The effect of boldenone anabolic steroid, and endurance and resistance training on liver damage markers in rats

Background: This study aimed at investigating the effect of boldenone, and endurance and resistance training on liver damage in rats. Materials and Methods: In this study, 70 male Wistar rats aged 12 weeks (weight, 228±7 g) were randomly divided into 10 equal groups: control, sham, boldenone (2 mg/kg), boldenone (5 mg/kg), resistance training, resistance training-boldenone (2 mg/kg), resistance training-boldenone (5 mg/kg), endurance training, endurance training-boldenone (2 mg/kg) and endurance training-boldenone (5 mg/kg) groups. The resistance training program included an 8-week climb from the ladder, three times a week and each session 3 sets with 5 repetitions and the endurance training program was 8-week running on treadmills, 3 days a week, every day 30 minutes at a speed of 12 meters per minute. The injection was performed in the biceps femoris muscle once a week. After anesthesia, autopsy was performed and the liver tissue was isolated for histological studies. Results: The most liver tissue damage was observed in the boldenone group without training; so that the vacuolar degeneration more than 66 and the presence of 1-3 necrotic cells was very important. In resistance training and high-dose boldenone resistance training, liver damage was also observed as vacuolar degeneration. In the endurance training-boldenone inflammation group, increased kupffer cells and mild vacuolar degeneration were observed. Histological studies showed that endurance training reduced the vacuolar degeneration and inflammation and did not increase kupffer cells. Conclusion: It seems that boldenone can cause damage to liver and endurance training compared with resistance training may cause more reduction in liver damage, especially reduction in the vacuolar degeneration and inflammation induced by boldenone

Adjunctive Local Application of Lidocaine during Scleral Buckling under General Anesthesia

Purpose: To evaluate the effect of local lidocaine application on the incidence of the oculocardiac reflex (OCR) during scleral buckling (SB) for rhegmatogenous retinal detachment (RRD) under general anesthesia. Methods: In a randomized clinical trial, eyes with RRD scheduled for SB under general anesthesia were randomized to adjunctive local application of 1 ml lidocaine 2% versus normal saline to the muscles after conjunctival opening. Surgical stimulation was initiated 5 minutes afterwards. Additionally, 100 mg of lidocaine 2% was added to 50 ml of normal saline in the treatment group which was used for irrigation during surgery; control eyes were irrigated with normal saline. The incidence of the OCR, rate of postoperative nausea/vomiting (PONV), total intravenous (IV) analgesic dose, duration of surgery, and period of hospitalization were compared between the study groups. Results: Thirty eyes of 30 patients including 22 (73.3%) male and 8 (26.7%) subjects with mean age of 49.4΁16.3 years were operated. OCR and PONV occurred less frequently, and total intravenous analgesic dose was significantly lower in the lidocaine group (P < 0.05 for all comparisons). However, no significant difference was noted between the study groups in terms of duration of surgery and period of hospitalization. Conclusion: Adjunctive local application of lidocaine during SB under GA for RRD decreases the rate of OCR and PONV, reduces the intravenous analgesic dose, but does not affect the duration of surgery or hospitalization

Status of Central Libraries at Iranian Universities of Medical Sciences for Joining an Integrated Network of Medical Libraries

The aim of the study is to offer integrated access to information and data sources in the libraries of Iranian universities of medical sciences (UMS) as an important feature enhancing the quality and quantity of research. Thus, it is essential to study the status of Iranian libraries of UMS in terms of integration features. Accordingly, the main objective of the present study was the identification of integration in libraries of Iranian UMS in terms of metadata, digital contents, software, hardware, and human force. The quantitative study was conducted with an analytic survey method. The statistical population consists of 66 Iranian UMS, of this, 59 libraries completed the researcher-made questionnaire. To ensure the accuracy of data, interviews and, in some cases, observations were also performed. Statistical estimates of frequency, percentage, cumulative frequency, and diagrams were utilized for data analysis. The results demonstrated that the library software programs of UMS do not have a desirable status in terms of content, human force, software infrastructure, and integration features. These libraries enjoyed an optimal status in terms of hardware which was, however, not properly used. To create integrated access to the contents of libraries of Iranian UMS, it is essential to provide the required infrastructure, including integration features, human force, and appropriate contents such as the metadata and digital contents of data source

Hydrological and associated biogeochemical consequences of rapid global warming during the Paleocene-Eocene Thermal Maximum

The Paleocene-Eocene Thermal Maximum (PETM) hyperthermal, ~ 56 million years ago (Ma), is the most dramatic example of abrupt Cenozoic global warming. During the PETM surface temperatures increased between 5 and 9 °C and the onset likely took < 20 kyr. The PETM provides a case study of the impacts of rapid global warming on the Earth system, including both hydrological and associated biogeochemical feedbacks, and proxy data from the PETM can provide constraints on changes in warm climate hydrology simulated by general circulation models (GCMs). In this paper, we provide a critical review of biological and geochemical signatures interpreted as direct or indirect indicators of hydrological change at the PETM, explore the importance of adopting multi-proxy approaches, and present a preliminary model-data comparison. Hydrological records complement those of temperature and indicate that the climatic response at the PETM was complex, with significant regional and temporal variability. This is further illustrated by the biogeochemical consequences of inferred changes in hydrology and, in fact, changes in precipitation and the biogeochemical consequences are often conflated in geochemical signatures. There is also strong evidence in many regions for changes in the episodic and/or intra-annual distribution of precipitation that has not widely been considered when comparing proxy data to GCM output. Crucially, GCM simulations indicate that the response of the hydrological cycle to the PETM was heterogeneous – some regions are associated with increased precipitation – evaporation (P – E), whilst others are characterised by a decrease. Interestingly, the majority of proxy data come from the regions where GCMs predict an increase in PETM precipitation. We propose that comparison of hydrological proxies to GCM output can be an important test of model skill, but this will be enhanced by further data from regions of model-simulated aridity and simulation of extreme precipitation events

Antioxidative and anti-inflammatory impact of valsartan against renal ischemia-reperfusion injury; role of nitric oxide signaling pathway

Introduction: Renal ischemia reperfusion injury is one of the main causes of acute renal failure, which is associated with high mortality. Tissue damage caused by ischemia-reperfusion occurs due to the release of oxygen free radicals. Type I angiotensin receptor antagonists such as valsartan can be useful in the treatment of chronic kidney disease and hypertension. Objectives: We aimed to evaluate the protective effect of valsartan against renal ischemia reperfusion via antioxidant property and nitric oxide (NO) signaling pathway. Materials and Methods: Fifty male Wistar rats (220 +/- 10 g) were randomly divided into five groups as follows: Group 1; healthy rats without ischemia-reperfusion (control group). Group 2; rats with ischemia reperfusion (IR) (IR control group). Group 3; rats with IR which received 30 mg/kg valsartan orally. Group 4; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-NAME. Group 5; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-arginine. To induce ischemia-reperfusion, rats were anesthetized with thiopental and underwent surgery. Then, we induced ischemia with blocking blood vessels for 45 minutes by clamping. Biochemical parameters including urea and creatinine were measured using commercial kits. Oxidative stress and inflammatory parameters were measured by ELISA method. Renal tissues were stained with hematoxylin and eosin. Finally, the Kolmogorov-Smirnov test was used to determine the normal distribution of data. Results: The findings of this study indicated that treatment with valsartan and valsartan plus L-arginine leads to significant decrease in the serum levels of creatinine, urea, and albumin/creatinine, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in contrast to IR control group which has increased level of these parameters. On the other hand, treatment with valsartan and valsartan plus L-arginine lead to increase in the serum levels of glutathione peroxidase (GPX), in contrast to ischemia reperfusion control group. Conclusion: Our data revealed that valsartan as a type I angiotensin receptor antagonist could decrease oxidative stress and inflammation due to renal ischemia reperfusion injury. Hence, valsartan could propose as a therapeutic agent for kidney diseases such as renal ischemia-reperfusion injury regarded to these renoprotective effects. Keywords Author Keywords:Valsartan; Renal ischemia reperfusion; Antioxidant property; Kidney; Acute renal failure; Reactive oxygen species KeyWords Plus:KIDNEY-DISEASE; HYPERTENSIO

A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis

PURPOSE: A two-stage genome-wide association study was carried out in head and neck cancer (HNC) patients aiming to identify genetic variants associated with either specific radiotherapy-induced (RT) toxicity endpoints or a general proneness to develop toxicity after RT.MATERIALS AND METHODS: The analysis included 1780 HNC patients treated with primary RT for laryngeal or oro/hypopharyngeal cancers. In a non-hypothesis-driven explorative discovery study, associations were tested in 1183 patients treated within The Danish Head and Neck Cancer Group. Significant associations were later tested in an independent Dutch cohort of 597 HNC patients and if replicated, summary data obtained from discovery and replication studies were meta-analysed. Further validation of significantly replicated findings was pursued in an Asian cohort of 235 HNC patients with nasopharynx as the primary tumour site.RESULTS: We found and replicated a significant association between a locus on chromosome 5 and mucositis with a pooled OR for rs1131769*C in meta-analysis = 1.95 (95% CI 1.48-2.41; ppooled = 4.34 × 10-16).CONCLUSION: This first exploratory GWAS in European cohorts of HNC patients identified and replicated a risk locus for mucositis. A larger Meta-GWAS to identify further risk variants for RT-induced toxicity in HNC patients is warranted.</p

Meta-GWAS identifies the heritability of acute radiation-induced toxicities in head and neck cancer

Background and purpose: We aimed to the genetic components and susceptibility variants associated with acute radiation-induced toxicities (RITs) in patients with head and neck cancer (HNC). Materials and methods: We performed the largest meta-GWAS of seven European cohorts (n = 4,042). Patients were scored weekly during radiotherapy for acute RITs including dysphagia, mucositis, and xerostomia. We analyzed the effect of variants on the average burden (measured as area under curve, AUC) per each RIT, and standardized total average acute toxicity (STATacute) score using a multivariate linear regression. We tested suggestive variants (p < 1.0x10-5) in discovery set (three cohorts; n = 2,640) in a replication set (four cohorts; n = 1,402). We meta-analysed all cohorts to calculate RITs specific SNP-based heritability, and effect of polygenic risk scores (PRSs), and genetic correlations among RITS. Results: From 393 suggestive SNPs identified in discovery set; 37 were nominally significant (preplication < 0.05) in replication set, but none reached genome-wide significance (pcombined < 5 × 10-8). In-silico functional analyses identified “3′-5'-exoribonuclease activity” (FDR = 1.6e-10) for dysphagia, “inositol phosphate-mediated signalling” for mucositis (FDR = 2.20e-09), and “drug catabolic process” for STATacute (FDR = 3.57e-12) as the most enriched pathways by the RIT specific suggestive genes. The SNP-based heritability (±standard error) was 29 ± 0.08 % for dysphagia, 9 ± 0.12 % (mucositis) and 27 ± 0.09 % (STATacute). Positive genetic correlation was rg = 0.65 (p = 0.048) between dysphagia and STATacute. PRSs explained limited variation of dysphagia (3 %), mucositis (2.5 %), and STATacute (0.4 %). Conclusion: In HNC patients, acute RITs are modestly heritable, sharing 10 % genetic susceptibility, when PRS explains < 3 % of their variance. We identified numerus suggestive SNPs, which remain to be replicated in larger studies

Large-Scale Meta-GWAS Reveals Common Genetic Factors Linked to Radiation-Induced Acute Toxicities across Cancers

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity (RIT) across four cancer types (prostate, head and neck, breast, and lung).METHODS: A GWAS meta-analysis was performed using 19 cohorts including 12,042 patients. Acute standardized total average toxicity (rSTATacute) was modelled using a generalized linear regression model for additive effect of genetic variants adjusted for demographic and clinical covariates. LD score regression estimated shared SNP-based heritability of rSTATacute in all patients and for each cancer type.RESULTS: Shared SNP-based heritability of STATacute among all cancer types was estimated at 10% (se = 0.02), and was higher for prostate (17%, se = 0.07), head and neck (27%, se = 0.09), and breast (16%, se = 0.09) cancers. We identified 130 suggestive associated SNPs with rSTATacute (5.0x10-8&lt;P-value&lt;1.0x10-5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size -0.17; P-value=1.7x10-7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 x10-6, Pcorrected =0.079) as the top gene set associated with rSTATacute among all patients. In-silico gene expression analysis showed the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed Pcorrected=0.004; sun exposed Pcorrected=0.026).CONCLUSIONS: There is shared SNP-based heritability for acute RIT across and within individual cancer sites. Future meta-GWAS among large radiotherapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.</p

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe