Development and Evaluation of a Peer Mentoring Programme for Postgraduate Medical Residents in Pakistan: A Pilot Study.

OBJECTIVE: To develop, implement, and evaluate the impact of one-year peer mentoring programme for postgraduate medical residents. STUDY DESIGN: Mixed methods. Place and Duration of the Study: The Aga Khan University, Karachi, from January 2019 to December 2020. METHODOLOGY: A survey was administered to junior residents in Medicine, Paediatrics, Pathology, and Radiology residency programmes to identify their academic needs from January 2019 to December 2020. Final-year residents, who served as peer mentors were provided a one-day mentoring workshop, including details of the identified needs. This was followed by one-year intervention in which mentors-mentees met as per mutual feasibility. A structured survey and focus group discussions were conducted to inquire the effectiveness of mentoring. RESULTS: A total of 33 out of 52 (63%) Year 1 residents completed needs analysis survey. Four essential identified areas were research (63%), memory (59%), reading (55%), and time management (53%). Residents reported excelling in areas of research, memory and reading, however, time management needed improvement. Focus group discussions emphasised mentoring as mandatory, including the wide range of skills. CONCLUSION: Senior residents should be trained as mentors of juniors, and semi-structured formal and informal mentoring can be implemented across all residency programmes. KEY WORDS: Mentoring, Residents, Postgraduate, Medical trainees.

Association of Kaiso and partner proteins in oral squamous cell carcinoma.

Objectives: 1. Identification of protein expression and subcellular localization of E-cadherin (E-cad), p120 catenin (P120ctn), and Kaiso in oral cancer (OC). 2. To study the protein expression of cyclin D1 and c-Myc (Kaiso targets) and determine their relationship with the expression and localization of Kaiso. Methods: Histological grading was performed in accordance with Broder's criteria. Expression and localization data for E-cad, p120ctn, Kaiso, cyclin D1, and c-Myc were acquired using immunohistochemistry. Data were analyzed using SPSS version 21. The chi-square test was used to measure the statistical significance of associations, with p < 0.05 as statistically significant. Results: Of 47 OC cases, 36% showed low E-cad expression and 34% showed low p120ctn. Low Kaiso expression was recognized in 78% of tumor specimens. Aberrant cytoplasmic localization of p120ctn was seen in 80.8% cases. Cytoplasmic Kaiso localization was appreciated in 87% of tumor tissues, whereas 29.7% lacked any nuclear Kaiso. Kaiso expression was significantly associated with the expression of cyclin D1 but not with c-Myc. Conclusion: The present study identified a change in the localization of Kaiso in OC. The significance of this in relation to OC and tumor prognosis needs to be investigated with further studies using larger sample sizes and more sensitive molecular tools.

Association between the baseline gene expression profile in periapical granuloma and periapical wound healing after surgical endodontic treatment.

In this study, we have investigated the association between the baseline gene expression profile in periapical granuloma and periapical wound healing after surgical endodontic treatment. Twenty-seven patients aged between 15 and 57 years underwent periapical surgery. The retrieved periapical tissue sample was used for mRNA expression analysis of COL1A1, VTN, ITGA5, IL-4, TNF, ANGPT, VEGFA, and CTGF. All patients were recalled after 6 and 12 months for periapical healing evaluation. Healing was then correlated with baseline gene expression. Healing was observed in 15 patients at the end of 6 months, which increased to 21 patients after 12 months. Six patients showed no healing even after 12 months. Analysis of baseline expression levels of the tested genes with healing status showed the mean relative expression of VTN, VEGFA, ANGPT, TNF, and CTGF to be significantly different (p < 0.05) between the healing group (6 and 12 months) (72.99%) and the non-healing (94.42%) group. Periapical Index scores 3-5 exhibited a positive correlation with ITGA-5 expression. Overexpression of ANGPT and a strong positive correlation between ITGA5 and PAI scores in the non-healing group of patients may suggest these genes to be a potential prognostic biomarker for periapical wound non-healing after surgical endodontic treatment.

Baseline MMP expression in periapical granuloma and its relationship with periapical wound healing after surgical endodontic treatment.

BACKGROUND: Matrix metalloproteinases (MMPs) catalyzes the degradation of the extracellular matrix components and have a major role in many physiological processes including wound healing. In the current study, we examined the correlation of baseline MMPs 1, 2, 7, and 9 expressions with periapical wound healing after surgical endodontic treatment. METHODS: 27 patients aged between 15 and 57 years presenting with chronic apical periodontitis or chronic apical abscess of an anterior tooth with previously attempted or failed root canal treatment were included in this study. During surgical endodontic treatment, tissue from the periapical lesion sample was collected and used for gross histopathological analysis as well as mRNA expression analysis of MMPs 1, 2, 7, and 9. Patients were recalled for follow-up after 6  months to evaluate the healing status both clinically and radiographically and healing was correlated with baseline MMP expression. RESULTS: Out of 27 patients, healing was observed in 15 patients at the end of 6 months, and in 21 patients after 12 months.. Six patients showed no healing even after 12 months. Analysis of baseline MMP 1, 2, 7, and 9 expression levels with healing status showed the mean relative expression of MMP2 and MMP9 to be considerably increased in the non-healing group as compared to the healing group. CONCLUSION: Overexpression of MMP2 and MMP9 may be considered as a potential prognostic biomarker for periapical wound healing after surgical endodontic treatment. However, further studies are desirable to establish its precise relationship with periapical wound healing.

Opuntiol Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells by Upregulating Active Caspase 3 Expression.

BACKGROUND: Glioblastoma Multiforme (GBM) is a deadly tumor with poor prognosis. Resistance to apoptosis considered as an important factor in treatment failure. Therefore, identification of new compounds that facilitates apoptosis is crucial. Natural Anti-inflammatory compounds have emerged as potential anti-cancer agents and should be explored for their apoptotic activity against GBM. Therefore, the present study aims to evaluate growth inhibitory and apoptotic activity of a natural anti-inflammatory compound "Opuntiol" against GBM cell line U87. METHODS: MTT assay was performed to determine the effect of Temozolomide and Opuntiol on growth inhibition of U87 cell. While, TUNEL assay was used to assess their apoptotic activity. To further assess apoptosis, nuclear condensation and nuclear area factor (NAF) was evaluated through DAPI staining. Whereas, active caspase-3 protein expression determined using immunocytochemistry. RESULTS: Significant growth inhibition was observed in U87 cells treated with Temozolomide (IC50 380 µM) and Opuntiol (IC50 357 µM). Temozolomide (p<0.001) and Opuntiol (p<0.001) significantly improved rate of apoptosis when compared to control group. A significant decrease in NAF was also observed in Temozolomide (p < 0.05) and Opuntiol (p < 0.05) treated cells. There was a significant increase in active caspase-3 expression when observed in Temozolomide (p<0.001) and Opuntiol (p<0.05) treated groups as compared to control. CONCLUSION: In conclusion our findings suggests, Opuntiol repress cell viability and possess strong apoptotic activity against GBM cell line U-87. However, further mechanistic studies will be required to confirm whether it can be develop as a potential drug against GBM.

Emergency Obstetric Hysterectomy, the Histopathological Perspective: A Cross-Sectional Study From a Tertiary Care Hospital.

Introduction Emergency obstetric hysterectomy (EOH) is a life-saving procedure which involves the surgical removal of uterus and is usually performed for uncontrollable maternal hemorrhage when all other conservative management has failed. This study was conducted to evaluate the histopathological findings in the EOH specimen received in the department of pathology. Methods This hospital-based cross-sectional study was conducted in the Histopathology Laboratory, Department of Pathology, and Dow Medical College (DMC) from September 2017 to December 2018. The histopathological findings in the EOH specimen were recorded and data was analyzed. Results Ninety-six cases of EOH were received. The incidence of emergency obstetric hysterectomy was 58.37/10,000 deliveries. The mean age of patients was 30.59 years (range 20-45 years). The main histopathological findings were placenta accreta spectrum in 61 (63.54%) cases, cervical tear in eight (8.33%), uterine rupture in seven (7.29%) and endomyometritis in six (6.25%) cases. In the placenta accreta spectrum, placenta accreta was the most frequent diagnosis in 23 (23.96%) of cases, placenta increta in 17 (17.71%), placenta percreta in 10 (10.42%) cases. Seven (7.29%) cases of placenta percreta and four (4.17%) cases of placenta accreta were diagnosed in association with placenta previa. Twenty placentas were received with the hysterectomies, of these eight (40%) placentas showed infarction and six (30%) had intervillous fibrin, both findings were suggestive of uteroplacental insufficiency, while three (15%) placentas had normal histology. Ovaries were received with the hysterectomies in 11 (11.46%) cases. Mature cystic teratoma was diagnosed in two (2.08%) ovaries while the majority of ovaries were normal on histology. Conclusion Placenta accreta spectrum is the leading histopathological finding in the EOH specimen. Regular antenatal follow-up and radiological examination of pregnant women is inferred to prevent obstetric complications and near-miss event of EOH. Further research is recommended to confirm the findings in placenta. Ovarian conservation is suggested in patients undergoing EOH with no clinical and surgical indication for oophorectomy.

Reliability and Validity of WATCH: Warwick Assessment InsTrument for Clinical TeacHing.

OBJECTIVE: To determine the reliability, validity, feasibility, acceptability and perceived educational impact of WATCH: Warwick Assessment insTrument for Clinical teacHing among doctors in Pakistan. STUDY DESIGN: Cross-sectional research study. PLACE AND DURATION OF STUDY: The College of Physicians and Surgeons, Pakistan, from September 2018 to August 2019. METHODOLOGY: Postgraduate trainees were asked to rate the clinical teaching sessions, using WATCH, which consists of 15 items. Percentage was used to calculate gender and participation from different specialties. Inter-item correlations of 15 items with individual mean scores, standard deviations and Cronbach's Alpha were reported, including Friedman test, in order to observe the scores across multiple conditions. The Hotelling's T2 test was used to test whether the answers provided by the study participants to the questionnaire were equal. Construct validity was determined using factor analysis while feasibility, acceptability, and educational impact was evaluated by seeking participants' feedback on five semi-structured questions. RESULTS: More than 80% ranked WATCH from good to excellent.  Oveall 8 items were perceived as excellent, while 7 items received rating of good. Inter-item correlation ranged from 0.61 to 0.81. Cronbach Alpha was reported to be 0.975, with significant difference in mean scores of different items (Friedman's Chi-Square=4285.54; p<0.001). The Hotelling's T2 test (21598.871 with F=185.249, df=14,2654; p<0.001) indicated that the mean values of the responses of different questions in the instrument were statiscally different. Factor analysis indicated one factor accounting for 73.97 of variance. The majority (93%) of the participants found the instrument easy to complete, most participants (91.5%) indicated it as an acceptable method of assessment, and majority (90.8%) perceived that it can improve clinical teaching. CONCLUSION: WATCH demonstrated valid, reliable, feasible, and acceptable results for assessment of teaching of medical doctors and it can be used for providing feedback and rewarding teachers who excel in teaching. Key Words: Clinical teaching, Validity, Reliability, Feasibility, Medical students, Residents, Doctors.

Hysterectomy and Oophorectomy in Reproductive Age: A Cross-Sectional Study from a Tertiary Care Hospital.

Introduction Hysterectomy is a common surgical procedure in women, and oophorectomy may also be performed with the hysterectomy. The objective of this study was to identify clinical indications and pathological findings in hysterectomies, performed for gynecological causes, in women of reproductive age (15-49 years) and to determine if oophorectomy or ovarian conservation was performed with the hysterectomy as well as the pathological findings in the ovaries. Methods This cross-sectional study was conducted in the department of Pathology at Dow Medical College in Karachi, Pakistan, from September 2017 to December 2018. Data were recorded from the pathology reports of hysterectomy specimens received in the department. Data of hysterectomies performed for gynecological causes in women of reproductive age group were selected and analyzed, using Microsoft Excel (Microsoft, Redmond, Washington) and SPSS version 20 (IBM Corp., Armonk, New York). Data of women more than 49 years and obstetric hysterectomies were excluded. Results Three hundred sixty-one hysterectomies were received; 157 of which were hysterectomies performed in women of reproductive age for gynecological reasons. The mean age of the women was 40.37 (± 5.47) years. Abnormal uterine bleeding was the most frequent clinical indication for hysterectomy in 81 (51.59%) women, followed by uterine prolapse in 29 (18.47%) and leiomyoma in 22 (14.01%). Common pathologies in the endometrium were endometritis in 14 (8.92%) and endometrial polyp in nine (5.73%). In the myometrium, leiomyoma was reported in 52 (33.12%) cases, adenomyosis in 37 (23.57%), and both leiomyoma and adenomyosis in 37 (23.57%) women. Uterine prolapse was histologically identified in 38 (24.20%) women. Oophorectomy was performed on 107 (68.15%) women, and out of these, 83 (77.59%) women's ovaries showed either normal histology or functional cysts. Ovarian pathologies reported were endometriosis, serous cystadenomas and oophoritis in five patients each (4.81%), ovarian serous carcinoma in three (2.88%), and mucinous carcinoma in one (0.96%) patient. Conclusion Abnormal uterine bleeding was the most common clinical indication for hysterectomy in women of reproductive age. The common pathologies in the hysterectomies were endometritis, endometrial polyp, leiomyoma, adenomyosis, and uterine prolapse. Most of the ovaries removed with the hysterectomy did not show any significant pathology, therefore, further studies in this direction are recommended for confirmation of this finding. Ovarian conservation may be considered in women undergoing hysterectomy for abnormal uterine bleeding or other uterine causes and with no radiological or surgical indication for oophorectomy.

Using Multiple Mini-Interviews for Students' Admissions in Pakistan: A Pilot Study.

BACKGROUND: A significant challenge continuing to face medical educators is the development of an effective method for student admissions into medical school. Conventional interviews have been commonly used for assessment of non-cognitive skills; however, they are subject to different biases and lack of standardization. The present study aims to determine the validity, reliability, feasibility, and acceptability of implementing Multiple Mini-Interviews (MMI) as a selection method for undergraduate medical students. METHODS: MMI consisting of 8 stations was developed and implemented. A variance component analysis was computed to identify different sources of variance and estimate overall reliability. Content validity was established by seeking consensus on non-cognitive attributes desired by stakeholders. Acceptability and feasibility were determined by a post-MMI questionnaire. RESULTS: A total of 381 out of 450 (84.66%) candidates participated in the study. The G coefficient was 0.70. Participants found MMI as an acceptable and feasible method of assessment, with 75% of candidates and 95% of assessors preferring MMI to traditional interviews. CONCLUSION: MMI as an assessment method for students' admissions demonstrated reliable findings. Stakeholders found it feasible and acceptable. Individual institutions can tailor the stations towards selection of the characteristics that are most valued within their local context.

Medical Students' Perceptions of Clinical Teachers as Role Model.

INTRODUCTION: Role models facilitate student learning and assists in the development of professional identity. However, social organization and cultural values influence the choice of role models. Considering that the social organization and cultural values in South East Asia are different from other countries, it is important to know whether this affects the characteristics medical students look for in their role models in these societies. METHODS: A 32 item questionnaire was developed and self-administered to undergraduate medical students. Participants rated the characteristics on a three point scale (0 = not important, 1 = mildly important, 2 = very important). One way ANOVA and student's t-test were used to compare the groups. RESULTS: A total of 349 (65.23%) distributed questionnaires were returned. The highest ranked themes were teaching and facilitating learning, patient care and continuing professional development followed by communication and professionalism. Safe environment and guiding personal and professional development was indicated least important. Differences were also observed between scores obtained by males and females. CONCLUSION: Globally there are attributes which are perceived as essential for role models, while others are considered desirable. An understanding of the attributes which are essential and desirable for role models can help medical educators devise strategies which can reinforce those attributes within their institutions.

Gestational diabetic transcriptomic profiling of microdissected human trophoblast.

Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is influenced by the placenta, and its prevalence directly increases with obesity. Therefore, to define the aetiology of GDM requires that the confounding influence of obesity and the heterogeneous nature of the placenta impairing accurate quantitative studies be accounted for. Using laser capture microdissection (LCM), we optimized RNA extraction from human placental trophoblast, the metabolic cellular interface between mother and foetus. This allowed specific transcriptomic profiling of trophoblast isolated from GDM, and obese and normal human placentae. Genome-wide gene expression analysis was performed on the RNA extracted from the trophoblast of GDM and obese and normal placentae. Forty-five differentially expressed genes (DEGs) specifically discriminated GDM from matched obese subjects. Two genes previously linked with GDM, pregnancy specific beta-1 glycoprotein 6 (PSG6) and placental system A sodium-dependent transporter system (SLC38A1), were significantly increased in GDM. A number of these DEGs (8 ubiquitin-conjugating enzymes (UBE) splice variants (UBE2D3 variants 1, 3, 4, 5, 6, 7, and 9) and UBE2V1 variant 4)) were involved in RNA processing and splicing, and a significant number of the DEGs, including the UBE variants, were associated with increased maternal fasting plasma glucose.It is concluded that DEGs discriminating GDM from obese subjects were pinpointed. Our data indicate a biological link between genes involved in RNA processing and splicing, ubiquitination, and fasting plasma glucose in GDM taking into account obesity as the confounder.

WATCH: Warwick Assessment insTrument for Clinical teacHing: Development and testing.

OBJECTIVE: Medical education and teaching skills are core competencies included in the generic curriculum for specialty training. To support the development of these skills, there is need for a validated instrument. This study aims to develop and test an instrument to measure the attributes of specialty trainees as effective teachers. METHODS: The study was conducted in two phases. In first phase, the content of the instrument was generated from the literature and tested using the Delphi technique. In second phase, the instrument was field tested for validity and reliability using factor analysis and generalizability study. Feasibility was calculated by the time taken to complete the instrument. Acceptability and educational impact were determined by qualitative analysis of written feedback. Attributes of specialty trainees were assessed by clinical supervisors, peers, and students. RESULTS: The Delphi study produced consensus on 15 statements which formed the basis of the instrument. In field study, a total of 415 instruments were completed. Factor analysis demonstrated a three-factor solution ('learning-teaching milieu', 'teaching skills', and 'learner-orientated'). A generalizability coefficient was 0.92. Mean time to complete the instrument was five minutes. Feedback indicated that it was an acceptable and useful method of assessment. CONCLUSION: This new instrument provides valid, reliable, feasible, and acceptable assessment of clinical teaching.

Elevated soluble CD163 in gestational diabetes mellitus: secretion from human placenta and adipose tissue.

Recently soluble CD163 (sCD163), a cleaved form of the macrophage receptor CD163, was identified as a macrophage-specific risk-predictor for developing Type 2 Diabetes. Here, we investigate circulating levels of sCD163 in gestational diabetes mellitus (GDM). Furthermore, given the role of the placenta in the pathogenesis of GDM, we assessed placental contribution to sCD163 secretion. Paired maternal (venous) and umbilical vein blood samples from GDM (n = 18) and Body Mass Index (BMI) matched control women (n = 20) delivered by caesarean section at 39-40 week gestation were assessed for circulating levels of sCD163, Tumour necrosis factor alpha (TNF-α) and Interleukin 6 (IL-6). Media from explant culture of maternal subcutaneous fat and corresponding placental tissues were assayed for these same molecules. CD163 positive cell numbers were determined in placental and adipose tissues of GDM and control women. We found significantly elevated circulating sCD163 levels in GDM mothers (688.4±46.9 ng/ml vs. 505.6±38.6 ng/ml) and their offspring (418.2±26.6 ng/ml vs. 336.3±24.4 ng/ml [p<0.05 for both]) as compared to controls, together with elevated circulating TNF-α and IL-6 levels. Moreover, both GDM placentae (268.1±10.8 ng/ml/mg vs. 187.6±20.6 ng/ml/mg) and adipose explants (41.1±2.7 ng/ml/mg vs. 26.6±2.4 ng/ml/mg) released significantly more sCD163 than controls. Lastly, significantly more CD163 positive cells were observed in GDM placentae (25.7±1.1 vs. 22.1±1.2) and adipose tissue (19.1±1.1 vs 12.7±0.9) compared to controls. We describe elevated sCD163 levels in GDM and identify human placenta as a novel source of sCD163 suggesting that placental tissues might contribute to the increased levels of circulating sCD163 in GDM pregnancies.