An Integrated System for Fetal Scalp Visualization,Blood Collection and Analysis

The Journal of Obstetrics and Gynecology of India - The new NB scope aids in better visualization of the scalp and blood collection and analysis at bed side. Caesarean section rates and inherent...     

Neutrophil Extracellular Traps Promote NLRP3 Inflammasome Activation and Glomerular Endothelial Dysfunction in Diabetic Kidney Disease

Diabetes mellitus is a metabolic disease largely due to lifestyle and nutritional imbalance, resulting in insulin resistance, hyperglycemia and vascular complications. Diabetic kidney disease (DKD) is a major cause of end-stage renal failure contributing to morbidity and mortality worldwide. Therapeutic options to prevent or reverse DKD progression are limited. Endothelial and glomerular filtration barrier (GFB) dysfunction and sterile inflammation are associated with DKD. Neutrophil extracellular traps (NETs), originally identified as an innate immune mechanism to combat infection, have been implicated in sterile inflammatory responses in non-communicable diseases. However, the contribution of NETs in DKD remains unknown. Here, we show that biomarkers of NETs are increased in diabetic mice and diabetic patients and that these changes correlate with DKD severity. Mechanistically, NETs promote NLRP3 inflammasome activation and glomerular endothelial dysfunction under high glucose stress in vitro and in vivo. Inhibition of NETs (PAD4 inhibitor) ameliorate endothelial dysfunction and renal injury in DKD. Taken together, NET-induced sterile inflammation promotes diabetes-associated endothelial dysfunction, identifying a new pathomechanism contributing to DKD. Inhibition of NETs may be a promising therapeutic strategy in DKD.     

Bortezomib,Lenalidomide and Dexamethasone Combination Induced Complete Remission in Relapsed/Refractory Plasmablastic Lymphoma: Case Report of a Potential Novel Treatment Approach

Plasmablastic lymphoma is a rare subtype of large B-cell lymphoma characterised by an aggressive clinical course with frequent relapses and refractoriness to chemotherapy. It is usually associated with HIV, however, it can also be seen in immunocompetent patients. It has distinct pathological characteristics, such as plasmablastic morphology and lack of CD20 expression. These characteristics pose a clinical and pathological challenge. There is no standard of care established in this entity. In this case report, we described a novel bortezomib-based plasma cell targeted regimen in a HIV-negative patient refractory to chemotherapy.     

Exploiting the power of LINE-1 retrotransposon mutagenesis for identification of genes involved in embryonic stem cell differentiation

Identifying the genes or epigenetic factors that control the self-renewal and differentiation of stem cells is critical to understanding the molecular basis of cell commitment. Although a number of insertional mutagenesis vectors have been developed for identifying gene functions in animal models, the L1 retrotransposition system offers additional advantages as a tool to disrupt genes in embryonic stem cells in order to identify their functions and the phenotypes associated with them. Recent advances in producing synthetic versions of L1 retrotransposon vector system and the optimization of techniques to accurately identify retrotransposon integration sites have increased their utility for gene discovery applications. We have developed a novel episomal, nonviral L1 retrotransposon vector using scaffold/matrix attachment regions that provides stable, sustained levels of retrotransposition in cell cultures without being affected by epigenetic silencing or from some of the common problems of vector integration. This modified vector contains a GFP marker whose expression occurs only after successful gene disruption events and thus the cells with disrupted genes can be easily picked for functional analysis. Here we present a method to disrupt gene function in embryonic stem cells that aid in the identification of genes involved in stem cell differentiation processes. The methods presented here can be easily adapted to the study of other types of cancer stem cells or induced pluripotent stem cells using the L1 retrotransposon as an insertional mutagen.     

Therapeutic Hypothermia Using Gel Packs for Term Neonates with Hypoxic Ischaemic Encephalopathy in Resource-limited Settings: a Randomized Controlled Trial

Objective: To evaluate the efficacy of therapeutic hypothermia (TH) using gel packs in reducing mortality and morbidity in term neonates with HIE and study the associated problems with TH. Methods: Hypoxic ischaemic encephalopathy babies were randomized into TH and control group. Babies in TH group were cooled for first 72?h of birth using cloth covered cooling gel packs to maintain target rectal temperature of 33-34°C. Infants were followed up to 6 months and were assessed using Baroda Developmental Screening Test. Results: There were no significant differences in baseline parameters. TH group showed significant reduction in the combined rate of death or developmental delay at 6 months of age by 21% (8.1% in the TH group vs. 29% in the control, RR 0.28, 95% CI: 0.11-0.70; p?=?0.003). Conclusions: TH using gel packs reduces the risk of death or developmental delay at 6 months of age in infants with HIE. Trial registration number: CTRI/2011/06/001780.     

Effect of Advanced Glycation End-Products (AGE) Lowering Drug ALT-711 on Biochemical,Vascular, and Bone Parameters in a Rat Model of CKD-MBD

Chronic kidney disease–mineral bone disorder (CKD-MBD) is a systemic disorder that affects blood measures of bone and mineral homeostasis, vascular calcification, and bone. We hypothesized that the accumulation of advanced glycation end-products (AGEs) in CKD may be responsible for the vascular and bone pathologies via alteration of collagen. We treated a naturally occurring model of CKD-MBD, the Cy/+ rat, with a normal and high dose of the AGE crosslink breaker alagebrium (ALT-711), or with calcium in the drinking water to mimic calcium phosphate binders for 10 weeks. These animals were compared to normal (NL) untreated animals. The results showed that CKD animals, compared to normal animals, had elevated blood urea nitrogen (BUN), PTH, FGF23 and phosphorus. Treatment with ALT-711 had no effect on kidney function or PTH, but 3 mg/kg lowered FGF23 whereas calcium lowered PTH. Vascular calcification of the aorta assessed biochemically was increased in CKD animals compared to NL, and decreased by the normal, but not high dose of ALT-711, with parallel decreases in left ventricular hypertrophy. ALT-711 (3 mg/kg) did not alter aorta AGE content, but reduced aorta expression of receptor for advanced glycation end products (RAGE) and NADPH oxidase 2 (NOX2), suggesting effects related to decreased oxidative stress at the cellular level. The elevated total bone AGE was decreased by 3 mg/kg ALT-711 and both bone AGE and cortical porosity were decreased by calcium treatment, but only calcium improved bone properties. In summary, treatment of CKD-MBD with an AGE breaker ALT-711, decreased FGF23, reduced aorta calcification, and reduced total bone AGE without improvement of bone mechanics. These results suggest little effect of ALT-711 on collagen, but potential cellular effects. The data also highlights the need to better measure specific types of AGE proteins at the tissue level in order to fully elucidate the impact of AGEs on CKD-MBD. © 2019 American Society for Bone and Mineral Research.     

Isolation, characterization, antibacterial, antihelminthic, and in silico studies of polyprenol from Kirganelia reticulata Baill

Microbial and helminthes infections are the most common health problems in India; in developing countries they pose a large treat to public. These infections can affect most population in endemic areas with major economic and social consequences. In vitro antibacterial activity of a phytoconstituent, polyprenol isolated from the leaves of Kirganelia reticulata was screened against Gram-negative and Gram-positive bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) of the purified antibacterial agent were also determined. The present study also undertook evaluation of antihelminthic activity of polyprenol at different concentrations using Pheretima posthuma as a test worm. The bioassay involved the determination of paralysis time and death time of the worm. The polyprenol showed antibacterial activity against different bacterial strains with MIC 6.25–25.0 mgml^?1 and MBC 12.50–25.0 mgml^?1, and possesses better glucosamine-6-phosphate synthase inhibition in molecular docking studies with minimum docking energy and better ligand efficiency when compared to the standard. The antihelminthic results of the present study indicated that polyprenol significantly demonstrated paralysis and caused death of worm in dose-dependent manner; showing comparable results with the standard in docking process. Hence, the isolated compound polyprenol is suggestive of being a good antibacterial and antihelminthic agent.