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Among several known RNA modifications, N6‐methyladenosine (m6A) is the most studied RNA epitranscriptomic modification and controls multiple cellular functions during development, differentiation, and disease. Current research advancements have made it possible to examine the regulatory mechanisms associated with RNA methylation and reveal its functional consequences in the pathobiology of many diseases, including heart failure. m6A methylation has been described both on coding (mRNA) and non-coding RNA species including rRNA, tRNA, small nuclear RNA and circular RNAs. The protein components which catalyze the m6A methylation are termed methyltransferase or 'm6A writers'. The family of proteins that recognize this methylation are termed 'm6A readers' and finally the enzymes involved in the removal of a methyl group from RNA are known as demethylases or 'm6A erasers'. At the cellular level, different components of methylation machinery are tightly regulated by many factors to maintain the m6A methylation dynamics. The m6A methylation process impacts different stages of mRNA metabolism and the biogenesis of long non-coding RNA and miRNA. Although, mRNA methylation was initially described in the 1970s, its regulatory roles in various diseases, including cardiovascular diseases are broadly unexplored. Recent investigations suggest the important role of m6A mRNA methylation in both hypertrophic and ischaemic heart diseases. In the present review, we evaluate the significance of m6A methylation in the cardiovascular system, in cardiac homeostasis and disease, all of which may help to improve therapeutic intervention for the treatment of heart failure. RNA methylation in cardiovascular diseases: altered m6A RNA (coding and non-coding RNA) methylation is identified during different cardiovascular diseases. Increased cardiac hypertrophy is observed following METTL3 overexpression. In contrast, reduced FTO level was seen in mice following myocardial infarction. Increased cardiac fibroblasts activation or increased atherosclerotic plaques were also co-related with m6A RNA methylation. [ABSTRACT FROM AUTHOR]

Background: Urinary incontinence (UI) presents in over 50% menopausal women affecting their quality of life leading to depression and hence needs addressal and treatment as very few of them seek medical help. Aims: Our aim was to determine the prevalence of depression, and the correlation of severity of UI with depression in incontinent women versus continent controls. Methodology: A cross-sectional case–control study of previously diagnosed 100 incontinent women (Stress/Urgency/Mixed) was done over a period of 3 months. The severity of UI was assessed on Patient Incontinence Severity Assessment (a form of Likert scale) and depression was assessed on a validated Patient Health Questionnaire-9 scale. Statistical Analysis: The statistical analysis was performed using SPSS version 19.0. Results: Most of our cases were 51–60 years, with Urge UI being the most predominant (88%). Hundred percent of our incontinent patients were depressed, with 48% and 45% being severely and moderately severely depressed, respectively. A highly significant correlation was found between the severity of incontinence, amount of leakage, leaking pattern, and depression. Conclusion: All of our incontinent patients were depressed, with the severity of depression increasing with the severity of incontinence. [ABSTRACT FROM AUTHOR]

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Klippel--Trenaunay syndrome (KTS) is a rare congenital disorder characterized by the presence of vascular naevi, varicose veins and soft tissue or bone hypertrophy affecting one or more extremities. Due to the rarity of the syndrome, there is limited literature regarding the current practice in the management of pregnancy complicated with KTS. Successful management of pregnancy with KTS is a challenge for clinicians as pregnancy exacerbates the already increased risk of thrombosis and haemorrhage associated with this syndrome. We report a patient with KTS with previous poor obstetric history managed with favourable maternal and foetal outcomes. [ABSTRACT FROM AUTHOR]

Palmitoylation has been recently identified as an important post-translational rheostat for controlling protein function in eukaryotes. However, the molecular machinery underlying palmitoylation remains unclear in the neglected tropical parasite, Leishmania donovani. Herein, we have identified a catalog of 20 novel palmitoyl acyltransferases (PATs) and characterized the promastigote-specific PAT (LdPAT4) containing the canonical Asp-His-His-Cys (DHHC) domain. Immunofluorescence analysis using in-house generated LdPAT4-specific antibody demonstrated distinct expression of LdPAT4 in the flagellar pocket of promastigotes. Using metabolic labeling-coupled click chemistry method, the functionality of this recombinant enzyme could be authenticated in E. coli strain expressing LdPAT4-DHHC domain. This was evident by the cellular uptake of palmitic acid analogs, which could be successfully inhibited by 2-BMP, a PAT-specific inhibitor. Using CSS-Palm based in-silico proteomic analysis, we could predict up to 23 palmitoylated sites per protein in the promastigotes, and further identify distinctive palmitoylated protein clusters involved in microtubule assembly, flagella motility and vesicular trafficking. To highlight, proteins such as Flagellar Member proteins (FLAM1, FLAM5), Intraflagellar Transport proteins (IFT88), and flagellar motor assembly proteins including the Dynein family were found to be enriched. Furthermore, analysis of global palmitoylation in promastigotes using Acyl-biotin exchange purification identified a set of S-palmitoylated proteins overlapping with the in-silico proteomics data. The attenuation of palmitoylation using 2-BMP demonstrated several phenotypic alterations in the promastigotes including distorted morphology, reduced motility (flagellar loss or slow flagellar beating), and inefficient invasion of promastigotes to host macrophages. These analyses confirm the essential role of palmitoylation in promastigotes. In summary, the findings suggest that LdPAT4 acts as a functional acyltransferase that can regulate palmitoylation of proteins involved in parasite motility and invasion, thus, can serve as a potential target for designing chemotherapeutics in Visceral Leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is defined as a carbohydrate intolerance first diagnosed in pregnancy and may be associated with adverse maternal and perinatal outcome. Aim: The aim of the study was to determine the maternal and perinatal outcome in GDM during pregnancy. Materials and Methods: It is a retrospective analysis of women diagnosed with GDM who got antenatal care and delivered in our hospital in previous 5 years. Another 191 women with normal pregnancy without GDM and other medical conditions were taken as control. The baseline characteristics (age, body mass index, religion, and socioeconomic status) were noted in all cases. Diagnosis of GDM was made using oral glucose tolerance test with 75 g glucose. GDM patients were started on diet following which insulin or oral hypoglycemic agents were given if required. Maternal and perinatal outcome was noted in all women. Results: The prevalence of GDM was 5.72% (170/2970). Most patients (79.41%) could be controlled on diet alone. However, 21 (12.35%) needed insulin and 14 (8.23%) needed oral hypoglycemic agents. Middle socioeconomic status was more common in GDM than control and pregnancy-induced hypertension was more common in GDM (13.5%) than in control (6.3%) (P = 0.019). Mode of delivery was not different in two groups. Instrumental deliveries and postpartum hemorrhage were also similar. However, mean birth weight was significantly higher in GDM (2848 ± 539 g) than in control (2707 ± 641 g) (P = 0.004). Incidence of large-for-date babies was also higher (28.2%) in GDM than control (19.4%) (P = 0.005). In neonatal complication, hypoglycemia was significantly higher in GDM (20.6%) than in control (5.2%) (P = 0.001). However, the incidence of hyperbilirubinemia and congenital malformations was not significantly different in two groups. Conclusion: The prevalence of GDM was 5.72% in this study. Adequate treatment of GDM on diet, oral hypoglycemic agents, or insulin to achieve euglycemia can achieve near-normal maternal and neonatal outcome. [ABSTRACT FROM AUTHOR]