Evidence of apoptosis in some cell types due to pentachlorophenol (PCP) in Heteropneustes fossilis

AbstractThe study aimed to clarify the role of apoptosis in pentachlorophenol (PCP) induced testicular, ovarian and renal cell genotoxicity of Heteropneustes fossilis. It was further intended to find the target germ cell type and assess the cellular and nuclear damage. Treatment of PCP was used for multiduration on the germinal tissues and they were processed to detect structural changes by light and electron microscopic evaluation and kidney cells for subsequent detection of DNA fragmentation by agarose gel electrophoresis. Findings suggest functional and morphological changes in the tissues are due to apoptosis, as evidenced by some biochemical and cytological signs. Histological observation on germinal epithelium reveals cell suicidal symptoms such as vacuolization, liquefied regions in the cytoplasm of oocytes, margination of nuclei, clumping of chromatin, and compaction of cytoplasmic organelle. Biochemical manifestation concurrent to this, is; cleavage of kidney cell DNA into low molecular weight fragments confirming apoptosis. Subsequently, it is further cleaved into nucleosome size fragments or its multiples. Ultra-structural histopathology and DNA studies conclusively lead to the PCP induced apoptosis in the exposed cell types. Results further support the usefulness of this assay in the related studies and its feasibility in generating a base line data

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Improved Utilization of Solar Energy Using Estimated Optimal Tilt Factor and Trackers

This work contributes toward improving the utilization of solar energy. The problem with some of the existing tracking techniques for solar photovoltaic panels is that they have not been put to their best use. In this study, the objective is to optimally use tracking techniques to improve solar energy utilization. The study begins with the solar irradiance data and then proceeds with the definition and mathematical calculations related to the tilt factor. Monthly optimized tilt angles that maximize tilt factor for beam radiation are estimated through mathematical modeling. The net tilt factor is assessed to calculate the tilted global irradiance on tilted PV panels. Different solar tracking techniques like horizontal axis (continuous, daily, weekly and monthly) adjustment, vertical axis continuous adjustment and two-axis are considered to evaluate the response of the 1 kW PV array. The response is evaluated in terms of energy yield using Hybrid Optimization of Multiple Energy Resources (HOMER). The results show that the two-axis tracking system yields the best electrical energy production (2100 kWh/yr), which is 21.28% more than the yield of horizontal axis monthly adjustment (1653 kWh/yr). The extended results further show that if the horizontal axis monthly adjustments are being made using the estimated optimal angles, the energy yield increased from 1653 kWh/yr to 1792 kWh/yr, an increase of 8.40% compared to the HOMER-based calculations. The optimal angles and tilt factor calculations were performed using MATLAB. An additional advantage associated with horizontal axis monthly adjustment is that its implementation is easy, and the associated cost is less than the other tracking techniques. The results obtained can be used further to design PV-based microgrids efficiently

Prevalence and characterization of coronary artery disease in patients with symptomatic bradyarrhythmias requiring pacemaker implantation

Background: This study was conducted to assess the prevalence and characterization of CAD in high risk patients requiring pacemaker implantation for symptomatic bradyarrhythmias. Methods: This study included 100 patients with symptomatic sinus node dysfunction or atrioventricular block, who were at high risk of CAD or had previously documented atherosclerotic vascular disease (ASCVD). Coronary angiography was performed before pacemaker implantation. CAD was defined as the presence of any degree of narrowing in at least one major coronary artery or its first order branch. Obstructive CAD was defined as ≥50% diameter stenosis. CAD was categorized as single vessel disease (SVD), double vessel disease (DVD), or triple vessel disease (TVD); and obstructive CAD in the arteries supplying the conduction system was sub-classified according to Mosseri's classification. Results: Out of 100 patients (mean age 64.6 ± 10.7 years), 45 (45%) had CAD. 29% patients had obstructive CAD while 16% had non-obstructive CAD. 53.3% patients had SVD, 15.6% had DVD and 31.1% had TVD. Among patients with obstructive CAD; Type I, II, III and IV coronary anatomies were present in 6.9%, 34.5%, 10.3% and 48.3% patients respectively. Presence of CAD significantly correlated with dyslipidemia (p = 0.047), history of smoking (p = 0.025), and family history of CAD (p = 0.002). Conclusion: Angiographic CAD is observed in a substantial proportion of patients with symptomatic bradyarrhythmias and risk factors for CAD. It could be argued that such patients should undergo a coronary work-up before pacemaker implantation. Treatment of concomitant CAD is likely to improve the long term prognosis of these patients

Dimethoate Induces DNA Damage and Mitochondrial Dysfunction Triggering Apoptosis in Rat Bone-Marrow and Peripheral Blood Cells

Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2

Role of cardiac magnetic resonance imaging in identifying infarct related artery and non-ischemic pathogenesis in patients presenting with non ST elevation myocardial infarction

Introduction: Identifying an Infarct-related artery (IRA)in Non-STEMI is sometimes tricky. Besides, myocardial infarction with non-obstructive coronary arteries (MINOCA) mimickers are often labeled as myocardial infarction. Late Gadolinium enhancement (LGE) on cardiac MRI can help in identifying IRA besides MINOCA mimickers. Aims: To study the role of LGE on cardiac MRI(CMR) in NSTEMI. Material Methods: It was a prospective observational, double-blinded study. 70 NSTEMI patients were prospectively enrolled over two years. CMR was done before coronary angiography (CAG) during the index hospitalization. Matching was done between IRA selected by CAG and IRA as determined by LGE on MRI. Results: Mean age was 58 ± 15 years. CAG could not identify IRA in 38.6% (n = 27) patients. In this patient group, LGE-CMR identified IRA in 48.1% (n = 13) & a new non-CAD diagnosis was identified in 18.5% (n = 5) patients. IRA was identified in 61.4% (n = 43) by CAG & in this patient group, LGE-CMR identified a different IRA in 6.9% (n = 3) patients. LGE-CMR also identified a new non-CAD diagnosis in 11.6% (n = 5) of patients from this group. Overall, LGE-CMR led to a new IRA diagnosis in 23% (n = 16) patients & a diagnosis of non-ischemic pathogenesis in 14% (n = 10) patients. Non-Ischemic diagnosis on CMR included stress cardiomyopathy in 3, myocarditis in 6, and infiltrative disorder in 1 patient. Conclusion: CMR leads to new IRA diagnoses or non-ischemic pathogenesis in one-third of the cohort

Soil Quality Index as Affected by Integrated Nutrient Management in the Himalayan Foothills

Soil quality assessment serves as an index for appraising soil sustainability under varied soil management approaches. Our current investigation was oriented to establish a minimum data set (MDS) of soil quality indicators through the selection of apt scoring functions for each indicator, thus evaluating soil quality in the Himalayan foothills. The experiment was conducted during two consecutive years, viz. 2016 and 2017, and comprised of 13 treatments encompassing different combinations of chemical fertilizers, organic manure, and biofertilizers, viz. (i) the control, (ii) 20 kg P + PSB (Phosphorus solubilizing bacteria), (iii) 20 kg P + PSB + Rhizobium, (iv) 20 kg P + PSB + Rhizobium+ FYM, (v) 20 kg P + 0.5 kg Mo + PSB, (vi) 20 kg P + 0.5 kg Mo + PSB + Rhizobium, (vii) 20 kg P + 0.5 kg Mo + PSB + Rhizobium + FYM, (viii) 40 kg@ P + PSB, (ix) 40 kg P + PSB + Rhizobium, (x) 40 kg P + PSB + Rhizobium+ FYM, (xi) 40 kg P + 0.5 kg Mo + PSB, (xii) 40 kg P + 0.5 kg Mo + PSB + Rhizobium, and (xiii) 40 kg P + 0.5 kg Mo + PSB + Rhizobium + FYM. Evaluating the physical, chemical, and biological indicators, the integrated module of organic and inorganic fertilization reflected a significant improvement in soil characteristics such as the water holding capacity, available nitrogen, phosphorus, potassium, and molybdenum, different carbon fractions and soil biological characteristics encircling microbial biomass carbon (MBC), and total bacterial and fungal count. A principal component analysis (PCA) was executed for the reduction of multidimensional data ensued by scoring through the transformation of selected indicators. The soil quality index (SQI) established for different treatments exhibited a variation of 0.105 to 0.398, while the magnitude of share pertaining to key soil quality indicators for influencing soil quality index encircled the water holding capacity (WHC), the dehydrogenase activity (DHA), the total bacteria count, and the available P. The treatments that received an integrated nutrient package exhibited a higher SQI (T10—0.398; T13—0.372; T7—0.307) in comparison to the control treatment (T1—0.105). An enhanced soil quality index put forth for all organic treatments reflected an edge of any conjunctive package of reduced synthetic fertilizers with prime involvement of organic fertilizers over the sole application of inorganic fertilizers

IJCM_222A: Assessment of Implementation of Health and Wellness Centers in Kashmir Valley. A Descriptive Study

Background: Health and wellness canters component were launched under the ambit of Ayushman Bharat Yojana. In Kashmir, there was scarce data regarding health and wellness centers implementation therefore this study was undertaken to identify the gaps in implementation of the program at grassroot levels. Objective: to assess and compare the existing staff, services, lab services and infrastructure at health and wellness centers across ten districts of Kashmir valley. Methodology: a descriptive cross-sectional study was done to evaluate the implementation of health and wellness centers in ten districts of Kashmir valley. study population: staff at health and wellness centers study setting: selected health and wellness centers in 10 districts of Kashmir valley sampling: convenient sampling and random sampling 10 % of upgraded health and wellness center in each district at the beginning and 12 months of study. study timeline: 15months data collection 12 months interpretation 3 months study tools: preformed checklist, semi open questionnaires interviews Results: the results of the study indicated that there was still a gap in implementation of program as per guidelines. there were deficiencies in terms of yoga and wellness, proper space for health and wellness centers and staff was not trained properly about the program. Conclusion: this study was done in Kashmir valley to asess the implementation of health and wellness center component of Ayushman Bharat yojana. the study highlighted important deficiencies during the implementation of the program as per guidelines