Disaggregation of amyloid-like protein aggregates isolated from human cataract lens

Crystallins, which represents the major lens protein, play a significant role in ensuring the lens transparency and maintenance of appropriate refractive index of the lens that help in accurate focusing of incident visible light precisely on retina to create clear image perception. Aggregation of lens proteins is known to form the basis of cataract formation. The present study is an attempt to examine the stability of the lens protein aggregates, isolated from human cataract eye lens, against an anionic detergent Sodium dodecyl sulphate (SDS), which is known to disrupt the hydrophobic interaction of protein aggregates. Data that emerged from Congo red (CR), thioflavin T (ThT) and 8-anilino-1-naphthalene sulfonic acid (ANS) binding assaysindicated their amyloidogenic nature. A significant reduction in the bathochromic shift of CR λmax and ThT fluorescence emission intensity were observed after treatment of the aggregated proteins with SDS. In the presence of SDS, a significant change in the number and size of the protein aggregates were observed during their morphological analyses under transmission electron microscopy (TEM). Based on the above data it became evident that the hydrophobic interaction plays a crucial role in formation and stabilizing the protein aggregates during cataract formation

Novel cross linked guar gum-g-poly(acrylate) porous superabsorbent hydrogels: Characterization and swelling behaviour in different environments

A new series of eco-friendly cross linked guar gum-g-poly(acrylate) porous superabsorbent hydrogels was prepared by in situ grafting polymerization and cross-linking on to a natural guar gum employing N,N-methylene bis acrylamide as cross linker. Morphological and structural characterization of the prepared hydrogels (SPHs) done by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and solid state C13 NMR spectroscopy confirmed formation of porous grafted and crosslinked hydrogel structure. Increase in cross linker concentration in the feed mass exhibited decrease in porosity and increase in density of the hydrogels. Swelling of an optimized hydrogel (SPH) in response to external stimuli namely, salt solutions, fertilizer solutions, temperature, and pH exhibited high swelling ratios in various environments. Swelling rate of the SPH was faster than the corresponding nonporous superabsorbent hydrogel. The prepared hydrogels can serve as excellent carriers of pesticides, fertilizers and agriculturally important microbes. Biocontrol formulations based on a representative SPH exhibited excellent shelf-life characteristics and bioefficacy against phytopathogenic fungus Pythium aphanidermatum

Probing the potential of bioactive compounds of millets as an inhibitor for lifestyle diseases: molecular docking and simulation-based approach

Millets are becoming more popular as a healthy substitute for people with lifestyle disorders. They offer dietary fiber, polyphenols, fatty acids, minerals, vitamins, protein, and antioxidants. The nutritional importance of millets leads to the present in-silico study of selective bioactive compounds docked against the targets of lifestyle diseases, viz., diabetes, hypertension, and atherosclerosis using molecular docking and molecular simulations approach. Pharmacokinetic analysis was also carried out to analyse ADME properties and toxicity analysis, drug-likeliness, and finally target prediction for new targets for uncharacterized compounds or secondary targets for recognized molecules by Swiss Target Prediction was also done. The docking results revealed that the bioactive compound flavan-4-ol, among all the 50 compounds studied, best docked to all the four targets of lifestyle diseases, viz., Human dipeptidyl peptidase IV (−5.94 kcal mol−1 binding energy), Sodium-glucose cotransporter-2 (−6.49 kcal mol−1) diabetes-related enzyme, the Human angiotensin-converting enzyme (−6.31 kcal mol−1) which plays a significant role in hypertension, and Proprotein convertase subtilisin kexin type 9 (−4.67 kcal mol−1) for atherosclerosis. Molecular dynamics simulation analysis substantiates that the flavan-4-ol forms a better stability complex with all the targets. ADMET profiles further strengthened the candidature of the flavan-4-ol bioactive compound to be considered for trial as an inhibitor of targets DPPIV, SGLT2, PCSK9, and hACE. We suggest that more research be conducted, taking Flavon-4-ol into account where it can be used as standard treatment for lifestyle diseases

Nano-carrier based drug delivery systems for sustained antimicrobial agent release from orthopaedic cementous material

Total joint replacement (TJR), such as hip and knee replacement, is a popular procedure worldwide. Prosthetic joint infections (PJI) after this procedure have been widely reported, where treatment of such infections is complex with high cost and prolonged hospital stay. In cemented arthroplasties, the use of antibiotic loaded bone cement (ALBC) is a standard practice for the prophylaxis and treatment of PJI. Recently, the development of bacterial resistance by pathogenic microorganisms against most commonly used antibiotics increased the interest in alternative approaches for antimicrobial delivery systems such as nanotechnology. This review summarizes the efforts made to improve the antimicrobial properties of PMMA bone cements using nanotechnology based antibiotic and non-antibiotic delivery systems to overcome drawbacks of ALBC in the prophylaxis and treatment of PJIs after hip and knee replacement

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

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Not AvailableIn Indian agriculture, with increasing population and there is growing demand in food safety and security. Additional agricultural land and resources are of limited availability. The reduction of current yield losses is due to lack of quality seed which is basic input for agriculture. The seed quality plays major role. Seed quality deterioration at different phases due to biotic and abiotic stresses is a major challenge. In this context, a newer concept of seed coating plays a major role. Seed coating achieves better plant establishment and higher yields by innovation in delivery systems of active ingredients, correct use of pesticides and finally reshaping seed microenvironment.Not Availabl