Kisspeptin and attributes of infertile males and females: A cross-sectional study in a subset of Pakistani population

Kisspeptin, a peptide hormone, plays a pivotal role in fertility and neuroendocrine regulation of hypothalamo-pituitary-gonadal axis. Increased kisspeptin and reproductive hormones are responsible for fertility in male and females. This study aimed to explore the role of kisspeptin on hypothalamo-pituitary-gonadal axis by comparing the levels of kisspeptin in fertile and infertile subjects and identifying single nucleotide polymorphisms (SNPs) of KISS1 gene in exon 2 and exon 3 of infertile male and female cohorts. A cross-sectional study was carried out on 80 males (44 infertile and 36 fertile) and 88 females (44 in each group). Significantly high levels of kisspeptin (KP), follicle-stimulating hormone (FSH), luteinizing hormone and testosterone were observed in fertile male and female subjects except low FSH levels in comparison with infertile female subjects. One polymorphism in exon 2 (E1225K [G/A 3673]) and three in exon 3 (P1945A [C/G 5833]; Insertion of T at 6075; G2026G [C/G 6078]) in infertile group were detected, with low KP and hormonal levels. Male subjects had abnormal sperm parameters and unsuccessful attempt of intracytoplasmic sperm injection in females. Expression of SNP in exon 2 and exon 3 of KISS1 could be responsible for alteration in release of reproductive hormones and gonadal functions, hence causing infertility

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Altered sperm parameters and subclinical hypothyroidism; a cross sectional study in Karachi, Pakistan

Objective: The purpose of this study is to compare the thyroid hormone (TH) profile in male infertile subjects with normal and altered sperm parameters and assess its relationship with spermogram and reproductive hormones.Design: This cross-sectional study was conducted in Karachi from August 2017 till September 2018 on three hundred and seventy-six male subjects between 25 to 55 years of age. The reference values for the Normal Sperm Parameters group was; sperm count (TC) \u3e39 million per ejaculate, total sperm motility (Progressive and Non-progressive) \u3e 40%, and normal morphology of ≥ 4%. Male subjects, having any one of the sperm parameters below the reference values comprised the group of Altered Sperm Parameters .The thyroid profile; Thyroxine (T4,) triiodo thyronine (T3), thyroid Stimulating Hormone (TSH), Thyroid Peroxidase antibodies (Anti-TPO) was estimated in addition to reproductive hormones Testosterone and Sex hormone binding globulin (SHBG). Independent sample T test and Analysis of Variance was applied for comparison of groups. Linear regression was performed and unadjusted and adjusted beta coefficient with 95% CI was reported. A p-value of \u3c 0.05 was considered significant.Results: Two hundred and sixteen subjects had normal, whereas one hundred and sixty had \u27Abnormal Sperm Parameters\u27. In \u27Normal Sperm Parameter\u27 group; two hundred and six (95.3%) were euthyroid while ten (4.6%) were having subclinical hypothyroidism (SCH). Amongst the \u27Abnormal Sperm Parameters\u27 group; eighty-seven (54%) subjects were euthyroid, sixty-two (38.75%) had SCH and eleven (6.8%) were having overt hypothyroidism. Testosterone and SHBG were significantly lower in \u27Altered Sperm Parameters\u27 group as compared to \u27Normal Sperm Parameters\u27 (p\u3c0.001 for both).Conclusion: A higher frequency of SCH, decreased levels of testosterone and SHBG was observed in the \u27Altered Sperm Parameters group. The results establish relationship of disturbance in TH with alteration of sperm parameters and reproductive hormones thus contributing to male infertility

PREVALENCE OF MULTI-DRUG RESISTANT BACTERIAL GASTROENTERITIS IN KARACHI, PAKISTAN

Multidrug resistant Escherichia coli (E. coli) associated diarrheal diseases are the most prevalent health problems in Karachi, Pakistan. The main objective of the present study was to evaluate the clinical experiences of individuals suffered from gastroenteritis and also to determine the prevailing sensitivity / resistance pattern of E. coli among the population of Karachi. A cross-sectional retrospective survey was conducted by distributing questionnaires to a total of 150 individuals in December, 2014. The data collected from the questionnaire was statistically analyzed. Majority of the surveyed population was found to be infected by gastroenteritis lately or sometime in their life. On asking the questions about the possible reasons for being infected, it was revealed that the use of untreated water was the major source for the occurrence of the infection. Diagnostic tests were not carried out in most of the cases. Evaluation of questionnaire also indicated that physicians prescribed 2nd line of drug therapy due to the failure of treatment by cephalosporins, quinolones and fosfomycin. The susceptibility pattern of E. coli against selective antimicrobials agents was determined by using disc diffusion method. A total of 50 non-duplicate isolates of bacteria were collected from clinical laboratory of tertiary care hospital. The results were evaluated according to the guidelines of Clinical and Laboratory Standards Institute (CLSI). The findings of sensitivity determination supported the retrospective data indicating that cefexime and ceftriaxone failed to inhibit the growth of 80% of the bacterial sample while ciprofloxacin was also found to be less effective since 65% of the isolates showed resistance to it. A 50% resistance pattern was observed against cefoperazone and sulbactam. The most effective antibiotic against E. coli was found to be colistin (100% sensitive) followed by amikacin (90%), merepenem (90%) and gentamicin (70%). Hence, the in-time monitoring of infection through diagnostic procedures is suggested to avoid treatment failure

Forensic Dentistry In Dire Need Of Recognition As A Separate Entity In Pakistan: A Cross-Sectional Study

Introduction: In this period of advancement, forensic dentistry plays crucial role in recognition of a person for ethical and the legal proceedings through the analysis of orofacial and dental characteristics with previous records. In this study, we aimed to assess the interest of dental professionals in participating in forensic dentistry courses and their willingness to introduce this subspecialty in the course curriculum of post graduate studies and to assess the knowledge, attitude and awareness about forensic odontology among dental professionals of Karachi, Pakistan. Methodology: This cross-sectional study was conducted through an online self-administered Knowledge, Attitude, and Practices (KAP) questionnaire with multiple close-end questions. In a convenient sample of 277 participants that includes academic faculty, undergraduates, postgraduates, house officers, dental care professional students (DCP) and dental technician/hygienist from Karachi, Pakistan. Data was measured using IBM SPSS version 26.0. Results: The survey showed that a significant number of study participants have knowledge of forensic dentistry as a branch 70.02% (p value 0.000) of the respondents showed interest to integrate forensic dentistry in the core curriculum. 62% of the Participants showed willingness to opt forensic dentistry as a career or profession. Those who were unwilling had various reasons. A significant number of people maintain dental records (P value = 0.026). Conclusion: There is need for up gradation and recognition of forensic dentistry into the curricula of dentistry to meet the international trends and pursue it as career

Polymorphism of the renalase gene in gestational diabetes mellitus

Renalase is considered as a novel candidate gene for type 2 diabetes. In this study, we aimed to investigate the relationship of serum renalase and two single nucleotide polymorphisms with gestational diabetes mellitus. One hundred and ninety-eight normotensive pregnant females (n=99 gestational diabetes mellitus; n=99 euglycemic pregnant controls) were classified according to the International Association of the Diabetes and Pregnancy Study criteria. Fasting and 2-h post glucose load blood levels and anthropometric assessment was performed. Serum renalase was measured using enzyme-linked immunosorbent assay, whereas DNA samples were genotyped for renalase single nucleotide polymorphisms rs2576178 and rs10887800 using Polymerase chain reaction-Restriction fragment length polymorphism method. In an age-matched case control study, no difference was observed in the serum levels of renalase (p\u3e0.05). The variant rs10887800 showed an association with gestational diabetes mellitus and remained significant after multiple adjustments (p\u3c0.05), whereas rs2576178 showed weak association (p=0.030) that was lost after multiple adjustments (p=0.09). We inferred a modest association of the rs10887800 polymorphism with gestational diabetes. Although gestational diabetes mellitus is self-reversible, yet presence of this minor G allele might predispose to metabolic syndrome phenotypes in near the future