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The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both first trimester differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to two major placental pathologies, preeclampsia and placenta accreta spectrum, so characterization of the corresponding normal processes is crucial. In this report, our gene expression analysis, using purified human CTB and EVT cells, highlights an epithelial-mesenchymal transition (EMT) mechanism underlying CTB-EVT differentiation and provides a trophoblast-specific EMT signature. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome-wide hypomethylation in the transition to EVT. However, a small subgroup of genes undergoes gains of methylation (GOM) in their regulatory regions or gene bodies, associated with differential mRNA expression (DE). Prominent in this GOM-DE group are genes involved in the EMT, including multiple canonical EMT markers and the EMT-linked transcription factor RUNX1, for which we demonstrate a functional role in modulating the migratory and invasive capacities of JEG3 trophoblast cells. This analysis of DE associated with locus-specific GOM, together with functional studies of an important GOM-DE gene, highlights epigenetically regulated genes and pathways acting in human EVT differentiation and invasion, with implications for obstetric disorders in which these processes are dysregulated.
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OBJECTIVE: To determine the coronavirus disease-2019-related risk perception and altruistic response among undergraduate medical students post-lockdown. Methods: The analytical cross-sectional study was conducted from October 1, 2020, to March 31, 2021, at the Baqai Medical University, Karachi, and comprised undergraduates aged 16 and above, studying in medical, dental, physiotherapy, pharmacy and Information technology departments. Data was collected using a structured and standardised online questionnaire. Positive responses led to a perceived risk score ranging 0-9, with a higher score indicating a greater perception of risk. The score was corelated with demographic variables. Data was analysed using SPSS 21. RESULTS: Of the 743 subjects, 472(63.5%) were females. The overall mean age of the sample was 21.34±1.8 years. The mean risk perception score was 3.8±2.5, and it was significantly associated with disease exposure (p<0.001). Altruism had a strong association with the perceived risk score (p<0.001), indicating lower risk perception. Conclusion: The risk perception among the students was low, pointing towards a need of psychological assistance programme for the students.
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COVID-19 , Estudiantes de Medicina , Femenino , Humanos , Adulto Joven , Adulto , Masculino , Altruismo , Estudios Transversales , COVID-19/epidemiología , Control de Enfermedades Transmisibles , PercepciónRESUMEN
Background: Proton Pump inhibitors are widely used among the majority of the world's population as acid-suppressing medications. Proton Pump Inhibitors have been reported to cause intestinal damage and adverse gut microbiota changes affecting several mechanisms, including malabsorption, etc. Aim: In order to gain a deeper understanding, we conducted a cohort analysis to assess the prevalence & association of Vitamin B12 deficiency in patients on long-term use of PPIs. Methods: This single-center cohort study was conducted at the Department of Internal Medicine, KRL hospital in Islamabad, Pakistan from May 2021 to May 2022. Rao soft calculator with a 95% confidence interval and 5% error margin was used to find the estimated sample size. Vitamin B12 levels were analyzed using the Cobas e411 analyzer. Chi-square test, odds ratio, and t-tests were used for analysis. Results: Among the 1225 participants, more than half of the men (55.10%) had low levels of vitamin B12. Vit B12 levels were observed to be significantly lower in Omeprazole patients than in Pantoprazole patients. A vitamin B12 deficiency is 0.5 times more likely in patients taking PPIs. There is a substantial difference between the early and final levels of B12 indicated by the t-test. Conclusion: According to our findings, long-term usage of PPIs is linked to an increased risk of vitamin B12 insufficiency specifically in men falling under the ages of 18 and 40.
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BACKGROUND: Obesity is increasing rapidly affecting half billion adult's population. Pathophysiology of obesity involves low grade inflammation sustained by Toll like receptor 2 (TLR-2) the innate immune adapters. This study was conducted for detection and association of TLR-2 gene mutations with obesity. METHODS: In this case-control study 228 individuals with obesity and 228 controls were enrolled based on Body Mass Index (BMI) ≥25 and 18-24 kg/m2 respectively. The variations in TLR-2 gene were detected by Sanger sequencing. These identified TLR-2 variants were further analyzed in silico for change in miRNA binding and mRNA strucutre. RESULTS: Four novel single base substitutions (153688371 T >C, 153702295 T >C, 153703504 T >C and 153705074 C >A) were identified in exon 3 and 4 of TLR-2 gene affecting splice site and poly-A tail. The genotypic and allelic frequencies of the variants were strongly associated with increasing obesity susceptibility. Only variant 153703504 T >C was significantly associated with preobesity. Despite variations in gene sequence, no change in miRNA binding except for variant 153688371 T >C of Exon 3 where a novel binding site for hsa-miR-4523 was created. Furthermore, mRNA stability and secondary structure were also compromised in identified variants. CONCLUSION: All detected variants of TLR-2 gene were significantly associated with and posed risk for development of obesity. Furthermore, in silico analysis revealed generation of new miRNA (hsa-miR-4523) binding site and change in mRNA structure/stability which needs to be further investigated for possible role in altering TLR-2 gene regulation/expression in obesity.
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MicroARNs , Receptor Toll-Like 2/metabolismo , Adulto , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Células Germinativas , Humanos , MicroARNs/genética , Obesidad/genética , Pakistán/epidemiología , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , Receptor Toll-Like 2/genéticaRESUMEN
Necrotizing fasciitis (NF) is a rare but life-threatening medical and surgical emergency. It is characterized by necrosis of the soft tissue leaving the overlying tissue unaffected, which delays the diagnosis and treatment. Delay in recognition of the severity of necrotizing fasciitis might lead to serious morbidity and mortality. Diagnosis of NF relies on strong clinical judgment, predictable by severe pain, erythema, and a presence of air under the skin, but all of them are not always present. Management of NF is prompt surgical intervention and antimicrobial therapy. The effectiveness depends on the timely diagnosis of NF because it rapidly spreads and may cause irreversible damage. Various investigations for necrotizing fasciitis have been proposed. However, misdiagnosis is not infrequent and more work is needed to identify the different presentations across the spectrum. We consider changing it to discuss the role of procalcitonin in the diagnosis of necrotizing fasciitis.There is scarce literature about its clinical role in necrotizing fasciitis although it has evolved not only as a prognostic marker but also as a way of differentiating between cellulitis and necrotizing fasciitis. It can also predict the future consequences of septic shock.
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OBJECTIVE: To evaluate the knowledge and attitudes towards handwashing of clinical year medical and dental students and health-care professionals (HCPs) working in the departments of medicine, surgery, dentistry, nursing, and physiotherapy in Lahore, Pakistan. METHODOLOGY: This was a cross-sectional survey conducted during May and June 2016. After approval from the institutional review board, a modified form of the World Health Organization (WHO) Hand Hygiene Knowledge Questionnaire for Healthcare workers that included 18 items was sent to 400 clinical year students and HCPs from six medical colleges and affiliated hospitals of Lahore. The data obtained was entered and analyzed by using IBM SPSS version 20 (IBM, NY, USA). Chi-square was used as the test of significance. A p-value of <0.05 was considered statistically significant for all purposes. RESULTS: The response rate was 79%. Less than half of the respondents (149, 47.9%) were satisfied with their knowledge regarding hand hygiene. Statistically significant associations of various groups of HCPs were observed with their satisfaction regarding knowledge about hand hygiene (p-value = 0.022), their awareness of the proper technique required for handwashing proposed by the WHO (p-value = 0.001), and their awareness about other preventive techniques proposed by the WHO and Centers for Disease Control (CDC) (p-value = 0.021). CONCLUSIONS: The majority of the clinical year students and HCPs were not satisfied with their knowledge regarding hand hygiene. HCPs working in different departments have varying knowledge and attitudes towards hand hygiene. Females were found to be more satisfied with their handwashing practices. Teaching proper technique of handwashing to medical students and starting refresher courses regarding hand hygiene for HCPs are dire needs. The WHO-recommended guidelines should not only be taught but also implemented in the medical field as poor hand hygiene techniques have led to the spread of many diseases around the globe.