Effect of Allium Sativum on the Alcohol Induced Neuropathic Pain in Wistar Rats

Neuropathic pain is a severe pain condition associated with pathological changes which have deleterious effects like dysfunction of the brain. Alcohol abuse is known to be the most common reason at present for developing neuropathic pain. Alcohol-induced neuropathic pain can be assessed by ache studies such as hyperalgesia and allodynia which characterizes the response severity of induced pain. In the current research, we used the Allium Sativum (Garlic) bulb extract to study the effect on alcohol-administered rodents. The behavioral and biochemical studies have been done. It has been reported in the study, that Allium sativum has certain protective mechanisms such as analgesic and anti-inflammatory effects, free radical scavenger, and antioxidant effects which contribute to alcohol-induced neuropathic pain. Based on the results of the current investigation, it can be concluded that Allium sativum bulb extract, administered at doses of 200 and 300 mg/kg in 0.9 per cent saline, is helpful in reducing the symptoms of alcoholic neuropathy. Allium sativum may offer a protective effect in the revocation of alcoholic-induced neuropathic pain

A study on innovativeness and regulating conflicts between the fishers and farmers in the Balua wetland

Wetlands store ground and surface water even when the rainfall is erratic. However, the rising demand for water and land to sustain the ever increasing population has manifested in many kinds of conflicts in wetlands. In the study area, Balua Chaur (wetland) in Bihar state of India, 16 conflicts emerged when the flooded lands offarmers was accessed by the fishers to fish. Such conflicts had further marginalized the already indigent fishers. Factor analysis, to reduce the socioeconomic and psychological variables of the fishers that were associated with innovativeness and further analysis of ANOVA and regression was used. In case of fishers, two major groups of interrelated variables that accounted for 60.6 % of the total variance were identified through this method. Factor 1 accounted for 34.8 % of the total variance that included innovativeness, income, education, mass media exposure, extension contact, livestock ownership, land ownership, mobile use collaborating and competing style of conflict management and named as innovative factors. The ANOVA table and stepwise multiple regression model exhibited that the nuclear family type and livestock have significant impact on the innovativeness of fishers with R2 value 0.255. In this paper, peace and prosperity model based upon the analysis of primary information collected from the fishers, farmers and key informants is proposed to foster innovativeness to enhance the productivity of wetland and resolve conflict to mobilize the resources in efficient and judicial manner

ASSOCIATION AND CORRELATION OF MEAN PLATELET VOLUME AND PLATELET COUNT IN ACUTE ISCHEMIC STROKE

Objective: Role of platelets in the pathogenesis of the atherothrombosis and ischemic stroke has been documented. Mean platelet volume (MPV) and platelet count (PC) could be important predictors of acute ischemic stroke (AIS), its severity; therefore we investigated the correlation of MPV & PC in AIS patients. Methods: We studied MPV and PC of 52 AIS patients consecutively admitted in Neurology department at Geetanjali Medical University, India. Platelet variables were measured and compared with control of similar age, sex and without vascular events. Results: Out of 52 patients, 30 (57.69%) had Thirty (57.69%) patients had significantly higher MPV in AIS group (12.45fL compared with normal range of 6–11 fL in control,p<0.001). No significant differences were found between male and females, but the total mean was elevated. The mean of PC was 1.76×105 cells/cumm (normal range) and there was no correlation between the change in PC and AIS in both sexes. Repeated measurements of MPV and PC were also recorded on follow-up which showed no significant changes from the acute phase; however, MPV remained elevated. The comparison of MPV in patients with mRS score 2 versus 4, 2 versus 5, 3 versus 4 and 5, and 4 versus 5 were found to be statistically significant (p<0.05). Conclusion: Increased MPV has an independent association with AIS and its severity and it could not change after acute treatment. It is possible that these changes precede the vascular event, and further studies are warranted to unravel the underlying mechanism

A STUDY OF SEVERITY OF STROKE AND HOMOCYSTEINE LEVEL IN SOUTHERN PART OF RAJASTHAN, INDIA

Objective: Till date, a very few prospective studies have examined the association between serum homocysteine levels and the risk of stroke and stroke subtypes in Indian populations. Methods: A prospective, case - control study of Indian subjects 10–90 years of age was conducted using frozen serum samples from 103 participants in cardiovascular risk surveys collected from December 2017 to November 2018. By the end of 103, we identified 55 incidents of severe strokes, one control subject per case was selected by matching for sex, age, community, year of serum storage, and fasting status. Serum total homocysteine levels were measured by Cobas c-311. Results: Compared with control subjects, total (n_206), hemorrhagic (n_106), and ischemic (n_87) strokes had higher geometric mean values of total homocysteine and higher proportions of homocysteine −25.0 μ mol/L. Homocysteine was estimated after adjustment for body mass index, smoking, alcohol intake, hypertension, and other cardiovascular risk factors. The excess risk of total and ischemic strokes did not vary significantly according to sex, age, smoking status, or hypertensive status. Conclusion: High total homocysteine concentrations were associated with the increased risk of total stroke, more specifically ischemic stroke) Capsuloganglionic and frontoparietal infarct (8 each)., among Indian men and women

MELATONIN AMELIORATES FLUORIDE INDUCED NEUROTOXICITY IN YOUNG RATS: AN IN VIVO EVIDENCE

Objective: Developing brain is highly vulnerable to environmental toxins. Recently, fluoride was declared as a developmental neurotoxin and heralded search for natural neuroprotectant. In the present study, we have evaluated the neuroprotective and anti-inflammatory efficacy of melatonin in fluoride induced neurotoxicity.Methods: Animals were divided into following groups; the first group was used as control. Groups 2, 3 and 4 were treated with melatonin (10 mg/kg BW), sodium fluoride (NaF 4 mg/kg BW) and NaF (4 mg/kg BW) plus melatonin (10 mg/kg BW) respectively. Young rats were orally administered their respective doses daily for 60 days. Biochemical and behavioral analysis were performed. The level of proinflammatory cytokine, tumor necrosis factor alpha (TNF-a) was also determined.Results: Data obtained showed that NaF significantly (p<0.001) increased thiobarbituric acid reactive substances (TBARS), ROS concentration and decreased the activities of glutathione (GSH) and glutathione peroxidase (GPx). On the other hand, melatonin plus NaF treated group showed significant decrease in the levels of TBARS and ROS while it increased the activities of antioxidant enzymes and glutathione content. In addition, melatonin significantly attenuated fluoride-induced increase in the TNF-α level of brain. Melatonin also prevented the cognitive deficit as shown by the increased retention latency in the passive avoidance task (p<0.001).Conclusion: The present study suggests that melatonin has therapeutic potential since it suppresses fluoride induced inflammation, cognitive impairment and oxidative stress in the brain. Key words: Oxidative stress, Inflammation, Melatonin, TNF- α, Fluoride

Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells

Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression

Evaluation of flubendiamide-induced mitochondrial dysfunction and metabolic changes in Helicoverpa armigera (Hubner)

Phthalic acid diamide insecticides are the most effective insecticides used against most of the lepidopteran pests including Helicoverpa armigera, a polyphagous pest posing threat to several crops worldwide. The present studies were undertaken to understand different target sites and their interaction with insect ryanodine receptors (RyR). Bioassays indicated that flubendiamide inhibited the larval growth in dose-dependent manner with LD50 value of 0.72 μM, and at 0.8 μM larval growth decreased by about 88%. Flubendiamide accelerated the Ca2+-ATPase activity in dose-dependent trend, and at 0.8 μM, the activity was increased by 77.47%. Flubendiamide impedes mitochondrial function by interfering with complex I and F0F1-ATPase activity, and at 0.8 μM the inhibition was found to be about 92% and 50%, respectively. In vitro incubation of larval mitochondria with flubendiamide induced the efflux of cytochrome c, indicating the mitochondrial toxicity of the insecticide. Flubendiamide inhibited lactate dehydrogenase and the accumulation of H2O2, thereby preventing the cells from lipid peroxidation compared to control larvae. At 0.8 μM the LDH, H2O2 content and lipid peroxidation was inhibited by 98.44, 70.81, and 70.81%, respectively. Cytochrome P450, general esterases, AChE, and antioxidant enzymes (catalase and superoxide dismutase) exhibited a dose-dependent increasing trend, whereas alkaline phosphatase and the midgut proteases, except amino peptidase, exhibited dose-dependent inhibition in insecticide-fed larvae. The results suggest that flubendiamide induced the harmful effects on the growth and development of H. armigera larvae by inducing mitochondrial dysfunction and inhibition of midgut proteases, along with its interaction with RyR

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury