Embryonic onset of sexually dimorphic heart rates in the viviparous fish, Gambusia holbrooki

In fish, little is known about sex-specific differences in physiology and performance of the heart and whether these differences manifest during development. Here for the first time, the sex-specific heart rates during embryogenesis of Gambusia holbrooki, from the onset of the heart rates (HRs) to just prior to parturition, was investigated using light cardiogram. The genetic sex of the embryos was post-verified using a sex-specific genetic marker. Results reveal that heart rates and resting time significantly increase (p p p p G. holbrooki could serve as a better model to study comparative vertebrate cardiovascular development as well as to investigate anthropogenic and climatic impacts on heart physiology of this species, that may be sex influenced

Air pollution, environmental chemicals, and smoking may trigger vitamin D deficiency: Evidence and potential mechanisms

Beyond vitamin D (VD) effect on bone homeostasis, numerous physiological functions in human health have been described for this versatile prohormone. In 2016, 95% of the world's population lived in areas where annual mean ambient particulate matter (<2.5 μm) levels exceeded the World Health Organization guideline value (Shaddick et al., 2018). On the other hand, industries disperse thousands of chemicals continually into the environment. Further, considerable fraction of populations are exposed to tobacco smoke. All of these may disrupt biochemical pathways and cause detrimental consequences, such as VD deficiency (VDD). In spite of the remarkable number of studies conducted on the role of some of the above mentioned exposures on VDD, the literature suffers from two main shortcomings: (1) an overview of the impacts of environmental exposures on the levels of main VD metabolites, and (2) credible engaged mechanisms in VDD because of those exposures. To summarize explanations for these unclear topics, we conducted the present review, using relevant keywords in the PubMed database, to investigate the adverse effects of exposure to air pollution, some environmental chemicals, and smoking on the VD metabolism, and incorporate relevant potential pathways disrupting VD endocrine system (VDES) leading to VDD. Air pollution may lead to the reduction of VD cutaneous production either directly by blocking ultraviolet B photons or indirectly by decreasing outdoor activity. Heavy metals may reduce VD serum levels by increasing renal tubular dysfunction, as well as downregulating the transcription of cytochrome P450 mixed-function oxidases (CYPs). Endocrine-disrupting chemicals (EDCs) may inhibit the activity and expression of CYPs, and indirectly cause VDD through weight gain and dysregulation of thyroid hormone, parathyroid hormone, and calcium homeostasis. Smoking through several pathways decreases serum 25(OH)D and 1,25(OH)2D levels, VD intake from diet, and the cutaneous production of VD through skin aging. In summary, disturbance in the cutaneous production of cholecalciferol, decreased intestinal intake of VD, the modulation of genes involved in VD homeostasis, and decreased local production of calcitriol in target tissues are the most likely mechanisms that involve in decreasing the serum VD level

Frequency and clinical patterns of stroke in Iran - Systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Cerebrovascular disease is the second commonest cause of death, and over a third of stroke deaths occur in developing countries. To fulfil the current gap on data, this systematic review is focused on the frequency of stroke, risk factors, stroke types and mortality in Iran.</p> <p>Methods</p> <p>Thirteen relevant articles were identified by keyword searching of PubMed, Iranmedex, Iranian University index Libraries and the official national data on burden of diseases.</p> <p>Results</p> <p>The publication dates ranged from 1990 to 2008. The annual stroke incidence of various ages ranged from 23 to 103 per 100,000 population. This is comparable to the figures from Arab Countries, higher than sub-Saharan Africa, but lower than developed countries, India, the Caribbean, Latin America, and China. Similarly to other countries, ischaemic stroke was the commonest subtype. Likewise, the most common related risk factor is hypertension in adults, but cardiac causes in young stroke. The 28-day case fatality rate is reported at 19-31%.</p> <p>Conclusions</p> <p>Data on the epidemiology of stroke, its pattern and risk factors from Iran is scarce, but the available data highlights relatively low incidence of stroke. This may reflect a similarity towards the neighbouring nations, and a contrast with the West.</p

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact