visfatin and GR was observed (p <0.01). In VD subset groups, MnSOD levels were significantly high in VD sufficient groups however, adrenaline and cortisol levels were significantly high in groups suffering from VD deficiency. CONCLUSIONS: Deficiency of VD is associated with a decrease in SIRT1 and other antioxidants, which may deter natural reproductive functions leading to infertility. Further studies are required to determine the cause-effect relationship of VD deficiency on conception and interpretation of the involved mechanism.

Basics of faculty-to-faculty mentoring: A process to identify support and challenges.

Faculty mentoring is relatively new in health sciences literature. Faculty mentors are considered to have multiple roles including being a supervisor, teacher, or a coach. Little or no attention to formal mentoring of faculty allows faculty to seek informal mentoring, creating a risk of unexpected outcome. There is dearth of literature with respect to formal mentoring programs from the subcontinent. Although, informal faculty mentoring has been in place but there is no standard faculty mentorship model to be followed at Aga Khan University Medical College (AKU-MC). An observational study was conducted in September 2021 at AKU MC with convenient sampling to share the perceptions of the AKU-MC faculty mentors in a faculty mentorship workshop so that further advanced level faculty development workshops could be planned in this area. Twenty-two faculty mentors participated to share their perspectives on the responsibilities of faculty mentor, faculty mentee and the institution to see faculty grow and to have a sustainable mentorship programme. Challenges faced by the faculty mentors during the process of mentorship were also discussed. Majority of the participants emphasized on the role of the faculty mentor to be supportive, guiding, reflective and formative (respond to the emotional needs, encourage, effective communication, know own limitations, observe, provide feedback). Faculty mentor role modeling, ability to maintain confidentiality, creating and maintaining mentor-mentee relationship, availability of framework of formal mentoring in an academic institution and opportunities within the academic setting to learn mentorship were the main challenges of being a faculty mentor. The process provided valuable training and education to the faculty for the development and strengthening of formal mentoring program. Faculty recommended that institutions should provide the opportunity for development of junior faculty mentors by organizing capacity building activities.

Interplay of "leukemia inhibitory factor receptor gene" (rs3099124) polymorphism, leukemia inhibitory factor and ovarian steroids with unexplained infertility.

OBJECTIVE OF THE STUDY: To explore the association of leukemia inhibitory factor receptor (LIFR) gene variant rs3099124, ovarian steroids, and leukemia inhibitory factor with unexplained infertility in Pakistani females. METHODOLOGY: A case-control investigation in which eighty-one (81) females with unexplained infertility and one hundred and sixty-two (162) fertile counterparts (age and body mass index compared) were recruited between October 2016 and 2018. Ten milliliters of venous blood was collected from all participants. "Genomic DNA" was taken out from lymphocytes in peripheral blood samples. "Tetra Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR)" was constructed through software "Primer-I". Amplification was carried out by "T-ARMS-PCR" followed by subsequent sequencing for confirmation and extensive consonance. Estradiol, Progesterone and Leukemia Inhibitory Factor (LIF) were measured in serum by ELISA. RESULTS: Statistically significant difference was noticed in genotype frequency in "LIFR-gene variant; rs3099124" (χ2 = 28.222, P value < 0.01) between research participants. Although, rs "3099124" "AA" (OR = 0.000; 95%CI = 0-0) and "GA" genotypes (OR = 0.525; 95%CI = 0.226-1.22) showed non-significant safety/protection against unexplained infertility yet minor/risk allele "A" frequency was greater in women with unexplained infertility suggesting a possible explanation of implantation failure. LIF concentration varied between fertile and infertile groups (χ2 = 9.857, P < 0.05) revealing significant threat of unexplained infertility in women with decreased LIF concentration (OR = 2.316, 95%CI = 1.214-4.416). Progesterone was significantly related to unexplained infertility in both study groups (χ2 = 20.347, P < 0.05). High progesterone reduced the possibility of unexplained infertility (OR = 0.306; 95% CI = 0.166-0.567). CONCLUSION: LIFR gene variation (rs3099124) and reduced LIF secretion may cause implantation failure in women with unexplained infertility.

MTHFR-c 677C>T polymorphism and male infertility: An analysis in a cohort of Pakistani men / Polimorfismo MTHFR-c 677C>T e infertilidad masculina: un análisis en una cohorte de hombres pakistaníes

Objective: To analyze existence of an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with male infertility. Materials and methods: A case–control study was conducted from June 2017 to August 2018 in which 88 infertile and 40 fertile were recruited. Polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) assay was carried out to study the allelic frequency of C677T polymorphism. The differences in allelic and genotypic frequencies of C677T locus between fertile and infertile groups were evaluated by the Pearson chisquare test. A logistic regression model was used to calculate Odds ratios and 95% confidence intervals, p value<0.05 was considered significant. The Hardy–Weinberg equilibrium was tested using HWE software. Results: In infertile subjects, frequency distribution of CC allele was (60.2%), the CT allele was (30.7%) the TT allele was (9.1%) and in the fertile controls the frequency was CC allele (75%), CT allele (20%) and TT allele (5%) respectively. Analysis revealed MTHFR 677 CC genotype associated significantly with male infertility (p<.046, OR=2.385; 95% CI=1.014–5.608); Frequency of CT (30.7%) and TT (9.1) genotypes were higher in infertile men as compared to CT (20%) TT (5%) in fertile controls but statistically these were not significantly different (p=0.097; OR=0.455; CI=0.179–1.153 and p=0.431; OR=0.526; CI=0.107–2.599 respectively). Significant association of age and BMI with MTHFR genotypes and infertility was observed. Conclusion: Our results showed that MTHFR C677T polymorphism is not a risk factor for male infertility in our Pakistani population. (AU)

Objetivo: Observar el efecto del polimorfismo C677T en metilenetetrahidrofolato reductasa (MTHFR) en la infertilidad masculina. Materiales y métodos: Se realizó un estudio de casos y controles desde junio de 2017 hasta agosto de 2018 en el que se reclutaron 88 infértiles y 40 fértiles. Se llevó a cabo el ensayo reacción en cadena de la polimerasa (PCR) - polimorfismo de longitud de fragmento de restricción (RFLP) para estudiar la frecuencia alélica del polimorfismo C677T. La prueba de chi-cuadrado de Pearson se utilizó para estimar las diferencias en las frecuencias alélicas y genotípicas del locus C677T entre fértiles e infértiles. Los cocientes de probabilidad se obtuvieron mediante el análisis de regresión logística con intervalos de confianza del 95%, siendo significativo un valor de p<0,05. Se aplicó el equilibrio Hardy-Weinberg (HWE). Resultados: En sujetos infértiles, la distribución de frecuencia del alelo CC fue del 60,2%, la del alelo CT, del 30,7%, la del alelo TT, del 9,1%, y en los controles fértiles la frecuencia fue alelo CC fue del 75%, la del alelo CT, del 20%, y la del alelo TT, del 5%, respectivamente. El análisis reveló el genotipo CC MTHFR 677 asociado significativamente con infertilidad en los hombres (p<0,046, OR=2,385; IC95%: 1,014-5,608). La frecuencia de los genotipos CT (30,7%) y TT (9,1) fue mayor en hombres infértiles en comparación con CT (20%) y TT (5%) en controles fértiles, pero estadísticamente estos no fueron significativamente diferentes (p=0,097, OR=0,455; IC95%: 0,179-1,153, y p=0,431, OR=0,526; IC95%: 0,107-2,599, respectivamente). Se observó asociación significativa de edad e IMC con genotipos MTHFR e infertilidad. Conclusión: Nuestros resultados mostraron que el polimorfismo MTHFR C677T no está asociado con la infertilidad por factor masculino en nuestra población pakistaní. (AU)

Reflection of mentors and mentees at initiation of Faculty Mentorship Program at Aga Khan University: A perspective.

Objectives: To explore perception of mentors and mentees about 'Mentorship Program at Aga Khan University Medical College (AKU-MC) from a structured feedback form. Methods: A retrospective study was conducted for evaluation of mentorship program at AKU-MC during the period from Jan 2019 to March, 2021. Responses on validated "Pre-intervention Probe Forms", from forty-seven mentors and fourteen mentees inducted in the program were reviewed. Confidentiality and anonymity of data were deliberated. All replies to each question were entered in a separate worksheet to determine the frequency and percentage of answers. Responses conveying same message, but worded differently were then grouped. Results: All the mentees (n=14) responded positively to the question on the "understanding of the mentoring program. The mentees (n=12, 86%) recognized the potential of the program to transfer knowledge and skills, (n=11, 79%) supported its role for achievement of goals, (n=7, 50%), acknowledged its role in faculty relationships. The mentors expressed their enthusiasm to help the mentee's in their professional development. They (n=20, 43%) offered support to set career goals, (n=29, 62%) proposed transfer of knowledge, skills, and experiences to achieve goals, (n=15, 32%) decided to be "role models". Some (n=10, 21%) forecasted improved communication skills, (n=14, 30%) boosted leadership capabilities, (n=13, 28%) expected improved work performance, (n=15, 32%) opinioned that networking and leadership qualities will impact the growth of the mentee to meet the university's expectations. Conclusion: Both mentors and mentees recognized the importance of the faculty mentorship program at AKU-MC for professional guidance, development and improvement in work performance.

MTHFR-c 677C>T polymorphism and male infertility: An analysis in a cohort of Pakistani men.

OBJECTIVE: To analyze existence of an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with male infertility. MATERIALS AND METHODS: A case-control study was conducted from June 2017 to August 2018 in which 88 infertile and 40 fertile were recruited. Polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) assay was carried out to study the allelic frequency of C677T polymorphism. The differences in allelic and genotypic frequencies of C677T locus between fertile and infertile groups were evaluated by the Pearson chisquare test. A logistic regression model was used to calculate Odds ratios and 95% confidence intervals, p value<0.05 was considered significant. The Hardy-Weinberg equilibrium was tested using HWE software. RESULTS: In infertile subjects, frequency distribution of CC allele was (60.2%), the CT allele was (30.7%) the TT allele was (9.1%) and in the fertile controls the frequency was CC allele (75%), CT allele (20%) and TT allele (5%) respectively. Analysis revealed MTHFR 677 CC genotype associated significantly with male infertility (p<.046, OR=2.385; 95% CI=1.014-5.608); Frequency of CT (30.7%) and TT (9.1) genotypes were higher in infertile men as compared to CT (20%) TT (5%) in fertile controls but statistically these were not significantly different (p=0.097; OR=0.455; CI=0.179-1.153 and p=0.431; OR=0.526; CI=0.107-2.599 respectively). Significant association of age and BMI with MTHFR genotypes and infertility was observed. CONCLUSION: Our results showed that MTHFR C677T polymorphism is not a risk factor for male infertility in our Pakistani population.

Perception of postgraduate medical residents regarding educational environment at French Medical Institute for Mothers and Children, Kabul Afghanistan.

OBJECTIVE: To assess the perceptions of postgraduate medical education residents regarding educational environment at a medical institution in Afghanistan. METHODS: The descriptive cross-sectional study was conducted from 2017 to 2018 at the French Medical Institute for Mothers and Children, Kabul, Afghanistan, FMIC, and comprised postgraduate medical residents. Dundee Ready Educational Environment Measure was administered to determine the perception of learning environment by the residents' perceptions related to learning, teachers, academic self-perception, atmosphere and social self-perceptions sub scales. Data was analysed using SPSS 22. RESULTS: Of the 63 subjects, 55(87.30%) were males and 42(66.66%) were married. The overall mean age was 30±4.38 years. There was no significant difference in mean subscales scores and overall scores in relation to participants' age, gender, type of specialty, province and year of training (p>0.05). There was a significant difference in students' perception of teachers in relation with the type of specialty (p<0.05). CONCLUSIONS: The educational environment at the medical institution in Afghanistan was perceived by the students of residency programme as conducive.

Neuregulin 4 (NRG4) - the hormone with clinical significance in gestational diabetes mellitus.

This study aimed at determining the association between serum neuregulin 4 (NRG4) and insulin in gestational diabetes mellitus (GDM) and their correlation with other metabolic parameters. A cross-sectional study was conducted from June 2018 to February 2019 at Ziauddin University, Karachi. Pregnant women (n = 80), at 24-28 weeks of gestation, were recruited. Demographic data, anthropometric measurements and antenatal history were recorded. The fasting blood was drawn for testing fasting blood sugar (FBS), NRG4, insulin and lipid profile. The subjects were evaluated for glucose challenge test after 50 g glucose ingestion. NRG4 levels (1.00 ± 0.15) were found significantly high (p < .04) in healthy group compared to GDM (0.95 ± 0.11). In GDM females, high levels for FBS (p < .02) and cholesterol (p < .03) were observed. Homeostatic model assessment of insulin resistance (HOMA-IR) had direct weak association with NRG4, inverse relationship with cholesterol and LDL but significant association (p < .05) with insulin. Significantly high NRG4 in healthy females suggests its potential role in regulating insulin sensitivity. Impact StatementWhat is already known on this subject? Neuregulin 4 (NGR4) is a batokine which plays a potential role in regulating insulin sensitivity, maintaining energy and metabolic homeostasis. Due to its role in lipid and glucose homeostasis, some studies report its role in gestational diabetes mellitus (GDM) but the results were controversial.What do the results of this study add? The study showed that NGR4 levels were significantly low in GDM subjects. Other metabolic factors especially insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were found associated significantly (p < .05) with NGR4.What are the implications of these findings for clinical practice and/or further research? NGR4 can be a potential biomarker for gestational diabetes. Nevertheless, in order to confirm these findings, further studies, with bigger sample size are required to further ascertain the prospects of NRG4 as a potential biomarker for gestational diabetes.