Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test

Chlorpheniramine, a first-generation antihistamine, is widely used for allergic reactions. Previous studies showed the interaction between antidepressant activity and nitric oxide and cyclic guanosine monophosphate (NO/cGMP) pathway. Thus, we aimed to assess the possible involvement of NO/cGMP pathway in this effect using forced swim test (FST) in male mice. To evaluate the locomotor activity and immobility time, we performed open field test (OFT) and FST on each mouse. Chlorpheniramine was administered intraperitoneally (i.p.) (0.1, 0.3, 1, 10 mg/kg) 30 minutes before FST. To assess the involvement of NO/cGMP pathway, a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10mg/kg, i.p.), a selective inducible NOS (iNOS) inhibitor, aminoguanidine (50 mg/kg, i.p.), a selective neural NOS (nNOS) inhibitor, 7-nitroindazole (7-NI, 30 mg/kg, i.p.), a NO precursor, L-arginine (750 mg/kg, i.p.) and a selective phosphodiesterase-5 (PDE-5) inhibitor, sildenafil (5 mg/kg, i.p.) was co-administered with chlorpheniramine. Chlorpheniramine significantly decreased the immobility time at doses of 1mg/kg (P0.05). Moreover, pretreatment with L-arginine (P<0.01) and sildenafil (P<0.001) significantly reduced the anti-immobility effect of chlorpheniramine. These treatments did not alter the locomotor activity of mice in OFT. Our results revealed that the antidepressant-like effect of chlorpheniramine is mediated through inhibition of NO/cGMP pathway

Dietary patterns, nutrition, and risk of breast cancer: a case-control study in the west of Iran

OBJECTIVES Unhealthy dietary patterns are the most important changeable risk factors for breast cancer. The aim of this study was to assess the relationship between dietary patterns and the risk of breast cancer among under-50 year women in the west of Iran. METHODS All women under 50 years old with pathologically confirmed breast cancer between 2013 and 2015 who were referred to oncology clinics in the west of Iran, and 408 under-50 women referred to other outpatient clinics who were without breast or other cancers at the time of the study and 2 years later were selected as the control group. The data were collected using the middle-aged periodical care form of the Iranian Ministry of Health and analyzed using univariate and multivariate logistic regression in Stata. RESULTS The most powerful risk factor for breast cancer was fried foods; the odds ratio of consuming fried foods more than once a month for breast cancer was 4.5 (95% confidence interval, 2.1 to 9.4). A dose-response model indicated that increasing vegetable and fruit consumption up to 90 servings per month decreased the odds of breast cancer, but consuming more than 90 servings per month increased the risk. CONCLUSIONS Inadequate consumption of vegetables and consumption of soft drinks, industrially produced juices, fried foods, and sweets were identified as risk factors for breast cancer. In response to these findings, it is necessary to raise awareness and to provide education about healthy diets and the need to change unhealthy dietary patterns

Non-Pharmacologic Interventions in COVID-19 Pandemic Management; a Systematic Review

Introduction: Different countries throughout the world have adopted non-pharmacologic interventions to reduce and control SARS - CoV-2. In this systematic approach, the impact of non-pharmacologic interventions in management of COVID-19 pandemic was assessed. Methods: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, systematic search was carried out on the basis of a search strategy on PubMed, Web of Science, Scopus, and WHO databases on COVID-19. The impact of travel ban, personal protective equipment, distancing, contact tracing, school closure, and social distancing and the combined effect of interventions on COVID-19 were assessed. Results: Of the 14,857 articles found, 44 were relevant. Studies in different countries have shown that various non-pharmacological interventions have been used during the COVID-19 pandemic. The travel ban, either locally or internationally in most of the countries, movement restriction, social distancing, lockdown, Personal Protective Equipment (PPE), quarantine, school closure, work place closure, and contact tracing had a significant impact on the reduction of mortality or morbidity of COVID-19. Conclusion: Evidence shows that the implementation of non-pharmacologic interventions (NPIs), for example, social distancing, quarantine, and personal protective equipment’s are generally effective and the best way to prevent or reduce transmission. However, this study suggests that the effectiveness of any NPI alone is probably limited, thus, a combination of various actions, for example, social distancing, isolation, and quarantine, distancing in the workplace and use of personal protective equipment, is more effective in reducing COVID-19

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill &amp; Melinda Gates Foundation

Global, regional, and national mortality among young people aged 10-24 years, 1950-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10-24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10-24 years by age group (10-14 years, 15-19 years, and 20-24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10-24 years with that in children aged 0-9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10-24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017). Findings In 2019 there were 1.49 million deaths (95% uncertainty interval 1.39-1.59) worldwide in people aged 10-24 years, of which 61% occurred in males. 32.7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32.1% were due to communicable, nutritional, or maternal causes; 27.0% were due to non-communicable diseases; and 8.2% were due to self-harm. Since 1950, deaths in this age group decreased by 30.0% in females and 15.3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10-14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15-19 years was 1.3% in males and 1.6% in females, almost half that of males aged 1-4 years (2.4%), and around a third less than in females aged 1-4 years (2.5%). The proportion of global deaths in people aged 0-24 years that occurred in people aged 10-24 years more than doubled between 1950 and 2019, from 9.5% to 21.6%. Interpretation Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10-24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Grisel’s syndrome associated with tonsillitis

Non-traumatic subluxation of atlanto-axial joint known as Grisel's syndrome is a rare condition. The pathogenesis of Grisel syndrome in not clear but it seems laxity of cervical ligaments in children and an inflammatory process in neck might cause the syndrome. Here we present a case of Grisel's syndrome, a 9 -year- old boy presented with torticollis and discuss about clinical radiological and treatment aspects of the syndrome. Keywords: Grisel’s syndrome, Tonsilliti

Effect of straw mulch application on agronomic traits and grain yield of common bean (Phaseolus vulgaris L.) cultivars under drought stress

Abstract In order to investigate the agronomic traits and grain yield of common bean (Phaseolus vulgaris L.) cultivars under irrigation and straw mulch treatments, an experiment was conducted as factorial based on randomized complete block design with three replications at the research farm of the Faculty of agriculture, University of Tabriz, Iran in 2012. Treatments were two irrigation levels (60 and 120 mm evaporation from class A pan), two cultivars with different growth habits (akhtar and naz as determinate and indeterminate respectively) and two mulch levels (0 and 2 ton/ha of wheat straw). Results showed that effect of irrigation levels, straw mulch and cultivars were significant on plant height, number of leaf per plant, relative water content (RWC) and grain yield of common been. Normal irrigation and application of straw mulch produced the highest measured traits. Also in normal irrigation, leaf area index (LAI) and chlorophyll contents were significantly increased. Akhtar cultivar had higher LAI than that of Naz. Straw mulch in both irrigation treatments improved agronomic traits and grain yield of common bean cultivars

Adjusting for reverse causation to estimate the effect of obesity on mortality after incident heart failure in the Atherosclerosis Risk in Communities (ARIC) study

OBJECTIVES: The lower mortality rate of obese patients with heart failure (HF) has been partly attributed to reverse causation bias due to weight loss caused by disease. Using data about weight both before and after HF, this study aimed to adjust for reverse causation and examine the association of obesity both before and after HF with mortality. METHODS: Using the Atherosclerosis Risk in Communities (ARIC) study, 308 patients with data available from before and after the incidence of HF were included. Pre-morbid and post-morbid obesity were defined based on body mass index measurements at least three months before and after incident HF. The associations of pre-morbid and post-morbid obesity and weight change with survival after HF were evaluated using a Cox proportional hazard model. RESULTS: Pre-morbid obesity was associated with higher mortality (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.04 to 2.49) but post-morbid obesity was associated with increased survival (HR, 0.57; 95% CI, 0.37 to 0.88). Adjusting for weight change due to disease as a confounder of the obesity-mortality relationship resulted in the absence of any significant associations between post-morbid obesity and mortality. CONCLUSIONS: This study demonstrated that controlling for reverse causality by adjusting for the confounder of weight change may remove or reverse the protective effect of obesity on mortality among patients with incident HF

Adjusting for reverse causation to estimate the effect of obesity on mortality after incident heart failure in the Atherosclerosis Risk in Communities (ARIC) study

OBJECTIVES: The lower mortality rate of obese patients with heart failure (HF) has been partly attributed to reverse causation bias due to weight loss caused by disease. Using data about weight both before and after HF, this study aimed to adjust for reverse causation and examine the association of obesity both before and after HF with mortality. METHODS: Using the Atherosclerosis Risk in Communities (ARIC) study, 308 patients with data available from before and after the incidence of HF were included. Pre-morbid and post-morbid obesity were defined based on body mass index measurements at least three months before and after incident HF. The associations of pre-morbid and post-morbid obesity and weight change with survival after HF were evaluated using a Cox proportional hazard model. RESULTS: Pre-morbid obesity was associated with higher mortality (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.04 to 2.49) but post-morbid obesity was associated with increased survival (HR, 0.57; 95% CI, 0.37 to 0.88). Adjusting for weight change due to disease as a confounder of the obesity-mortality relationship resulted in the absence of any significant associations between post-morbid obesity and mortality. CONCLUSIONS: This study demonstrated that controlling for reverse causality by adjusting for the confounder of weight change may remove or reverse the protective effect of obesity on mortality among patients with incident HF