Impact of Training on Perceived Stress of Parents with Intellectually Disabled Children

The present study focuses on the perceived stress in 353 parents, whose Children with Intellectual disability underwent training in special education schools of (Bavitha Readiness Centres), Chittoor dist., Andhra Pradesh. The overall perceived stress (scale) score was measured through family assessment scheduled (FAS) developed by NIMHANS. The concerned mean scores were computed and compared at two stages of special training given to children i.e., at the time of joining and after two years of training with a paired t-test of significance. The overall findings reveal that the overall score, as well as its four sub–scales score of parent’s perceived stress, have been reduced after providing 2 years of special training to their Children with Intellectual disability as compared to joining the school (training)

Extracellular histones cause vascular necrosis in severe glomerulonephritis

Crescentic glomerulonephritis is characterized by glomerular necrosis. Dying cells release intracellular proteins that act as danger-associated molecular patterns to activate the innate immune system. Previously, we have demonstrated that dying tubular cells release histones, which can kill endothelial cells and activate the toll-like receptor 2/4 (TLR2/4). This drives tubulointerstitial inflammation in septic or post-ischemic acute kidney injury (AKI). Furthermore, other groups have also reported that extracellular histones cause organ damage during acute lung injury, stroke, peritonitis and retinal dysfunction, and that blocking extracellular histones represents a beneficial approach during the disease progression. In this thesis, we investigated whether extracellular histones can elicit similar pathogenic effects during necrotizing glomerulonephritis. To do so, we used an animal model based on the necrotizing type of severe glomerulonephritis. Necrotic glomerulonephritis was induced in mice by a single intravenous injection of 100µl sheep anti-GBM antiserum. The impact of histone neutralization was studied by using an antibody isolated from the BWA-3 clone, which had the capacity to neutralize released extracellular histones in-vivo and in-vitro. After 7 days, mice were sacrificed and kidneys were collected for further data analysis. Proteinuria was assessed in spot urine samples. Anti-GBM treated mice showed increased proteinuria (albumin/creatinine ratio), plasma creatinine and BUN levels. This was associated with a reduced number of podocytes, increased crescentic glomeruli and the infiltration of neutrophils and macrophages into the kidney. Interestingly, neutralization of extracellular histones significantly reduced proteinuria leading to less podocyte damage. This was linked to an improved renal function defined by lower plasma creatinine and BUN levels, and with a decrease in neutrophil and macrophage infiltration and activation in kidney. Histone blockade also significantly reduced renal mRNA expression of TNF-α and fibrinogen in the glomerular capillaries, which was associated with less glomerulosclerosis, crescents and tubular atrophy. In-vitro studies demonstrated that extracellular histones and NETs-related histones kill glomerular endothelial cells, podocytes and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as anti-histone IgG, activated protein C or heparin prevented this cytotoxic effect. Stimulation of BMDCs with histones upregulated the expression of the activation marker including MHC-II, CD48, CD80 and CD86 significantly as well as increased the production of TNF-α and IL-6. It has been previously reported by others including us that in biopsies from patients with ANCA-associated vasculitis showed an over-expression of the TLR2/4 receptor compared to the healthy glomeruli. Histone toxicity on glomeruli ex-vivo was also dependent on the TLR2/4 receptor axis given that the lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-GBM glomerulonephritis involved NET formation and vascular necrosis, while blocking NET formation via PAD inhibitor or pre-emptive anti-histone IgG injection significantly reduced all parameters of glomerulonephritis including vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment and activation of glomerular leukocytes, and glomerular crescent formation. Finally, to evaluate histones as a therapeutic target, mice with established glomerulonephritis were treated with three different histone-neutralizing agents such as anti-histone IgG, recombinant activated protein C and/or heparin. Interestingly, all agents were equally effective in abrogating severe glomerulonephritis, while combination therapy had no additive effect. In summary, the results of this thesis indicate that NET-related histones released during glomerulonephritis elicit cytotoxic and immunostimulatory effects and that neutralizing extracellular histones, therefore, represents a potential therapeutic approach when applied during already established glomerulonephritis

Toll-Like Receptor and Accessory Molecule mRNA Expression in Humans and Mice as Well as in Murine Autoimmunity, Transient Inflammation, and Progressive Fibrosis

The cell type-, organ-, and species-specific expression of the Toll-like receptors (TLRs) are well described, but little is known about the respective expression profiles of their accessory molecules. We therefore determined the mRNA expression levels of LBP, MD2, CD36, CD14, granulin, HMGB1, LL37, GRP94, UNC93b1, TRIL, PRAT4A, AP3B1, AEP and the respective TLRs in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. In addition, the expression profiles in transient tissue inflammation upon renal ischemia-reperfusion injury, in spleens and kidneys from mice with lupus-like systemic autoimmunity, and in progressive tissue fibrosis upon unilateral ureteral obstruction were studied. Several TLR co-factors were specifically regulated during the different phases of these disease entities, suggesting a functional involvement in the disease process. Thus, the organ-and species-specific expression patterns need to be considered in the design and interpretation of studies related to TLR-mediated innate immunity, which seems to be involved in the tissue injury phase, in the phase of tissue regeneration, and in progressive tissue remodelling

Tungsten Oxide-Based Z-Scheme for Visible Light-Driven Hydrogen Production from Water Splitting

The stoichiometric water splitting using a solar-driven Z-scheme approach is an emerging field of interest to address the increasing renewable energy demand and environmental concerns. So far, the reported Z-scheme must comprise two populations of photocatalysts. In the present work, only tungsten oxides are used to construct a robust Z-scheme system for complete visible-driven water splitting in both neutral and alkaline solutions, where sodium tungsten oxide bronze (Na0.56WO3–x) is used as a H2 evolution photocatalyst and two-dimensional (2D) tungsten trioxide (WO3) nanosheets as an O2 evolution photocatalyst. This system efficiently produces H2 (14 μmol h–1) and O2 (6.9 μmol h–1) at an ideal molar ratio of 2:1 in an aqueous solution driven by light, resulting in a remarkably high apparent quantum yield of 6.06% at 420 nm under neutral conditions. This exceptional selective H2 and O2 production is due to the preferential adsorption of iodide (I–) on Na0.56WO3–x and iodate (IO3–) on WO3, which is evidenced by both experiments and density functional theory calculation. The present liquid Z-scheme in the presence of efficient shuttle molecules promises a separated H2 and O2 evolution by applying a dual-bed particle suspension system, thus a safe photochemical process

A study on the left ventricular hypertrophy among the patients of chronic kidney disease stage third to five

Background: In Chronic kidney Disease (CKD) a significant risk factor for mortality is Cardiovascular disease (CVD) and the most prevalent cardiovascular risk factor is left ventricular hypertrophy (LVH). Anemia, hypertension and volume overload are risk factors for LVH in CKD. So, the present was aimed at comparing the risk factors between CKD with and without LVH.Methods: A cross sectional study carried out over a 2 year period in Department Nephrology and General Medicine OPD, MIMS, Vizianagaram, Andhra Pradesh. A total of 120 patients are included in this study and divided in to CKD stage III to V based on estimated GFR. Based on 2D echocardiography data CKD cases are further divided in to CKD with LVH and CKD without LVH.Results: The Left ventricular mass index was significant higher in CKD with LVH (128.89±19.28) when compared with CKD without LVH (108.20±10.28). The left ventricular mass index was noted in more number in stage V of CKD. It is also observed that the left ventricular mass index was negatively correlated with haemoglobin and eGFR and was positively correlated with systolic blood pressure and serum NT-proBNP.Conclusions: Present study finding suggested that the incidence of LVH is higher in CKD patients. LVH was positively correlated with hypertension and NT-proBNP and negatively correlated with anemia and estimated GFR

Environmental Pollution Analysis and Impact Study-A Case Study for the Salton Sea in California

A natural experiment conducted on the shrinking Salton Sea, a saline lake in California, showed that each one foot drop in lake elevation resulted in a 2.6% average increase in PM2.5 concentrations. The shrinking has caused the asthma rate continues to increase among children, with one in five children being sent to the emergency department, which is related to asthma. In this paper, several data-driven machine learning (ML) models are developed for forecasting air quality and dust emission to study, evaluate and predict the impacts on human health due to the shrinkage of the sea, such as the Salton Sea. The paper presents an improved long short-term memory (LSTM) model to predict the hourly air quality (O3 and CO) based on air pollutants and weather data in the previous 5 h. According to our experiment results, the model generates a very good R2 score of 0.924 and 0.835 for O3 and CO, respectively. In addition, the paper proposes an ensemble model based on random forest (RF) and gradient boosting (GBoost) algorithms for forecasting hourly PM2.5 and PM10 using the air quality and weather data in the previous 5 h. Furthermore, the paper shares our research results for PM2.5 and PM10 prediction based on the proposed ensemble ML models using satellite remote sensing data. Daily PM2.5 and PM10 concentration maps in 2018 are created to display the regional air pollution density and severity. Finally, the paper reports Artificial Intelligence (AI) based research findings of measuring air pollution impact on asthma prevalence rate of local residents in the Salton Sea region. A stacked ensemble model based on support vector regression (SVR), elastic net regression (ENR), RF and GBoost is developed for asthma prediction with a good R2 score of 0.978

Development of a fast and flexible generic process for the reduction of nitro compounds

The hydrogenation of aromatic nitro substrates is a frequently used reaction in the multi-step fabrication of active pharmaceutical ingredients (APIs). Today most pharmaceutical production processes are performed in batch mode. In the frame of the C2-campaign speed is an important factor during the production of a multitude of possible API’s. A generic reactor set-up able to be adapted for the transformation of a specific substrate would reduce the development time and thereby the campaign time significantly. In the frame of the EU-project F3-Factory such a flexible and continuous reaction system for this important reaction class able to produce 1-5 kg API is being developed. To allow for an easy and fast adaptation of this process for a range of nitro substrates a substrates adoption methodology (SAM) is also being developed. A literature study of the nature of different reduction methods (H2 gas, H-Donor, CO gas, etc.) led to the conclusion that the liquid phase reduction of aromatic nitro substrates by either hydrogen gas or an H-donor is the most selective method. Following the requirements of that reaction type a flexible and modular reactor for the liquid phase reduction with a heterogeneous slurry catalyst was designed that can be adapted for reduction of a range of nitro compounds. The generic process provides the possibilities of swapping out a reactor or work up technology as required. The equipments of the generic process should be also able to operate at wider range of operational variables making it suitable for a range of substrates. The SAM identifies the necessary changes to a generic process and plant in order to adapt it for a given substrate. The objectives of this presentation is to highlight the design of a generic nitro reduction process and to demonstrate the application of this generic process on a pharmaceutical manufacturing case study involving the nitro reduction of 6-Nitroquinoline

Control of Electrons' Spin Eliminates Hydrogen Peroxide Formation during Water Splitting

The production of hydrogen through water splitting in a photoelectrochemical cell suffers from an overpotential that limits the efficiencies. In addition, hydrogen-peroxide formation is identified as a competing process affecting the oxidative stability of photoelectrodes. We impose spin-selectivity by coating the anode with chiral organic semiconductors from helically aggregated dyes as sensitizers; Zn-porphyrins and triarylamines. Hydrogen peroxide formation is dramatically suppressed, while the overall current through the cell, correlating with the water splitting process, is enhanced. Evidence for a strong spin-selection in the chiral semiconductors is presented by magnetic conducting (mc-)AFM measurements, in which chiral and achiral Zn-porphyrins are compared. These findings contribute to our understanding of the underlying mechanism of spin selectivity in multiple electron-transfer reactions and pave the way toward better chiral dye-sensitized photoelectrochemical cells

Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets. Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. A B. malayi ecdysone receptor ligand-binding domain was developed and used to study the ligand-receptor interactions of these agonists. An excellent correlation between the virtual screening results and the screening assay was observed. Based on both of these approaches, steroidal ecdysone agonists and the diacylhydrazine family of compounds were identified as a fruitful source of potential receptor agonists. In further confirmation of the modeling and screening results, Ponasterone A and Muristerone A, two compounds predicted to be strong ecdysone agonists stimulated expulsion of microfilaria and immature stages from adult parasites. Conclusions The studies validate the potential of the B. malayi ecdysone receptor as a drug target and provide a means to rapidly evaluate compounds for development of a new class of drugs against the human filarial parasites

Magnetization switching in ferromagnets by adsorbed chiral molecules without current or external magnetic field

Ferromagnets are commonly magnetized by either external magnetic fields or spin polarized currents. The manipulation of magnetization by spin-current occurs through the spin-transfer-torque effect, which is applied, for example, in modern magnetoresistive random access memory. However, the current density required for the spin-transfer torque is of the order of 1 × 106 A·cm−2, or about 1 × 1025 electrons s−1 cm−2. This relatively high current density significantly affects the devices’ structure and performance. Here we demonstrate magnetization switching of ferromagnetic thin layers that is induced solely by adsorption of chiral molecules. In this case, about 1013 electrons per cm2 are sufficient to induce magnetization reversal. The direction of the magnetization depends on the handedness of the adsorbed chiral molecules. Local magnetization switching is achieved by adsorbing a chiral self-assembled molecular monolayer on a gold-coated ferromagnetic layer with perpendicular magnetic anisotropy. These results present a simple low-power magnetization mechanism when operating at ambient conditions