Exploring host genetic polymorphisms involved in SARS-CoV infection autcomes: implications for personalized medicine in COVID-19

Objective. To systematically explore genetic polymorphisms associated with the clinical outcomes in SARS-CoV infection in humans. Methods. This comprehensive literature search comprised available English papers published in PubMed/Medline and SCOPUS databases following the PRISMA-P guidelines and PICO/AXIS criteria. Results. Twenty-nine polymorphisms located in 21 genes were identified as associated with SARS-CoV susceptibility/resistance, disease severity, and clinical outcomes predominantly in Asian populations. Thus, genes implicated in key pathophysiological processes such as the mechanisms related to the entry of the virus into the cell and the antiviral immune/inflammatory responses were identified. Conclusions. Although caution must be taken, the results of this systematic review suggest that multiple genetic polymorphisms are associated with SARS-CoV infection features by affecting virus pathogenesis and host immune response, which could have important applications for the study and understanding of genetics in SARS-CoV-2/COVID-19 and for personalized translational clinical practice depending on the population studied and associated environments

Epigenetic modifications as outcomes of exercise interventions related to specific metabolic alterations: a systematic review

Background: Chronic diseases arise as a consequence of an unhealthy lifestyle primarily characterized by physical inactivity and unbalanced diets. Regular physical activity can improve health, and there is consistent evidence that these improvements may be the result of epigenetic modifications. Objective: To identify epigenetic modificationsas outcomes of exercise interventions related to specific metabolic alterations. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) methodology for manuscript research and preparation was followed using PubMed and EBSCO databases for literature review. Out of 2,638 articles identified, only 34 articles met the inclusion criteria. Results: The sections of the review were organized by metabolic alterations in which studies were grouped according to healthy, diseased, and trained individuals. Resistance exercise in humans induced epigenetic changes in pathways associated with energy metabolism and insulin sensitivity, contributing to healthy skeletal muscle. Endurance exercise also caused modifications in biomarkers associated to metabolic alterations through changes in DNA methylation and the expression of specific miRNAs. However, both resistance and endurance exercise are necessary to obtain a better physiological adaptation and a combination of both seems to be needed to properly tackle the increasing prevalence of non-communicable pathologies. Conclusion: Given the heterogeneity and complexity of the existing literature, it is currently not possible to propose a specific recommendation about the type, intensity, or duration of exercise that could be beneficial for different subsets of the population (healthy, diseased, and/or trained). Nevertheless, this review highlights the importance of exercise for health and shows the need to perform more research in this emerging area to identify epigenetic biomarkers that could serve as indicators of exercise adaptations

DNA methylation in genes of longevity‐regulating pathways: association with obesity and metabolic complications

Aging is the main risk factor for most chronic diseases. Epigenetic mechanisms, such as DNA methylation (DNAm) plays a pivotal role in the regulation of physiological responses that can vary along lifespan. The aim of this research was to analyze the association between leukocyte DNAm in genes involved in longevity and the occurrence of obesity and related metabolic alterations in an adult population. Subjects from the MENA cohort (n=474) were categorized according to age () and the presence of metabolic alterations: increased waist circumference, hypercholesterolemia, insulin resistance, and metabolic syndrome. The methylation levels of 58 CpG sites located at genes involved in longevity‐regulating pathways were strongly correlated (FDR‐ adjusted< 0.0001) with BMI. Fifteen of them were differentially methylated (p<0.05) between younger and older subjects that exhibited at least one metabolic alteration. Six of these CpG sites, located at MTOR (cg08862778), ULK1 (cg07199894), ADCY6 (cg11658986), IGF1R (cg01284192), CREB5 (cg11301281), and RELA (cg08128650), were common to the metabolic traits, and CREB5, RELA, and ULK1 were statistically associated with age. In summary, leukocyte DNAm levels of several CpG sites located at genes involved in longevity‐ regulating pathways were associated with obesity and metabolic syndrome traits, suggesting a role of DNAm in aging‐related metabolic alterations

Epigenome-wide association study in peripheral white blood cells involving insulin resistance

Insulin resistance (IR) is a hallmark of type 2 diabetes, metabolic syndrome and cardiometabolic risk. An epigenetic phenomena such as DNA methylation might be involved in the onset and development of systemic IR. The aim of this study was to explore the genetic DNA methylation levels in peripheral white blood cells with the objective of identifying epigenetic signatures associated with IR measured by the Homeostatic Model Assessment of IR (HOMA-IR) following an epigenome-wide association study approach. DNA methylation levels were assessed using Infinium Methylation Assay (Illumina), and were associated with HOMA-IR values of participants from the Methyl Epigenome Network Association (MENA) project, finding statistical associations for at least 798 CpGs. A stringent statistical analysis revealed that 478 of them showed a differential methylation pattern between individuals with HOMA-IR ≤ 3 and > 3. ROC curves of top four CpGs out of 478 allowed differentiating individuals between both groups (AUC≈0.88). This study demonstrated the association between DNA methylation in some specific CpGs and HOMA-IR values that will help to the understanding and in the development of new strategies for personalized approaches to predict and prevent IR-associated diseases

Complex evolutionary history of the Mexican stoneroller Campostoma ornatum Girard, 1856 (Actinopterygii: Cyprinidae)

<p>Abstract</p> <p>Background</p> <p>Studies of the phylogeography of Mexican species are steadily revealing genetic patterns shared by different species, which will help to unravel the complex biogeographic history of the region. <it>Campostoma ornatum </it>is a freshwater fish endemic to montane and semiarid regions in northwest Mexico and southern Arizona. Its wide range of distribution and the previously observed morphological differentiation between populations in different watersheds make this species a useful model to investigate the biogeographic role of the Sierra Madre Occidental and to disentangle the actions of Pliocene tecto-volcanic processes <it>vs </it>Quaternary climatic change. Our phylogeographic study was based on DNA sequences from one mitochondrial gene (<it>cytb</it>, 1110 bp, n = 285) and two nuclear gene regions (S7 and RAG1, 1822 bp in total, n = 56 and 43, respectively) obtained from 18 to 29 localities, in addition to a morphological survey covering the entire distribution area. Such a dataset allowed us to assess whether any of the populations/lineages sampled deserve to be categorised as an evolutionarily significant unit.</p> <p>Results</p> <p>We found two morphologically and genetically well-differentiated groups within <it>C. ornatum</it>. One is located in the northern river drainages (Yaqui, Mayo, Fuerte, Sonora, Casas Grandes, Santa Clara and Conchos) and another one is found in the southern drainages (Nazas, Aguanaval and Piaxtla). The split between these two lineages took place about 3.9 Mya (CI = 2.1-5.9). Within the northern lineage, there was strong and significant inter-basin genetic differentiation and also several secondary dispersal episodes whit gene homogenization between drainages. Interestingly, three divergent mitochondrial lineages were found in sympatry in two northern localities from the Yaqui river basin.</p> <p>Conclusions</p> <p>Our results indicate that there was isolation between the northern and southern phylogroups since the Pliocene, which was related to the formation of the ancient Nazas River paleosystem, where the southern group originated. Within groups, a complex reticulate biogeographic history for <it>C. ornatum </it>populations emerges, following the taxon pulse theory and mainly related with Pliocene tecto-volcanic processes. In the northern group, several events of vicariance promoted by river or drainage isolation episodes were found, but within both groups, the phylogeographic patterns suggest the occurrence of several events of river capture and fauna interchange. The Yaqui River supports the most diverse populations of <it>C. ornatum</it>, with several events of dispersal and isolation within the basin. Based on our genetic results, we defined three ESUs within <it>C. ornatum </it>as a first attempt to promote the conservation of the evolutionary processes determining the genetic diversity of this species. They will likely be revealed as a valuable tool for freshwater conservation policies in northwest Mexico, where many environmental problems concerning the use of water have rapidly arisen in recent decades.</p

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

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.

The Global Burden of Diseases, Injuries and Risk Factors 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