Prevalence of thyroid dysfunction in patients with polycystic ovarian syndrome: a cross sectional study

Background: Polycystic ovary syndrome (PCOS) and thyroid disorders are two of the most common endocrine disorders in the general population. Both of these endocrine disorders share common predisposing factors, gynaecological features and have profound effect on reproductive function in women. The aim of this study is to study the prevalence of thyroid dysfunction in patients with polycystic ovarian syndrome and to evaluate the relationship between polycystic ovarian syndrome and thyroid dysfunction.Methods: This is a cross sectional observational study done on 100 patients with Poly Cystic Ovarian Syndrome based on Rotterdam’s criteria. The exclusion criteria was hyperprolactinemia, congenital adrenal hyperplasia and virilising tumour. Thyroid function was evaluated by measurement of fasting serum thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4).Results: The mean age of the study patients was 26±4.2 years. Among the study patients, 11% of them had goitre. 18% of the patients with presented with subclinical hypothyroidism. The mean TSH levels in the study patients was 4.62±2.12 mIU/ml. The overall prevalence of thyroid dysfunction was 33% in the study patients with PCOS.Conclusions: This study concludes that the prevalence of hypothyroidism is increased in women with PCOS patients

Clinical and microbiological profile of type 2 diabetic patients with urinary tract infections

Background: Diabetes Mellitus is reported to increase the risk of Urinary Tract Infection (UTI) with higher probability of drug resistant organisms. Understanding the burden, microbiological profile and antibiotic sensitivity pattern is vital for effective prevention and management. To assess the microbiological profile and antibiotic sensitivity pattern of Urinary Tract infections among type 2 diabetes mellitus patients.Methods: The study was A prospective observational study done on 117 type 2 diabetic subjects aged above 18 years presenting with symptoms of UTI in a tertiary care hospital Urine was analyzed for urine routine examination, culture and antibiotic sensitivity using standard testing methods on a midstream urine sample. Descriptive analysis was carried out by mean and standard deviation for quantitative variables, frequency and proportion for categorical variables.Results: The mean age of the study population was 57 years. Females constituted 62.39% of participants. Burning micturition (52.99%) was the most common presenting symptom. The prevalence of culture positive UTI was 51.28%. Among gram-negative bacilli, Escherichia coli (20.51%), Klebsiella (6.85%) dominated the culture reports. Enterococcus (4.27%) and Staphylococcus aureus (2.6%) were the common gram-positive organisms isolated.  Meropenem was the most effective antibiotic against E. coli (87.5%) and Klebsiella (95%) Vancomycin had 100% sensitivity against Enterococci and S. aureus.Conclusions: More than half of diabetic patients presenting with symptoms of UTI had culture positive UTI, predominantly caused by gram negative organisms. There is a need for comparative studies of Diabetes and controls to explore the key differences in the pattern of UTI

Role of diagnostic hystero-laparoscopy in the evaluation of female infertility

Background: Infertility affects about 10-15% of reproductive age couples. The main causes of infertility include male factor, ovulatory disorders, tubal factor and endometriosis. This study was conducted to determine the role of Diagnostic hystero-laparoscopy (DHL) in the evaluation of female infertility.Methods: This study was a prospective study done in a tertiary care centre over a period of 1 year on all infertile couples. The exclusion criteria: male factor infertility, hypothyroidism, hyperprolactinemia, acute pelvic inflammatory disease. Diagnostic hysterolaparoscopy was performed in all study patients in pre ovulatory phase, under general anaesthesia. The findings were then documented and analysed.Results: A total number of 90 patients were recruited for the study. The mean age of the patients was 28±3 years. The mean BMI of the study patients was 25±4 kg/m2. The mean duration of infertility was 5.4 years. On laparoscopy, 28 patients had polycystic ovaries (31.1%), 4 patients had pelvic adhesions (4.4%), 2 patients had endometriosis (2.2%) and tubal block was identified in 10 patients (11.11%). 10 patients had abnormal findings on hysteroscopy.Conclusions: Hystero laparoscopy is an effective diagnostic tool in the evaluation of infertility and has to be included in basic diagnostic workup

The Vicious Cycle Towards Violence: Focus on the Negative Feedback Mechanisms of Brain Serotonin Neurotransmission

Violence can be defined as a form of escalated aggressive behavior that is expressed out of context and out of inhibitory control, and apparently has lost its adaptive function in social communication. Little is known about the social and environmental factors as well as the underlying neurobiological mechanisms involved in the shift of normal adaptive aggression into violence. In an effort to model the harmful acts of aggression and violence in humans, we recently (re)developed an animal model that is focused on engendering uncontrolled forms of maladaptive aggressive behavior in laboratory-bred feral rats and mice. We show that certain (8–12%) constitutionally aggressive individuals gradually develop, over the course of repetitive exposures to victorious social conflicts, escalated (short-latency, high-frequency and ferocious attacks), persistent (lack of attack inhibition by defeat/submission signals and perseverance of the aggressive attack-biting bout), indiscriminating (attacking female and anesthetized male intruders) and injurious (enhanced vulnerable-body region attacks and inflicted wounding) forms of offensive aggression. Based on the neurobiological results obtained using this model, a revised view is presented on the key role of central serotonergic (auto)regulatory mechanisms in this transition of normal aggression into violence

Expression, purification and characterization of a biologically active and thermally stable human lysyl oxidase

Lysyl oxidase (LOX), a promising therapeutic target for the progression of cancer and fibrosis, has not been well characterized yet. A major difficulty faced in LOX characterization is its lack of solubility in common buffers. In this study, mature LOX (mLOX) was cloned, purified and its purity was ascertained by mass spectroscopy. Through screening various buffers, 0.2 M glycine-NaOH buffer with 10% glycerol pH 8.0 was identified to maintain mLOX in its soluble state. About 67% of the refolded mLOX was found to be in copper bound state after His-tag removal. Catalytic properties Km and kcat were found to be 3.72 × 10−4 M and 7.29 ×103s−1. In addition, collagen cross-linking in ARPE-19 cells was augmented on exposure to mLOX, endorsing its biological activity. Circular Dichroism revealed that mLOX comprises 8.43% of α-helix and 22% of β-strand and it was thermally stable up to 90°C. Disulfide linkage imparts the structural stability in LOX which was experimentally ascertained with intrinsic and extrinsic fluorescence studies

Clinico-pathological association of delineated miRNAs in uveal melanoma with monosomy 3/Disomy 3 chromosomal aberrations

PURPOSE: To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort. METHODS: Based on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52). RESULTS: Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated. CONCLUSION: UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment