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Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting. [ABSTRACT FROM AUTHOR]

Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery in children. Recent studies have implicated SMARCC1 , a component of the BRG1-associated factor (BAF) chromatin remodelling complex, as a candidate congenital hydrocephalus gene. However, SMARCC1 variants have not been systematically examined in a large patient cohort or conclusively linked with a human syndrome. Moreover, congenital hydrocephalus-associated SMARCC1 variants have not been functionally validated or mechanistically studied in vivo. Here, we aimed to assess the prevalence of SMARCC1 variants in an expanded patient cohort, describe associated clinical and radiographic phenotypes, and assess the impact of Smarcc1 depletion in a novel Xenopus tropicalis model of congenital hydrocephalus. To do this, we performed a genetic association study using whole-exome sequencing from a cohort consisting of 2697 total ventriculomegalic trios, including patients with neurosurgically-treated congenital hydrocephalus, that total 8091 exomes collected over 7 years (2016–23). A comparison control cohort consisted of 1798 exomes from unaffected siblings of patients with autism spectrum disorder and their unaffected parents were sourced from the Simons Simplex Collection. Enrichment and impact on protein structure were assessed in identified variants. Effects on the human fetal brain transcriptome were examined with RNA-sequencing and Smarcc1 knockdowns were generated in Xenopus and studied using optical coherence tomography imaging, in situ hybridization and immunofluorescence. SMARCC1 surpassed genome-wide significance thresholds, yielding six rare, protein-altering de novo variants localized to highly conserved residues in key functional domains. Patients exhibited hydrocephalus with aqueductal stenosis; corpus callosum abnormalities, developmental delay, and cardiac defects were also common. Xenopus knockdowns recapitulated both aqueductal stenosis and cardiac defects and were rescued by wild-type but not patient-specific variant SMARCC1. Hydrocephalic SMARCC1-variant human fetal brain and Smarcc1-variant Xenopus brain exhibited a similarly altered expression of key genes linked to midgestational neurogenesis, including the transcription factors NEUROD2 and MAB21L2. These results suggest de novo variants in SMARCC1 cause a novel human BAFopathy we term 'SMARCC1-associated developmental dysgenesis syndrome', characterized by variable presence of cerebral ventriculomegaly, aqueductal stenosis, developmental delay and a variety of structural brain or cardiac defects. These data underscore the importance of SMARCC1 and the BAF chromatin remodelling complex for human brain morphogenesis and provide evidence for a 'neural stem cell' paradigm of congenital hydrocephalus pathogenesis. These results highlight utility of trio-based whole-exome sequencing for identifying pathogenic variants in sporadic congenital structural brain disorders and suggest whole-exome sequencing may be a valuable adjunct in clinical management of congenital hydrocephalus patients. [ABSTRACT FROM AUTHOR]

In order to approximate Lebesgue integrable functions on the positive real axis, we propose an integral variant of Baskakov operators. We show that the linear operators so obtained exhibit the quadratic approximation order $ O(n^{-2}) $ for sufficiently large values of $ n. $ [ABSTRACT FROM AUTHOR]

Sucrose and auxin are well-known determinants of root system architecture (RSA). However, the factors that connect the signaling pathways evoked by these two critical factors during root development are poorly understood. In this study, we report the role of MEDIATOR SUBUNIT17 (MED17) in RSA and its involvement in the transcriptional integration of sugar and auxin signaling pathways in Arabidopsis (Arabidopsis thaliana). Sucrose regulates root meristem activation through the TARGET OF RAPAMYCIN-E2 PROMOTER BINDING FACTOR A (TOR-E2FA) pathway, and auxin regulates lateral root (LR) development through AUXIN RESPONSE FACTOR-LATERAL ORGAN BOUNDARIES DOMAIN (ARF-LBDs). Both sucrose and auxin play a vital role during primary and LR development. However, there is no clarity on how sucrose is involved in the ARF-dependent regulation of auxin-responsive genes. This study establishes MED17 as a nodal point to connect sucrose and auxin signaling. Transcription of MED17 was induced by sucrose in an E2FA/B-dependent manner. Moreover, E2FA/B interacted with MED17, which can aid in the recruitment of the Mediator complex on the target promoters. Interestingly, E2FA/B and MED17 also occupied the promoter of ARF7, but not ARF19, leading to ARF7 expression, which then activates auxin signaling and thus initiates LR development. MED17 also activated cell division in the root meristem by occupying the promoters of cell-cycle genes, thus regulating their transcription. Thus, MED17 plays an important role in relaying the transcriptional signal from sucrose to auxin-responsive and cell-cycle genes to regulate primary and lateral root development, highlighting the role of the Mediator as the transcriptional processor for optimal root system architecture in Arabidopsis. [ABSTRACT FROM AUTHOR]

This article presents a configuration that can simulate both a resistor in series with a frequency-dependent negative-resistance (R-D) and a resistor in series with a capacitor (R-C), with a different selection of passive elements. The proposed circuit employs only two current-controlled-current-feedback-amplifiers (CC-CFAs) and grounded passive elements. This configuration does not require passive element matching, and the simulated equivalent element values can be tuned electronically by applying a biasing current to the CC-CFAs. To demonstrate the application of the proposed grounded series R-D impedance simulator, it is applied to a second-order notch filter and a fifth-order elliptic lowpass filter, whereas the series R-C impedance simulator is applied to a secondorder resonance circuit to find the band-pass response of the input current. Our theoretical analysis is confirmed by the results of a PSPICE simulation. [ABSTRACT FROM AUTHOR]

A series of alkyl‐group‐functionalized, aniline‐ and indoline‐donor‐based, unsymmetrical visible‐light‐active squaraine dyes, AM1‐3, were designed and synthesized. Dye‐sensitized solar cell (DSSC) devices were fabricated with both I−/I3− and [Cu(tmby)2]+/2+ electrolytes. DSSC devices sensitized with the AM1 and AM2 dyes showed relatively high‐power conversion efficiency of 7.44 % and 7.22 %, respectively with I−/I3− in the absence of chenodeoxycholic acid (CDCA) than those of the AM3 dye (5.41 %). The [Cu(tmby)2]+/2+ electrolyte along with poly(3,4‐ethylenedioxythiophene) (PEDOT) as cathode material showed excellent open‐circuit potentials (VOC) of 1030, 1025, and 1001 mV with the DSSC efficiency of 8.05 %, 7.96 %, and 5.84 %, respectively, for the AM1, AM2, and AM3 dyes in the absence of CDCA. Here, the AM1 dye exhibited the maximum DSSC efficiency of 8.05 % and VOC of 1030 mV, which is the highest obtained efficiency and VOC for the visible‐light active zwitterionic unsymmetrical‐squaraine dye with copper‐based electrolyte. [ABSTRACT FROM AUTHOR]

Meeting the UN's zero-hunger goal and achieving food security for the world's growing population with sustainable agriculture is a tough challenge. Besides, using unwarranted amounts of agrochemicals to increase crop productivity often has the downside of unpreventable adverse environmental outcomes. Developed countries have acknowledged this issue and taken constructive steps to minimize ecological nightmares, but developing and underdeveloped economies have yet to address this challenge. More often, farmers' lack of knowledge and awareness about these hazardous chemicals has resulted in their overuse to tackle pre- and post-harvest losses. The use of agrochemicals has increased apparently due to their lower efficacy and loss related to degradation, leaching, pest resistance, etc. Thus, traditional pest-management practices must be reworked to ensure resilience and sustainability. The recent technological innovations in agronomy in terms of sustainable intensification (SI), integrated pest management (IPM), and the emergence of agro-nanotechnology offer plausible solutions by providing viable alternatives without net environmental cost. The bulk of data available on the impact of nanotechnology on agriculture holds promise for its future as a potential approach that could bring about a paradigm shift in conventional crop production. In this framework, control release formulations (CRF) technology can emerge as one of the most valued innovations in modern agriculture. Existing pest management strategies could be improved with a better understanding of the pros and cons of the impact of CRFs on plant responses, including their uptake, localization, and activity. The primary goal of this review is to review the benefits and constraints of extant pest management systems and how CRF could be a possible alternative for wise pesticide usage to minimize health issues and the environment. [ABSTRACT FROM AUTHOR]

Delayed wound healing in patients having type-II diabetes mellitus (T2DM) often results in a high rate of amputation. We report an innovative Guar Gum-based macroporous hydrogel (HG) infused with an antibacterial agent (Ag NPs), and antioxidant, epigallocatechin gallate (EGCG) to address rapid wound healing and interestingly could inhibit the associated pathophysical bone infection in a high-fat-diet-induced T2DM C57BL/6 mice model. The HG-Ag-EGCG elicits scar-free wound healing in subcutaneous wounds and histopathological evidence confirmed HG-Ag-EGCG hydrogel patch elicits better wound healing through enhanced cell proliferation, mature connecting tissue fiber formation, minimum void spaces formation, and better re-epithelialization when compared with a market available hydrogel patch material (Luofucon®). Supportive of the in vivo outcomes, in vitro experiments delineated better-wound closure due to improved management of ROS by the HG-Ag-EGCG. Additionally, a favorable non-toxicity outcome assessed through both in vitro and in vivo conditions confirmed its potential applicability in clinical wound care management. [ABSTRACT FROM AUTHOR]

Background and Purpose: A high-fat diet (HFD) is a common risk factor for Type 2 diabetes mellitus (T2DM) and its associated cognitive impairments. In models of diabetes, resveratrol, a modulator of SIRT1, regulates the fasting glucose and antioxidant levels, as well as the lipid profile. Resveratrol may also alleviate the cognitive dysfunctions associated with diabetes.Experimental Approach: Albino rats were fed a HFD, (60% kcal fat) after treatment with streptozotocin (45 mg·kg-1 ,i.p., single dose) to induce an experimental model of T2DM. After 14 weeks of the animals in confirmed diabetic condition, they were treated with metformin (200 mg·kg-1 ,i.p.) or resveratrol (50 or 100 mg·kg-1 ,i.p.) for 4 weeks. Levels of oxidative-nitroso-stress, SIRT1, TGF-β1, inflammation and cholinergic activity were determined in plasma, hippocampus and cerebral cortex. A battery of behavioural studies associated with learning memory were performed during and after the experimental protocol.Key Results: Treatment with resveratrol attenuated the increased glucose levels (pre- and post-prandial), impaired glucose tolerance, HbA1c, and decreased the body weights of the T2DM rats. Moreover, resveratrol ameliorated the impaired learning and memory associated with increased SIRT1 and decreased TGF-β1, TNF-α, oxidative-nitroso-stress, and cholinergic activities in the plasma and the brains of the T2DM animals.Conclusion and Implication: Our results demonstrated that SIRT1 modulation interacted with TGF-β1 signalling, and mitigated hyperglycaemia and subsequent learning-memory impairments in the T2DM animals. Our study also suggested novel therapeutic targets, including TGF-β1, which may add to our knowledge of resveratrol, when used to treat impaired memory associated with diabetes. [ABSTRACT FROM AUTHOR]

Excision tissue biopsy, while central to cancer treatment and precision medicine, presents risks to the patient and does not provide a sufficiently broad and faithful representation of the heterogeneity of solid tumors. Here we introduce e-biopsy—a novel concept for molecular profiling of solid tumors using molecular sampling with electroporation. As e-biopsy provides access to the molecular composition of a solid tumor by permeabilization of the cell membrane, it facilitates tumor diagnostics without tissue resection. Furthermore, thanks to its non tissue destructive characteristics, e-biopsy enables probing the solid tumor multiple times in several distinct locations in the same procedure, thereby enabling the spatial profiling of tumor molecular heterogeneity.We demonstrate e-biopsy in vivo, using the 4T1 breast cancer model in mice to assess its performance, as well as the inferred spatial differential protein expression. In particular, we show that proteomic profiles obtained via e-biopsy in vivo distinguish the tumors from healthy breast tissue and reflect spatial tumor differential protein expression. E-biopsy provides a completely new molecular sampling modality for solid tumors molecular cartography, providing information that potentially enables more rapid and sensitive detection at lesser risk, as well as more precise personalized medicine. [ABSTRACT FROM AUTHOR]

We use unsupervised machine learning techniques aided by the Gaussian mixture model (GMM) for clustering downhole data of gas hydrate reservoir in the Andaman Sea, where drilling and coring were done at Site 17 in 2006 under the first expedition of the Indian National Gas Hydrate Programme (NGHP-01). Six different logging data (namely; density, neutron porosity, gamma-ray, resistivity, P- and S-wave velocity) are used in this study. We obtain six clusters using Davies-Bouldin index, Calinski-Harabasz index, Dunn index, dendrogram and self-organizing map, which are verified by high silhouette values. Data are then clustered using k-means, principal component analysis (PCA) and GMM. We notice that the k-means with random initialization gets biased towards the dominant principal component (gamma-ray), whereas, PCA shows each log has optimal weightage. Based on statistical analysis using 100 runs, GMM with the k-means initialization provides better results than GMM with random initialization. However, it provides three possible configurations of six clusters, which become stable when a combination of six logs is used as another input. Six clusters are interpreted in terms of lithology by histogram analysis of the corresponding log values. Lithology is found clay-dominated sediments with little silt and sand, as well as scattered volcanic ash, carbonate ooze, and pyrite, which is consistent with the lithology determined by smear slide and sieve data. Except at a few depths with higher concentrations (20–50%) in volcanic glass and carbonate ooze, gas hydrate occupies about 10% of the pore space in silty-clay sediments with sand and volcanic ash. [ABSTRACT FROM AUTHOR]

Simple Summary: Sesame (Sesamum indicum L.) is an important oilseed crop that is well known for its highly nutritious oil content. Due to its high oil content and nutritional properties, sesame is also known as the 'queen of oilseeds'. Phytoplasma-associated diseases such as phyllody and little leaf are critical threats to sesame cultivation worldwide. Sesame phyllody is the leading biotic constraint drastically affecting sesame productivity and resulting in yield losses of up to 80% in major sesame-producing countries in the world. In this study, we explored the role of DNA methylation in phytoplasma infection. Whole Genome Bisulfite Sequencing and a Quantitative analysis of DNA methylation using real-time PCR (qAMP) revealed an alteration of methylation pattern upon phytoplasma infection. Few selected development and defense-related loci were either hypo- or hypermethylated. We hereby report the first methylome study in healthy and phytoplasma-infected sesame. Our study provides fundamental insights into the role of DNA methylation in the symptom development of phytoplasma infection in sesame plants. Phytoplasma-associated diseases such as phyllody and little leaf are critical threats to sesame cultivation worldwide. The mechanism of the dramatic conversion of flowers to leafy structures leading to yield losses and the drastic reduction in leaf size due to Phytoplasma infection remains yet to be identified. Cytosine methylation profiles of healthy and infected sesame plants studied using Whole Genome Bisulfite Sequencing (WGBS) and Quantitative analysis of DNA methylation with the real-time PCR (qAMP) technique revealed altered DNA methylation patterns upon infection. Phyllody was associated with global cytosine hypomethylation, though predominantly in the CHH (where H = A, T or C) context. Interestingly, comparable cytosine methylation levels were observed between healthy and little leaf-affected plant samples in CG, CHG and CHH contexts. Among the different genomic fractions, the highest number of differentially methylated Cytosines was found in the intergenic regions, followed by promoter, exonic and intronic regions in decreasing order. Further, most of the differentially methylated genes were hypomethylated and were mainly associated with development and defense-related processes. Loci for STOREKEEPER protein-like, a DNA-binding protein and PP2-B15, an F-Box protein, responsible for plugging sieve plates to maintain turgor pressure within the sieve tubes were found to be hypomethylated by WGBS, which was confirmed by methylation-dependent restriction digestion and qPCR. Likewise, serine/threonine-protein phosphatase-7 homolog, a positive regulator of cryptochrome signaling involved in hypocotyl and cotyledon growth and probable O-methyltransferase 3 locus were determined to be hypermethylated. Phytoplasma infection-associated global differential methylation as well as the defense and development-related loci reported here for the first time significantly elucidate the mechanism of phytoplasma-associated disease development. [ABSTRACT FROM AUTHOR]

We present Monte Carlo (MC) simulation studies of phase separation in binary (AB) mixtures with bond-disorder that is introduced in two different ways: (i) at randomly selected lattice sites and (ii) at regularly selected sites. The Ising model with spin exchange (Kawasaki) dynamics represents the segregation kinetics in conserved binary mixtures. We find that the dynamical scaling changes significantly by varying the number of disordered sites in the case where bond-disorder is introduced at the randomly selected sites. On the other hand, when we introduce the bond-disorder in a regular fashion, the system follows the dynamical scaling for the modest number of disordered sites. For a higher number of disordered sites, the evolution morphology illustrates a lamellar pattern formation. Our MC results are consistent with the Lifshitz-Slyozov power-law growth in all the cases. [ABSTRACT FROM AUTHOR]

Background: Unhealthy alcohol use (UAU) is a leading cause of morbidity and mortality in the United States, contributing to 95,000 deaths annually. When offered in primary care, screening, brief intervention, referral to treatment (SBIRT), and medication-assisted treatment for alcohol use disorder (MAUD) can effectively address UAU. However, these interventions are not yet routine in primary care clinics. Therefore, our study evaluates tailored implementation support to increase SBIRT and MAUD in primary care. Methods: ANTECEDENT is a pragmatic implementation study designed to support 150 primary care clinics in Oregon adopting and optimizing SBIRT and MAUD workflows to address UAU. The study is a partnership between the Oregon Health Authority Transformation Center—state leaders in Medicaid health system transformation—SBIRT Oregon and the Oregon Rural Practice-based Research Network. We recruited clinics providing primary care in Oregon and prioritized reaching clinics that were small to medium in size (<10 providers). All participating clinics receive foundational support (i.e., a baseline assessment, exit assessment, and access to the online SBIRT Oregon materials) and may opt to receive tailored implementation support delivered by a practice facilitator over 12 months. Tailored implementation support is designed to address identified needs and may include health information technology support, peer-to-peer learning, workflow mapping, or expert consultation via academic detailing. The study aims are to 1) engage, recruit, and conduct needs assessments with 150 primary care clinics and their regional Medicaid health plans called Coordinated Care Organizations within the state of Oregon, 2) implement and evaluate the impact of foundational and supplemental implementation support on clinic change in SBIRT and MAUD, and 3) describe how practice facilitators tailor implementation support based on context and personal expertise. Our convergent parallel mixed-methods analysis uses RE-AIM (reach, effectiveness, adoption, implementation, maintenance). It is informed by a hybrid of the i-PARIHS (integrated Promoting Action on Research Implementation in Health Services) and the Dynamic Sustainability Framework. Discussion: This study will explore how primary care clinics implement SBIRT and MAUD in routine practice and how practice facilitators vary implementation support across diverse clinic settings. Findings will inform how to effectively align implementation support to context, advance our understanding of practice facilitator skill development over time, and ultimately improve detection and treatment of UAU across diverse primary care clinics. [ABSTRACT FROM AUTHOR]

Previously, we assessed that hypertension increases cataractogenesis. In the present study, we evaluated the effect of oral and topical administration of enalapril on two kidney one clip (2K1C)-induced hypertensive cataract model by evaluating the biochemical alteration of lenticular antioxidants, ionic content, ATPase activity, protein content and careful examination of the lenticular opacity. Animals were divided into normal and hypertensive animals. Hypertensive animals were divided into hypertensive control group (0.3% CMC), enalapril (oral) treatment group (20 mg/kg/day; p.o), and enalapril (topical) treatment group (0.1% w/v on the eye cornea) for a period of twelve weeks. During experimental study blood pressure, heart rate and morphology of the eyes were monitored biweekly. After twelve weeks, lenses were photographed and various catractogenic biochemical parameters were assessed. Enalapril (oral) treatment conserved the blood pressure (systolic and diastolic), restored the level of antioxidants, restored the lipid peroxidation marker, nitrite content, ionic content, ATPase function, protein content, and thus delayed the cataract formation. While, enalapril (topical) treatment exhibited anti-cataract effect without affecting the systolic and diastolic blood pressure that could be by restoring the antioxidant level, maintaining the ionic balance, balancing the protein levels, and by inhibiting the upregulated ocular renin angiotensin system. The overall results suggest that enalapril (topical) treatment showed conspicuous effect than enalapril (oral) treatment in adjourning the cataract formation. Based on the results, it may be concluded that upregulated ocular RAS by increasing oxidative stress and by misbalancing the lenticular ionic and protein content may lead to cataract formation in hypertensive condition. [ABSTRACT FROM AUTHOR]

Introduction: Cyclin D1 is a protein encoded by the CCND1 (BCL-1) gene on chromosome 11q13 and it is an important regulator of G1 to S phase progression. Over expression of cyclin D1 protein releases cells from their normal controls when they need to exit from the cell cycle. This obstructs their maturation, and promotes transformation into a malignant phenotype. Aim: To study the role of cyclin D1 expression in trephine biopsies of multiple myeloma patients and its association with C-Reactive Protein (CRP), β2-microglobulin level and treatment response rate. Materials and Methods: This prospective observational study was conducted at Department of Pathology in collaboration with Department of Clinical Haematology, King George's Medical University, Lucknow, India, from September 2018 to August 2019. Total 40 cases of multiple myeloma fulfilling inclusion and exclusion criteria were enrolled. Bone marrow aspiration and biopsy was done in all the cases. Immunohistochemical (IHC) expression of cyclin D1 on trephine biopsy was associated with CRP levels and β2-microglobulin expression. All investigations were repeated at six months follow-up and response was compared with expression of cyclin D1. The statistical tests applied were Chi-square test, Student t-test and paired t-test. Results: The age of cases ranged between 44 to 78 years and the mean age of the study subjects was 64.40±7.13 years. Total 67.5% of patients were males. On IHC, cyclin D1 expression was not observed in majority of cases (n=23), weak cyclin D1 expression was observed in 8 cases, while strong cyclin D1 expression was observed in 9 cases. Out of eight cases with weak cyclin D1 expression, five cases achieved partial response and two cases achieved complete response. One case was lost to follow-up. Among nine patients with strong cyclin D1 expression, six patients expired on six months follow-up and three patients achieved partial response. On comparison of two groups cyclin D1 positive and cyclin D1 negative cases it was found that cyclin D1 positive cases had an early age of onset, more than 50% plasma cells on marrow aspirate and were associated with plasmablastic morphology. Cyclin D1 positive cases also had increased CRP level as compared to cyclin D1 negative cases. Similarly, serum calcium, serum creatinine and β2-microglobulin levels were more in cyclin D1 positive group. Conclusion: Cases who have strong cyclin D1 expression at time of diagnosis showed poor response to treatment. This was also associated with increased serum CRP and β2-microglobulin levels. Hence, cyclin D1 can be used as a prognostic marker in multiple myeloma. [ABSTRACT FROM AUTHOR]

Introduction: Gestational diabetes mellitus (GDM) is a public health problem that currently affects a large part of the female population and has short‐ and long‐term consequences for the fetus and the mother. It has been reported that GDM affects 1%–14% of all pregnancies, and that its incidence has been steadily rising. In recent years while exploring the etiological factors responsible for the emergence of insulin resistance particularly that of transient nature, vitamin D has emerged as one of the possible factors. Although systematic review and metaanalysis of observational studies show that low blood vitamin D level during pregnancy is associated with 1.8 times higher odds of GDM as compared to those having normal blood vitamin D levels; however, individual observational studies about maternal vitamin D status and risk of GDM are conflicting, The aim of this study is to compare the levels of 25(OH) vitamin D in women with gestational diabetes mellitus and normoglycemic pregnant women to assess the pathogenic role of vitamin D in the causation of GDM. Materials and Methods: This study was conducted in the Department of Obstetrics and Gynecology, Era's Lucknow Medical College and Hospital (ELMCH), Lucknow from December 2018 to November 2020 The present study was an analytical case–control study, in which a total of 30 pregnant women in 24–28 weeks of gestation diagnosed as GDM using Diabetes in Pregnancy Study Group criteria were enrolled as cases while another 30 pregnant women in same gestational age range with normoglycemic profile were enrolled as controls. The 25(OH)D levels were assessed by the chemiluminecence immunoassay. The statistical analysis was performed using SPSS (Statistical Package for Social Sciences) Version 21.0. Results: On multivariate analysis, vegetarian diet and GDM were found to be significantly associated with vitamin D deficiency. The present study endorsed the relationship between vitamin D deficiency and GDM and showed a high prevalence of vitamin D deficiency, and that too at severe level could result in GDM. Appropriate awareness and intervention strategies are warranted on a larger sample. [ABSTRACT FROM AUTHOR]

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of pathological cerebrospinal fluid (CSF) accumulation and, therefore, treated largely by neurosurgical CSF diversion. The persistence of ventriculomegaly and poor neurodevelopmental outcomes in some post-surgical patients highlights our limited knowledge of disease mechanisms. Recent whole-exome sequencing (WES) studies have shown that rare, damaging de novo and inherited mutations with large effect contribute to ~ 25% of sporadic CH. Interestingly, multiple CH genes are key regulators of neural stem cell growth and differentiation and converge in human transcriptional networks and cell types pertinent to fetal neurogliogenesis. These data implicate genetic disruption of early brain development as the primary pathomechanism in a substantial minority of patients with sporadic CH, shedding new light on human brain development and the pathogenesis of hydrocephalus. These data further suggest WES as a clinical tool with potential to re-classify CH according to a molecular nomenclature of increased precision and utility for genetic counseling, outcome prognostication, and treatment stratification. [ABSTRACT FROM AUTHOR]

Background: Decision to delivery [DDI] interval is the time interval between decision for caesarean section [CS] and delivery of baby. The ideal DDI for emergency CS is not known; there is controversy over the best DDI to avoid preventable perinatal morbidity and mortality. Aims and Objectives: This study was conducted to find out the DDI we could achieve for Category-1 and Category-2 CS and evaluate our findings against the recommendations by National Institute for Clinical Excellence [NICE]. We also studied the association of DDI with perinatal outcome and explored the reasons for prolongation of DDI. Materials and Methods: This was a prospective study conducted over a period of 6 months. All women who underwent CS and meeting the inclusion criteria were recruited for the study. DDI was calculated as the time interval between decision making and delivery of baby, in minutes [min]. Data was collected for maternal socio-demographic variables, CS indication and complications and perinatal outcome. Analysis was done using SPSS version 21.0. Results: Ninety out of one hundred eighty-one CS was evaluated. Cases were grouped as Group I [including cases where we could achieve the recommended DDI] and Group II [including cases where we could not achieve the recommended DDI]. The average DDI was 55.04 min for category-1 and 55.13 for category-2 CS. For Category-1 CS, all the cases qualified for entry into Group II because we could not achieve a DDI of 30 min. For Category-2 CS there were 22 cases in Group I and 14 cases in Group II. There was no difference in perinatal outcome between the groups. Conclusion: It was not feasible to achieve the 30 min DDI for Category-1 CS in the present study. The DDI of 30-75 min for Category-2 could be achieved in 61.11% cases. The most common reason for failure to achieve the recommended DDI was related to issues with anaesthesia in the pre-operative room as well as inside the theatre in the pre-induction phase. Delay in category-2 CS was not associated with poor perinatal outcome. [ABSTRACT FROM AUTHOR]

The Himalayan region is characterised by snow-covered mountains and glacierised basins which directly or indirectly regulates many large to small rivers downstream. To simulate and forecast stream-flow in these glacierised basins, an accurate snow cover area (SCA) estimation is of utmost importance. The present study assesses the snow cover dynamics (monthly, annual and seasonal) in the Changme Khangpu Basin (CKB) for almost two decades, from 2002 to 2019. The spatial and temporal variations in the SCA have been estimated using Moderate Resolution Imaging Spectro-radiometer (MODIS) 8-day maximum composite snow cover products from Terra (MOD10A2). Further, the SCA change has been compared with a remotely sensed meteorological parameter like temperature. The result shows a decreasing trend in annual mean SCA of the basin in the last two decades and an increase in seasonal mean SCA in the ablation period (May, June, July, August and September), whereas a decrease in seasonal mean SCA in accumulation period has been observed. The seasonal change in SCA will help in estimating the availability of water in the region for the people residing downward in the valley. [ABSTRACT FROM AUTHOR]

2-(((5-mercapto-1,3,4-thiadiazol-2-yl)imino)methyl)phenol (MTP) was synthesized, self-assembled on the surface of gold (Au) electrode (Au-MTP) followed by characterization using Cyclic voltammetry (CV) and Electrochemical impedance spectroscopy (EIS). CV and EIS confirmed the formation of well-organized Au-MTP SAM free from defects and pinholes. Au-MTP was further utilized as a platform for sensing of Hg2+ using EIS. The results showed sensitive and selective response of Au-MTP towards Hg2+ in the linear concentration range from 1.0 × 10−10 M to 1.0 × 10−4 M with limit of detection (LoD) of 5.6 × 10−11 M. Furthermore, MTP was self-assembled on gold nanoparticles (AuNPs) and MTP bound gold nanoparticles (MTP-AuNPs) so obtained were used as modifier for construction of carbon paste electrode (CPE). Hg2+-CPE exhibited Nernstian response towards Hg2+ with slope of 28.3 mV/decade in the concentration range from 1.0 × 10−5 M to 1.0 × 10−1 M with LoD of 6.3 × 10−6 M. Both the Au-MTP EIS sensor and Hg2+-CPE were successfully applied for estimation of Hg2+ content in tap water samples. [Display omitted] • A chelating Schiff base thiol (MTP) was synthesized and characterized. • Au-MTP SAM was characterized using CV and EIS. • Au-MTP showed EIS response towards Hg2+ with LoD 5.6 × 10−11 M. • Hg2+-CPE showed Nernstian response of 28.3 mV/decade with LoD 6.3 × 10−6 M. • Both EIS sensor and CPE were applied for determination of Hg2+ in tap water. [ABSTRACT FROM AUTHOR]

Despite sharing conserved substrate-binding residues, members of 3-hydroxyisobutyrate dehydrogenase (HIBADH) superfamily show remarkable differences in substrate preference. Cysteine residues were identified within a radius of 6 Å surrounding both the active site and the substrate entry site of HIBADH enzyme from Mycobacterium tuberculosis (MtHIBADH). Chemical modification with thiol-modifying reagents, pCMB and DTNB, abrogated the dehydrogenase activity of the enzyme. The loss in activity followed pseudofirst-order kinetics as a function of the concentration of pCMB. S-HIBA (substrate) binding provided partial protection, while NAD (cofactor) binding provided ~70% protection from thiol-modifying reagent. Site-directed mutagenesis of cysteine residues present in the MtHIBADH enzyme identified the indispensable role of Cys-210 residue, located at C-terminal domain, for its dehydrogenase activity. Cys-210 mutation to serine reduced the dehydrogenase activity by ~2-fold while mutation to alanine strikingly reduced the activity by ~140-fold. C210A mutation did not perturb the state of oligomerization of the enzyme but perturbed the secondary structure content. Structural analysis revealed the involvement of Cys-210 residue in inter-chain interaction with Gln178, which acts as hydrogen bond donor and coordinates with Cys-210 and Gly-208 of the adjacent subunit. The data demonstrate a critical role of Cys210 residue in maintaining the conformation and rigidity of loop composed of substrate-interacting residues involved in the entry of S-HIBA substrate in MtHIBADH. [ABSTRACT FROM AUTHOR]

Detailed investigation on "1-x-yBNT-xBKT-yKNN" was done for better understanding of its phase diagram which is crucial for estimating a useful composition range for actuation applications. A phase diagram is proposed along with a MPB between "rhombohedral ferroelectric and tetragonal ferroelectric" phases in the range x = 0.05 (0.04 ≤ y < 0.08) and x = 0.10 (0.02 ≤ y < 0.06). However addition of KNN above the critical value y ≥ 0.12 is observed to drive the system toward cubic structure. A region having large "electric field induced strain (EFIS)" value (∼0.45%) is also identified in the phase diagram. [ABSTRACT FROM AUTHOR]

Detailed investigation on "1-x-yBNT-xBKT-yKNN" was done for better understanding of its phase diagram which is crucial for estimating a useful composition range for actuation applications. A phase diagram is proposed along with a MPB between "rhombohedral ferroelectric and tetragonal ferroelectric" phases in the range x = 0.05 (0.04 ≤ y < 0.08) and x = 0.10 (0.02 ≤ y < 0.06). However addition of KNN above the critical value y ≥ 0.12 is observed to drive the system toward cubic structure. A region having large "electric field induced strain (EFIS)" value (∼0.45%) is also identified in the phase diagram. [ABSTRACT FROM AUTHOR]

In this work, magnetoelectric properties of a co-sintered bilayered composite of non-lead based piezoelectric 0.97(Bi0.5Na0.5TiO3)-0.03(K0.47Na0.47Li0.06Nb0.74Sb0.06Ta0.2O3) and magnetostrictive Co0.6Zn0.4Fe1.7Mn0.3O4 are presented. Similar optimal sintering conditions of the individual components lead to a very clean interface as evidenced in the scanning electron microscopy, angle dispersive X-ray diffraction, and energy-dispersive X-ray (EDX) results. Clean interface results in strong intimate mechanical coupling between both components and causes a maximum transfer of induced strain, leading to a large magnetoelectric coupling ~142 mV/cm.Oe measured in longitudinally magnetized-transversely polarized configuration (L-T mode). Remnant polarization ~32 μC/cm2, remnant magnetization ~0.50 emu/g, and sufficiently high self biased magnetoelectricity ~135 mV/cm Oe (L-T mode) were observed for this composite. [ABSTRACT FROM AUTHOR]

Detailed study of ac conductivity of "1-x-y (Bi0.5Na0.5)TiO3–x(Bi0.5K0.5TiO3)–y(Na0.5K0.5)NbO3 (BNT-BKT-KNN)" with x = 0.2 y = 0.01 for 25 °C ≤ T ≤ 350 °C and 40 Hz≤f ≤ 100kHz is presented. Below depolarization temperature (Td ∼ 80 °C), a temperature independent translational short range hopping conduction of bipolarons between Ti+3 and Ti+4 sites was observed. Above Td, σac, α and n were found to be both frequency and temperature dependent. Thermally activated hopping assisted by large polarons was seen in the frequency range 40 Hz≤f ≤ 10kHz; whereas, reorientational hopping of charge carriers (hopping between two charge defects) assisted by small polaron mechanism was evident in the high frequency region (10 kHz

High glucose level is a strong initiator of both oxidative stress and DNA damage to various cellular proteins. This activates the poly ADP-ribose polymerase (PARP) enzyme, which is responsible for disturbing physiological energy metabolic homeostasis. The present study aimed to elucidate the association between stress and the PARP pathway by using resveratrol (RSV) and nicotinamide (NAM, PARP inhibitor) to treat diabetic cataract. Albino rats were used for the experimental study. A single streptozotocin administration (55 mg/kg, i.p.) prompted diabetes in the animals. The experimental groups were the normal group (non-diabetic) and the diabetic groups: the diabetic control animals (group D), the diabetic animals treated with RSV at 40 mg/kg/day, i.p. (D+ RSV group), NAM at 100 and 300 mg/kg/day, i.p. (D+ NAM100, D+ NAM300 groups, respectively), and a combination of RSV and NAM i.p. (D+ RSV+NAM100 = Combi 1 group, D+ RSV+NAM300 = Combi 2 group). Glucose levels and the eyes were examined biweekly; various cataractogenic parameters in the lenses were examined after completion of the eight-week experimental protocol. Compared to diabetic control, RSV monotherapy significantly decreased hyperglycemia and other lenticular alterations. NAM at the high dose only showed beneficial effects without altering the blood glucose level, lenticular aldose reductase (AR) activity, and sorbitol content, primarily restored the lenticular NAD level and decreased oxidative stress in diabetic rats. These findings regarding NAM treatment indicate that a pathway other than the antioxidant defense system and the polyol pathway, which might be due to PARP inhibition, is involved in diabetic cataracts. Moreover, compared to RSV monotherapy, combination treatments were effective. These results indicate that hyperglycemia and oxidative-osmotic-nitrosative stress play central roles in the pathophysiology of diabetic cataracts. Moreover, our study also revealed that concurrent treatment with the RSV and NAM may prove useful in the pharmacotherapy of diabetes and its secondary complications such as cataract. [ABSTRACT FROM AUTHOR]

Liver abscess in pregnancy is a rare entity and can be a life threatening condition. Here we present A case of amoebic liver abscess in 25 years old lady in third trimester of pregnancy, with highlights on treatment difficulties which we had faced in the management and timely intervention leads to good fetomaternal outcome. [ABSTRACT FROM AUTHOR]

N-Linked glycans are critical to the infection cycle of HIV, and most neutralizing antibodies target the high-mannose glycans found on the surface envelope glycoprotein-120 (gp120). Carbohydrate-binding proteins, particularly mannose-binding lectins, have also been shown to bind these glycans. Despite their therapeutic potency, their ability to cause lymphocyte proliferation limits their application. In this study, we report one such lectin named horcolin (Hordeum vulgare lectin), seen to lack mitogenicity owing to the divergence in the residues at its carbohydrate-binding sites, which makes it a promising candidate for exploration as an anti-HIV agent. Extensive isothermal titration calorimetry experiments reveal that the lectin was sensitive to the length and branching of mannooligosaccharides and thereby the total valency. Modeling and simulation studies demonstrate two distinct modes of binding, a monovalent binding to shorter saccharides and a bivalent mode for higher glycans, involving simultaneous interactions of multiple glycan arms with the primary carbohydrate-binding sites. This multivalent mode of binding was further strengthened by interactions of core mannosyl residues with a secondary conserved site on the protein, leading to an exponential increase in affinity. Finally, we confirmed the interaction of horcolin with recombinant gp120 and gp140 with high affinity and inhibition of HIV infection at nanomolar concentrations without mitogenicity [ABSTRACT FROM AUTHOR]

To find out the levels of IL-8 in patients of chronic pelvic pain & infertility & assess its role in predicting endometriosis. It was a prospective study conducted over 50 patients of chronic pelvic pain & infertility undergoing diagnostic laparoscopy. During this procedure peritoneal fluid &blood samples were collected & prepared for ELISA, IL-8 estimation. Serum IL-8 levels of >22.16 pg/ml& peritoneal fluid level of >7.98 pg/ml were found to be 100% sensitive & specific. Thus they can be taken as cut-off value for predicting endometriosis. IL-8 was significantly elevated in the serum & peritoneal fluid in the patients of endometriosis diagnosed by diagnostic laparoscopy. Our study indicates that serum & peritoneal fluid IL-8 levels can discriminate patients with& without endometriosis and could serve as one of the non-invasive ideal markers to cut short the delay in the diagnosis & management of infertility and also lays down a foundation for further research in correlating IL -8 levels with disease severity. [ABSTRACT FROM AUTHOR]

We use the unsupervised and supervised neural network methods together to predict lithology of a gas hydrate reservoir from downhole data in the Krishna–Godavari (KG) offshore basin, India. In this study, we successfully identify the host litho-units of gas hydrate and show its effects in the identification of lithology using neural network techniques, which is not reported earlier. We use well log data acquired at three holes (10A, 03A and 04A) in 2006 during the first expedition of the Indian National Gas Hydrate Program (NGHP-01). Five different logging while drilling data (e.g. density, neutron porosity, gamma ray, resistivity and sonic) are considered for the mapping of lithology and gas hydrate. In the presence of gas hydrate, the resistivity and sonic velocity of the host sediments increase significantly, whereas density, neutron porosity and gamma ray are negligibly affected. Therefore, we calculate resistivity and sonic velocity for water-saturated sediment (without gas hydrate) theoretically to remove the effects of gas hydrate. At first, we apply the seven unsupervised classification methods (i.e. elbow, dendrogram, K -means, 3-D clustering, principal component analysis, Devies–Bouldin index and self-organizing map) to the data with gas hydrate (e.g. observed) and without gas hydrate (i.e. water-saturated/theoretical) to assess the data dimensionality and the number of clusters/litho-units. Each of the unsupervised schemes has its own pros and cons, and may provide different number of cluster/litho-units; sometimes, it is difficult to interpret from only one method. However, all seven methods provide same number of clusters in our study. Then, we apply the supervised classification method (i.e. Bayesian neural networks optimized by hybrid Monte Carlo searching technique) to the training data to refine the defined litho-units and map them with depth. Our approach identifies four types of litho-units and illustrates that the lithology in this area is dominated by clay (∼64 per cent) with some amount of silty clay, silt and minor sand. Gas hydrate is found in clay, silty clay and silt and not in sand. Results also show that, if gas hydrate is not considered as a separate unit, it is distributed as lithology in its hosts (i.e. clay, silty clay and silt). The method is very stable up to ∼15 per cent of random noise added to the data and results are well matched with the analysis of recovered core data. Identified lithologies at three wells correlate very well with seismic section crossing the wells. Very low permeability (<0.1 mD) estimated at three wells also indicates the clay-dominated lithology in our study area. [ABSTRACT FROM AUTHOR]

Results on two series of lead-free piezoelectric solid solutions of 1-x-y(Bi0.5Na0.5)TiO3-x(Bi0.5K0.5TiO3)-y(Na0.5K0.5)NbO3 (BNT-BKT-KNN) ceramics, synthesized in the vicinity of ferroelectric rhombohedral (x=0.17) and ferroelectric tetragonal (x=0.20) phase boundary of 1-x(BNT)-xBKT are presented. Orthorhombic KNN in stoichiometric proportion as third component with 0.0≤y≤0.06 is added to prepare these two series (i) with x=0.17 and (ii) with x=0.20. Addition of KNN up to a critical y is observed to improve tetragonality in both series and solid solubility of KNN was verified at least up to y=0.1 in this system. Depolarization temperature Td of these stoichiometric BNT-BKT-KNN series were found to be considerably lower than that of their parent BNT-BKT compositions. As a result of this, coexistence of polar and nonpolar phases for compositions at morphotropic phase boundary (MPB) were indicated at room temperature, resulting in pinched polarization versus electric field (P-E) loops and large strain (strain of ∼0.80% was observed for y=0.01 sample in ×20 series and strain of 0.50% was seen for y=0.04 sample in ×17 series) The MPB of ×17 and ×20 series found to be at y=0.04 and y=0.01, respectively. [ABSTRACT FROM AUTHOR]

Mediator, a multiprotein complex, is an important component of the transcription machinery. In plants, the latest studies have established that it functions as a signal processor that conveys transcriptional signals from transcription factors to RNA polymerase II. Mediator has been found to be involved in different developmental and stress-adaptation conditions, ranging from embryo, root, and shoot development to flowering and senescence, and also in responses to different biotic and abiotic stresses. In the last decade, significant progress has been made in understanding the role of Mediator subunits in root development. They have been shown to transcriptionally regulate development of almost all the components of the root system architecture—primary root, lateral roots, and root hairs. They also have a role in nutrient acquisition by the root. In this review, we discuss all the known functions of Mediator subunits during root development. We also highlight the role of Mediator as a nodal point for processing different hormone signals that regulate root morphogenesis and growth. [ABSTRACT FROM AUTHOR]

Alveolar rhabdomyosarcoma in a rare aggressive tumour which manifests in children and young adults. The site of alveolar rhabdomyosarcoma in vagina is also extremely rare. We presented a case report of 38 yrs.lady who was having complain of intermenstrual bleeding & discharge per vaginum from last 6 months. A large fleshy infiltrative bluish friable mass (3*3cm) present at the junction of middle and upper 1/3rd and upper 1/3rd of posterior vaginal wall. Another similar mass (2* 2cm) was also present in the lateral vaginal wall. Wide excision of both growth was done & postoperatively chemotherapy was given. [ABSTRACT FROM AUTHOR]

Phytoplasma, an emerging plant pathogen is an endocellular obligate parasite of plant phloem tissues with highly reduced genomes and low GC content. They contain a minimal set of genes essential for survival as an intracellular parasite. The role of G-Quadruplexes in pathogenicity has been reported in a variety of microbial pathogens. Detailed investigation on the genome wide occurrence and distribution of Putative G-Quadruplex forming Sequences (PGQSs) in the AT-rich genome of Onion yellows phytoplasma (strain OY-M) was carried out. Relative enrichment and depletion of these putative secondary structures in different genomic regions of OY-M was investigated with an aim to unravel their association with functionally important genomic locations. PGQSs density of 0.4407/Kbp was detected in the genome of OY-M phytoplasma, which is significantly higher than the average PGQSs density (0.136/Kbp) reported for other members of its phylum, namely Tenericutes. A non-random distribution of PGQSs across the length of the genome was observed. Putative promoter regions of OY-M were found to be particularly enriched in PGQSs followed by genic regions. The repeat rich regions were identified to have minimum PGQSs density. Presence of PGQSs in important genes such as those involved in secretory pathways of virulent factors, transport related functions, rRNA and tRNA was particularly intriguing. Our study reports for the first time a detailed investigation on the genome-wide locations of putative G-Quadruplexes in phytoplasma and highlights the need to further investigate their role in the metabolism and also in the mechanism of pathogenicity. [ABSTRACT FROM AUTHOR]

Objectives: Direct oral anticoagulants (DOACs) are now replacing vitamin K oral anticoagulants (VKAs) owing to superior efficacy, rapid action, less bleeding, wider therapeutic range,and fewer food and drug interactions.Unfortunately, the available data on the use of DOACs, particularly dabigatran, for treatment of left ventricular thrombus (LVT) issparse.We have hereby presented the largest study on use of dabigatran in LVT. Methods: Retrospective data of patients having LVT as diagnosed by transthoracic echocardiography (TTE) was screened. Patients on dabigatran were included in the study and follow up data of 6 months was obtained through medical records. Results: f the 15 patients included in the study, the most frequent etiology was ischemic heart disease (67%), including 7 patients of STEMI (47%), followed by non-ischemic cardiomyopathy in 5 patients (33%). Only one patient, with STEMI, developed mild gastrointestinal bleeding at 3 months. Complete clot resolution was seen in 2 patients (13%) at first week of follow up and total 5 patients (33%) at the end of second week. The rate of clot resolution at 1 month, 3 months, and 6 months were 80%, 93% and 100%, respectively. The median duration required for complete clot resolution was 30 days (IQR=14-30). Conclusion: Dabigatran appears to be safe, highly efficacious and results in rapid LV clot resolution. DOACs may be a suitable alternative to warfarin in treatment of LV thrombus. However, larger studies are required to validate this hypothesis. [ABSTRACT FROM AUTHOR]

Simulation of inductors has been a very popular area of analog circuit research and the alternative choice for realizing inductor-based circuits in integrated circuits. In this paper, lossless, grounded and floating inductor topologies using current-controlled-current-feedback amplifier (CC-CFA) with single grounded capacitor are presented. The proposed topologies can be tuned electronically by changing the biasing current of the CC-CFA. Two topologies for grounded inductor simulator employ two CC-CFA and one grounded capacitor. One topology for floating inductor simulator employs three CC-CFA and one grounded capacitor. The performance of the grounded and floating inductor simulators are demonstrated on resonant circuits. The theoretical analysis is verified by PSPICE simulation results. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has greatly advanced in recent years. Most immunotherapeutic strategies are based on the use of immune checkpoint blockade to unleash antitumor immune responses or on the induction or adoptive transfer of immune effector cells. We aim to develop therapeutic vaccines based on recombinant Semliki Forest virus vectors to induce tumor-specific effector immune cells. In this review, we describe our ongoing work on SFV-based vaccines targeted against human papillomavirus- and hepatitis C virus-related infections and malignancies, focusing on design, delivery, combination strategies, preclinical efficacy and product development for a first-in-man clinical trial with an HPV-specific vaccine. [ABSTRACT FROM AUTHOR]

Abstract The αvβ3 integrin has been shown to promote aggressive phenotypes in many types of cancers, including prostate cancer. We show that GFP-labeled αvβ3 derived from cancer cells circulates in the blood and is detected in distant lesions in NOD scid gamma (NSG) mice. We, therefore, hypothesized that αvβ3 travels through exosomes and tested its levels in pools of vesicles, which we designate extracellular vesicles highly enriched in exosomes (ExVs), and in exosomes isolated from the plasma of prostate cancer patients. Here, we show that the αvβ3 integrin is found in patient blood exosomes purified by sucrose or iodixanol density gradients. In addition, we provide evidence that the αvβ3 integrin is transferred through ExVs isolated from prostate cancer patient plasma to β3-negative recipient cells. We also demonstrate the intracellular localization of β3-GFP transferred via cancer cell-derived ExVs. We show that the ExVs present in plasma from prostate cancer patients contain higher levels of αvβ3 and CD9 as compared to plasma ExVs from age-matched subjects who are not affected by cancer. Furthermore, using PSMA antibody-bead mediated immunocapture, we show that the αvβ3 integrin is expressed in a subset of exosomes characterized by PSMA, CD9, CD63, and an epithelial-specific marker, Trop-2. Finally, we present evidence that the levels of αvβ3, CD63, and CD9 remain unaltered in ExVs isolated from the blood of prostate cancer patients treated with enzalutamide. Our results suggest that detecting exosomal αvβ3 integrin in prostate cancer patients could be a clinically useful and non-invasive biomarker to follow prostate cancer progression. Moreover, the ability of αvβ3 integrin to be transferred from ExVs to recipient cells provides a strong rationale for further investigating the role of αvβ3 integrin in the pathogenesis of prostate cancer and as a potential therapeutic target. Highlights • First study to show αvβ3 integrin in exosomes isolated from prostate cancer patient blood. • First study to isolate PSMA-positive exosomes from prostate cancer patient blood using iodixanol density gradients. • αvβ3 integrin is expressed in a subset of exosomes characterized by PSMA, CD9, CD63, and an epithelial marker, Trop-2. • αvβ3 integrin is transferred to recipient cells through extracellular vesicles isolated from prostate cancer patient blood. [ABSTRACT FROM AUTHOR]

Background: Renal involvement in HIV patients is relatively common and quite broad. However, despite an increasingly large number of HIV patients in Asia, systematic studies of renal involvement are lacking. Objectives: The study was carried out to delineate the clinical spectrum of renal disease in HIV/AIDS patients hospitalised in a tertiary care centre. Patients and Methods: A total of 510 consecutive hospitalised HIV/AIDS with age >18years were included in the study. Detailed demographic, clinical and laboratory data including urinalysis was obtained from all participants. Results: Electrolyte disorders were seen in 71% of patients, with the most frequent being hyponatremia (61%). Acute renal failure was seen in 15.8% and CKD was found in 13% of HIV patients. Dipstick proteinuria of grade ≥1+ was seen in 147 patients (29% of total). CD4 count had a significant positive correlation with creatinine clearance, hyponatremia and total leukocyte count, and significant negative correlation with duration of disease and proteinuria. Conclusion: Electrolyte disorders and renal involvement are quite common in HIV/AIDS patients from India. Prompt diagnosis and management is required as their presence carry higher morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) has become epidemic in HIV/AIDS patients across Western and Eastern countries. HIV-associated nephropathy (HIVAN) has been consistently reported in studies from North America, Europe and African countries. However, studies from Asian countries are very sparse and differ strikingly in histological spectrum of renal disease, particularly in presence of HIVAN. Objectives: The study was carried out to in a teaching hospital from India to delineate the histological spectrum of renal disease and detect presence HIVAN in those with significant proteinuria (≥1gm/day). Patients and Methods: Urine analysis was done in 510 consecutive hospitalised HIV/AIDS patients after screening 640 such patients with age >18years. Patients with dipstick proteinuria ≥1+ were subjected to 24-hour urinary protein estimation. Renal biopsy was done in 10 patients with proteinuria ≥1gm/day. Results: Dipstick proteinuria ≥1+ was present in 29% patients. In patients undergoing kidney biopsy, the most frequent glomerular lesion was mesangial proliferative glomerulonephritis (30%) followed by HIVAN (20%). Tubulo-interstitial lesions were seen in 60% of biopsies. Pooled analysis of all the available kidney biopsy series from India revealed prevalence of HIVAN to be 16.5%. Conclusion: Contrary to the popular belief, HIVAN appears to be a common entity in this part of world too. High degree of clinical suspicion is required as diagnosis of HIVAN caries higher morbidity and mortality. Moreover, an early diagnosis and timely management can improve prognosis in such patients. [ABSTRACT FROM AUTHOR]

• Development of azo coupling based impedimetric sensors for TCS. • Electrochemical characterization of SAMs using CV and EIS. • Surface reactions were validated through UV-visible, FTIR, NMR and FESEM-EDX. • EIS sensors exhibited wide linear range, low LODs and excellent selectivity. • TCS content was successfully analysed in real samples. Extensive use of triclosan (TCS) in commercially available personal and health care products has led to its abundance in environment (water, soil), resulting in adverse impact on aquatic, marine, animal and human life. The present work is intended towards the development of simple and fast electrochemical sensors for trace level detection of TCS in aqueous media. The working of sensors is based on surface diazotization of self-assembled monolayers (SAMs) of two aminothiols, 4-aminothiophenol (4-ATP) and 5-amino-2-mercaptobenzimidazole (AMB) on polycrystalline gold electrodes. Using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), self-assembly of two aminothiols was confirmed as both offered significant impedance to [Fe(CN) 6 ]3-/4− redox probe. The exposed amino groups of two self-assembled aminothiols were subjected to diazotization and diazo derivatives so formed were utilized as platform for impedimetric sensing of TCS through azo coupling. The step-by-step study of self-assembly, diazotization and azo coupling was conducted using different techniques such as FTIR, UV-visible, NMR, FESEM and EDX. The proposed ATP and AMB based EIS sensors exhibited sensitivity towards TCS in wide linear concentration range of 1.0 × 10-10 M – 1.0 × 10-2 M and 1.0 × 10-12 M – 1.0 × 10-4 M with lower detection limits of 5.6 × 10-11 M and 7.9 × 10-13 M, respectively. A good selectivity was observed in the presence of common metal ions (Na+, K+, Ca2+, Mg2+, Cu2+, Fe3+, Zn2+, Co2+) and surfactants (SDS, Triton X-100, Triton X-114). Using proposed EIS sensors, the estimation of TCS in personal care products (soap, facewash, handwash) and water samples (surface and groundwater) has been successfully achieved. [Display omitted] [ABSTRACT FROM AUTHOR]

Liver abscess in pregnancy is a rare entity and can be a life threatening condition. Here we present A case of amoebic liver abscess in 25 years old lady in of pregnancy, with highlights on treatment third trimester difficulties which we had faced in the management and timely intervention leads to good fetomaternal outcome. [ABSTRACT FROM AUTHOR]

Many lakes around the world exhibit acute environmental stress due to water transfers, persistent droughts, and polluted runoff. In addition, falling water levels worsen air quality by exposing desiccated shores. To our knowledge, however, no published hedonic study has analyzed the costs of deteriorating water quality jointly with the air quality impacts of falling water levels for a large inland water body. We conduct such an analysis for the Salton Sea, the largest lake in California. Our spatial autoregressive models estimated on single-family properties located within 10 miles (16.1 km) of the Sea show that a 1 km reduction in distance to the Sea results in a $595 decrease in the price of a single-family residence. In addition, a 1% increase in annual particulate matter concentration reduces the value of the average family residence by $1,140. These results highlight the vulnerability of poor rural communities to deteriorating environmental conditions. [ABSTRACT FROM AUTHOR]

Paper is a versatile, flexible, porous, and eco-friendly substrate that is utilized in the fabrication of low-cost devices and biosensors for rapid detection of analytes of interest. Paper-based sensors provide affordable platforms for simple, accurate, and rapid detection of diseases, in addition to monitoring food quality, environmental and sun exposure, and detection of pathogens. Paper-based devices provide an inexpensive technology for fabrication of simple and portable diagnostic systems that can be immensely useful in resource-limited settings, such as in developing countries or austere environments, where fully-equipped facilities and highly trained medical staff are absent. In this work, we present the different types of paper that are currently utilized in fabrication of paper-based sensors, and common fabrication techniques ranging from wax printing to origamiand kirigami-based approaches. In addition, we present different detection techniques that are employed in paper-based sensors such as colorimetric, electrochemical, and fluorescence detection, chemiluminescence, and electrochemiluminescence, as well as their applications including disease diagnostics, cell cultures, monitoring sun exposure, and analysis of environmental reagents including pollutants. Furthermore, main advantages and disadvantages of different types of paper and future trends for paper-based sensors are discussed. [ABSTRACT FROM AUTHOR]

Biochemical and crystallographic studies on Mycobacterium tuberculosis 3-hydroxyisobutyric acid dehydrogenase (MtHIBADH), a member of the 3-hydroxyacid dehydrogenase superfamily, have been carried out. Gel filtration and blue native PAGE of MtHIBADH show that the enzyme is a dimer. The enzyme preferentially uses NAD+ as the cofactor and is specific to S-hydroxyisobutyric acid (HIBA). It can also use R-HIBA, L-serine and 3-hydroxypropanoic acid (3-HP) as substrates, but with much less efficiency. The pH optimum for activity is ~11. Structures of the native enzyme, the holoenzyme, binary complexes with NAD+, S-HIBA, R-HIBA, L-serine and 3-HP and ternary complexes involving the substrates and NAD+ have been determined. None of the already known structures of HIBADH contain a substrate molecule at the binding site. The structures reported here provide for the first time, among other things, a clear indication of the location and interactions of the substrates at the active site. They also define the entrance of the substrates to the active site region. The structures provide information on the role of specific residues at the active site and the entrance. The results obtained from crystal structures are consistent with solution studies including mutational analysis. They lead to the proposal of a plausible mechanism of the action of the enzyme. [ABSTRACT FROM AUTHOR]

Administration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, data regarding the optimal timing of G-CSFs post-transplantation are limited and conflicting. This retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical Center between November 5, 2013, and August 9, 2016, of adult inpatient autologous PBSCT recipients who received G-CSF empirically starting on day +5 (early) versus on those who received G-CSF on day +12 only if absolute neutrophil count (ANC) was <0.5 × 10 9 /L (ANC-driven). G-CSF was dosed at 300 µg in patients weighing <75 kg and 480 µg in those weighing ≥75 kg. One hundred consecutive patients underwent autologous PBSCT using either the early (n = 50) or ANC-driven (n = 50) G-CSF regimen. Patient and transplantation characteristics were comparable in the 2 groups. In the ANC-driven group, 24% (n = 12) received G-CSF on day +12 and 60% (n = 30) started G-CSF earlier due to febrile neutropenia or at the physician's discretion, 6% (n = 3) started after day +12 at the physician's discretion, and 10% (n = 5) did not receive any G-CSF. The median start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in the early group ( P  < .0001). For the primary outcome, the median time to neutrophil engraftment was 12 days (interquartile range [IQR] 11-13 days) in the early group versus 13 days (IQR, 12-14 days) in the ANC-driven group ( P  = .07). There were no significant between-group differences in time to platelet engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group ( P  = .04); however, there was no significant between-group difference in the incidence of positive bacterial cultures or transfer to the intensive care unit. The duration of G-CSF administration until neutrophil engraftment was 6 days in the early group versus 3 days in the ANC-driven group ( P  < .0001). The median duration of post-transplantation hospitalization was 15 days (IQR, 14-19 days) in the early group versus 16 days (IQR, 15-22 days) in the ANC-driven group ( P  = .28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven initiation of G-CSF following autologous PBSCT were associated with a similar time to neutrophil engraftment, length of stay post-transplantation, and 1-year overall survival. [ABSTRACT FROM AUTHOR]

Background: Only a handful of long noncoding RNAs have been functionally characterized. They are known to modulate regulation through interacting with other biomolecules in the cell: DNA, RNA and protein. Though there have been detailed investigations on lncRNA-miRNA and lncRNA-protein interactions, the interaction of lncRNAs with DNA have not been studied extensively. In the present study, we explore whether lncRNAs could modulate genomic regulation by interacting with DNA through the formation of highly stable DNA:DNA:RNA triplexes.Methods: We computationally screened 23,898 lncRNA transcripts as annotated by GENCODE, across the human genome for potential triplex forming sequence stretches (PTS). The PTS frequencies were compared across 5'UTR, CDS, 3'UTR, introns, promoter and 1000 bases downstream of the transcription termination sites. These regions were annotated by mapping to experimental regulatory regions, classes of repeat regions and transcription factors. We validated few putative triplex mediated interactions where lncRNA-gene pair interaction is via pyrimidine triplex motif using biophysical methods.Results: We identified 20,04,034 PTS sites to be enriched in promoter and intronic regions across human genome. Additional analysis of the association of PTS with core promoter elements revealed a systematic paucity of PTS in all regulatory regions, except TF binding sites. A total of 25 transcription factors were found to be associated with PTS. Using an interaction network, we showed that a subset of the triplex forming lncRNAs, have a positive association with gene promoters. We also demonstrated an in vitro interaction of one lncRNA candidate with its predicted gene target promoter regions.Conclusions: Our analysis shows that PTS are enriched in gene promoter and largely associated with simple repeats. The current study suggests a major role of a subset of lncRNAs in mediating chromatin organization modulation through CTCF and NSRF proteins. [ABSTRACT FROM AUTHOR]

A prospective study was conducted in upgraded department of ophthalmology Government Medical College Jammu. The aim was to evaluate the surgically induced astigmatism (SIA) by 2.8 mm superior clear corneal incision after phacoemulsification. Fifty eyes of exact number of patients were included in the study. The average age and preoperative astigmatism was computed. All patients were treated with 2.8 mm clear corneal superior approach phacoemulsification. Patients received detailed ophthalmological investigations in addition to keratometry both pre- and post-operatively. SIA was calculated by using SIA Calculator Version 2.1. Age wise the cataract patients were in all four age groups of 41-50 years (15/ 30%), 51-60 years (14/ 28%), 61-70 years (18/ 36%) and 71-80 years (3/ 6%). The mean age of cataract patients was 56.8 ± 9.31 years. The preoperative astigmatism under study patients ranged from 0 D to 2.25 D. 80% of the cataract patients had preoperative astigmatism to the levels of 1.0 D and 20% patients 1.25 D and above. On all intervals of study period the SIA range was up to 3.0 D. Postoperatively from day- 1 to week- 6 intervals, SIA not only decreased but also shifted to lower range. Final mean values of SIA were 1.565 ± 0.555 D, 1.425 ± 0.690 D, 1.02 ± 0.686 D, and 0.66 ± 0.67 D on day- 1, week -1, -4 and -6 respectively. The uncorrected visual acuity was 6/36 to 6/18 in 10 (20%) patients and 6/12 to 6/6 in 40 (80%). The best corrected visual acuity was 6/36 to 6/18 in 8 (16%) patients and 6/12 to 6/6 in 42 (84%) patients. [ABSTRACT FROM AUTHOR]