IN VIVO RADIOPROTECTIVE EFFECTS OF WHEATGRASS (TRITICUM AESTIVUM) EXTRACT AGAINST X-IRRADAITION-INDUCED OXIDATIVE STRESS AND APOPTOSIS IN PERIPHERAL BLOOD LYMPHOCYTES IN RATS

 Objectives: The present study was undertaken to investigate the possible protective potential of wheatgrass extract against radiation-induced toxicity in peripheral lymphocytes of rats exposed to a fractionated dose of X-rays.Methods: Effects of the X-irradiation with and without wheatgrass were studied on various parameters in peripheral lymphocytes including antioxidant defense system and apoptosis. Male Sprague-Dawley rats were divided into four different groups: Normal control group, X-ray-irradiated group (21 Gy over a span of 7 days), wheatgrass-treated group (80 mg/100 g bodyweight for 2 weeks), and X-rays-irradiated + wheatgrass-treated group. All the biochemical indices which included lipid peroxidation (LPO), reduced glutathione, reactive oxygen species (ROS), and activities of antioxidant enzymes were investigated in lymphocytes. Terminal deoxynucleotidyl transferase dUTP nick-end labeling assay was carried out to assess the apoptosis in lymphocytes following whole-body X-irradiation.Results: Whole-body X-irradiation to rats resulted in significant increase in LPO with concomitant depression of antioxidant enzymes activities, namely, superoxide dismutase, catalase, and glutathione peroxidise (GPx) in lymphocytes. Further, the present study witnessed a significant increase in the number of apoptotic lymphocytes in the X-irradiated animals. However, wheatgrass supplementation lowered the LPO levels, restored cellular antioxidant status, and provided significant protection against radiation-induced apoptosis.Conclusions: Based on these observations, the present study suggests that wheatgrass extract has the potential to be used as an effective radioprotectant against radiation-induced oxidative stress and apoptosis in peripheral lymphocytes of whole-body X-ray-exposed rats

The Intersection of Diabetes and Cardiovascular Disease—A Focus on New Therapies

Diabetes is a leading cause of cardiovascular disease and its associated morbidity. While the medical community has had access to numerous glucose lowering therapies over the last decades, it was not until recently that newer agents demonstrated improvement in cardiovascular outcomes. In particular, diabetes care and management of its attendant cardiovascular risk is now being revolutionized with the development and provision of the SGLT-2 inhibitors and GLP1-receptor agonists. Given the exciting data with these new classes of diabetes therapeutics, there is a clear need to improve education and utilization of these evidence-based medications across a wide spectrum of clinicians, including cardiologists. The aim of this review is to familiarize the cardiovascular specialist with the benefits and harms of the most commonly used oral anti- hyperglycemic medications, with an emphasis on SGLT-2 inhibitors and GLP-1 receptor agonists

Molecular mechanisms underlying the effects of statins in the central nervous system

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins’ effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins’ effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins’ possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed

Effects of self-management program as adjunctive to usual rehabilitation exercise on pain and functional outcomes in knee osteoarthritis: a randomized controlled trial

Background:Home-basedexercise(HBE)andpatient education (EDU) have been reported asbeneficial additions to usual knee osteoarthritis (KOA) rehabilitation. However, previous trials mostly examined the effects of HBE and EDU separately. Thus, this study aimed to evaluate the effects of a structured combined HBE and EDU program in addition to usual KOA rehabilitation on pain score, functional mobility, and disability level. Study Design: A parallel-group, single-blinded randomized controlled trial. Methods: Eighty adults with KOA were randomly allocated to experimental (n=40) and control (n=40) groups. All participants underwent their usual physiotherapy care weekly for eight weeks. The experimental group received a structured HBE+EDU program to their usual care, while the control group performed home stretching exercises to equate treatment time. The Knee Injury and Osteoarthritis Outcome Score (KOOS) for the disability level, visual analogue scale (VAS) for pain, and timed up-and-go test (TUG) for mobility were measured pre-post intervention. Results: After eight weeks, the experimental group demonstrated significant improvements in the KOOS (all subscales), pain VAS, and TUG scores compared to baseline (P < 0.001); meanwhile, only KOOS (activities of daily living and sports subscales) was significant in the control group. Relative to the control, the experimental group presented higher improvements (P<0.001) by 22.2%, 44.1%, and 15.7% for KOOS, pain VAS, and TUG, respectively. Conclusion: Integrating the HBE+EDU program into usual KOA rehabilitation could reduce pain and disability, while it improved functional mobility. The finding of this study suggests a combination of a structured HBE and EDU program to be considered as part of mainstream KOA management

Evidence-based national vaccine policy

India has over a century old tradition of development and production of vaccines. The Government rightly adopted self-sufficiency in vaccine production and self-reliance in vaccine technology as its policy objectives in 1986. However, in the absence of a full-fledged vaccine policy, there have been concerns related to demand and supply, manufacture vs. import, role of public and private sectors, choice of vaccines, new and combination vaccines, universal vs. selective vaccination, routine immunization vs. special drives, cost-benefit aspects, regulatory issues, logistics etc. The need for a comprehensive and evidence based vaccine policy that enables informed decisions on all these aspects from the public health point of view brought together doctors, scientists, policy analysts, lawyers and civil society representatives to formulate this policy paper for the consideration of the Government. This paper evolved out of the first ever ICMR-NISTADS national brainstorming workshop on vaccine policy held during 4-5 June, 2009 in New Delhi, and subsequent discussions over email for several weeks, before being adopted unanimously in the present form

Using Microsatellites to Understand the Physical Distribution of Recombination on Soybean Chromosomes

Soybean is a major crop that is an important source of oil and proteins. A number of genetic linkage maps have been developed in soybean. Specifically, hundreds of simple sequence repeat (SSR) markers have been developed and mapped. Recent sequencing of the soybean genome resulted in the generation of vast amounts of genetic information. The objectives of this investigation were to use SSR markers in developing a connection between genetic and physical maps and to determine the physical distribution of recombination on soybean chromosomes. A total of 2,188 SSRs were used for sequence-based physical localization on soybean chromosomes. Linkage information was used from different maps to create an integrated genetic map. Comparison of the integrated genetic linkage maps and sequence based physical maps revealed that the distal 25% of each chromosome was the most marker-dense, containing an average of 47.4% of the SSR markers and 50.2% of the genes. The proximal 25% of each chromosome contained only 7.4% of the markers and 6.7% of the genes. At the whole genome level, the marker density and gene density showed a high correlation (R2) of 0.64 and 0.83, respectively with the physical distance from the centromere. Recombination followed a similar pattern with comparisons indicating that recombination is high in telomeric regions, though the correlation between crossover frequency and distance from the centromeres is low (R2 = 0.21). Most of the centromeric regions were low in recombination. The crossover frequency for the entire soybean genome was 7.2%, with extremes much higher and lower than average. The number of recombination hotspots varied from 1 to 12 per chromosome. A high correlation of 0.83 between the distribution of SSR markers and genes suggested close association of SSRs with genes. The knowledge of distribution of recombination on chromosomes may be applied in characterizing and targeting genes

What do we know about chronic kidney disease in India: first report of the Indian CKD registry

<p>Abstract</p> <p>Background</p> <p>There are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics.</p> <p>Methods</p> <p>Data was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively.</p> <p>Results</p> <p>The mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology.</p> <p>Conclusions</p> <p>This report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.</p

Analysis of the Maize dicer-like1 Mutant, fuzzy tassel, Implicates MicroRNAs in Anther Maturation and Dehiscence

Sexual reproduction in plants requires development of haploid gametophytes from somatic tissues. Pollen is the male gametophyte and develops within the stamen; defects in the somatic tissues of the stamen and in the male gametophyte itself can result in male sterility. The maize fuzzy tassel (fzt) mutant has a mutation in dicer-like1 (dcl1), which encodes a key enzyme required for microRNA (miRNA) biogenesis. Many miRNAs are reduced in fzt, and fzt mutants exhibit a broad range of developmental defects, including male sterility. To gain further insight into the roles of miRNAs in maize stamen development, we conducted a detailed analysis of the male sterility defects in fzt mutants. Early development was normal in fzt mutant anthers, however fzt anthers arrested in late stages of anther maturation and did not dehisce. A minority of locules in fzt anthers also exhibited anther wall defects. At maturity, very little pollen in fzt anthers was viable or able to germinate. Normal pollen is tricellular at maturity; pollen from fzt anthers included a mixture of unicellular, bicellular, and tricellular pollen. Pollen from normal anthers is loaded with starch before dehiscence, however pollen from fzt anthers failed to accumulate starch. Our results indicate an absolute requirement for miRNAs in the final stages of anther and pollen maturation in maize. Anther wall defects also suggest that miRNAs have key roles earlier in anther development. We discuss candidate miRNAs and pathways that might underlie fzt anther defects, and also note that male sterility in fzt resembles water deficit-induced male sterility, highlighting a possible link between development and stress responses in plants.ECU Open Access Publishing Support Fun

Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

Background: chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. Methods: we randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. Results: the median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Conclusions: ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.)

Idarubicin dose escalation during consolidation therapy for adult acute myeloid leukemia

Purpose Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and Methods Patients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m daily for 5 days, etoposide 75 mg/m daily for 5 days, and idarubicin 9 mg/m daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). Results Two hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3–internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation (P, .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm (P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3–internal tandem duplication and NPM1 gene mutation subgroups. Conclusion An increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity