Physical and ecological isolation contribute to maintain genetic differentiation between fire salamander subspecies.

Landscape features shape patterns of gene flow among populations, ultimately determining where taxa lay along the continuum between panmixia to complete reproductive isolation. Gene flow can be restricted, leading to population differentiation in two non-exclusive ways: "physical isolation", in which geographic distance in combination with the landscape features restricts movement of individuals promoting genetic drift, and "ecological isolation", in which adaptive mechanisms constrain gene flow between different environments via divergent natural selection. In central Iberia, two fire salamander subspecies occur in parapatry across elevation gradients along the Iberian Central System mountains, while in the adjacent Montes de Toledo Region only one of them occurs. By integrating population and landscape genetic analyses, we show a ubiquitous role of physical isolation between and within mountain ranges, with unsuitable landscapes increasing differentiation between populations. However, across the Iberian Central System, we found strong support for a significant contribution of ecological isolation, with low genetic differentiation in environmentally homogeneous areas, but high differentiation across sharp transitions in precipitation seasonality. These patterns are consistent with a significant contribution of ecological isolation in restricting gene flow among subspecies. Overall, our results suggest that ecological divergence contributes to reduce genetic admixture, creating an opportunity for lineages to follow distinct evolutionary trajectories.

Sociodemographic factors associated with COVID-19 in-hospital mortality in Brazil.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has highlighted inequalities in access to healthcare systems, increasing racial disparities and worsening health outcomes in these populations. This study analysed the association between sociodemographic characteristics and COVID-19 in-hospital mortality in Brazil. STUDY DESIGN: A retrospective analysis was conducted on quantitative reverse transcription polymerase chain reaction-confirmed hospitalised adult patients with COVID-19 with a defined outcome (i.e. hospital discharge or death) in Brazil. Data were retrieved from the national surveillance system database (SIVEP-Gripe) between February 16 and August 8, 2020. METHODS: Clinical characteristics, sociodemographic variables, use of hospital resources and outcomes of hospitalised adult patients with COVID-19, stratified by self-reported race, were investigated. The primary outcome was in-hospital mortality. The association between self-reported race and in-hospital mortality, after adjusting for clinical characteristics and comorbidities, was evaluated using a logistic regression model. RESULTS: During the study period, Brazil had 3,018,397 confirmed COVID-19 cases and 100,648 deaths. The study population included 228,196 COVID-19-positive adult in-hospital patients with a defined outcome; the median age was 61 years, 57% were men, 35% (79,914) self-reported as Black/Brown and 35.4% (80,853) self-reported as White. The total in-hospital mortality was 37% (85,171/228,196). Black/Brown patients showed higher in-hospital mortality than White patients (42% vs 37%, respectively), were admitted less frequently to the intensive care unit (ICU) (32% vs 36%, respectively) and used more invasive mechanical ventilation (21% vs 19%, respectively), especially outside the ICU (17% vs 11%, respectively). Black/Brown race was independently associated with high in-hospital mortality after adjusting for sex, age, level of education, region of residence and comorbidities (odds ratio = 1.15; 95% confidence interval = 1.09-1.22). CONCLUSIONS: Among hospitalised Brazilian adults with COVID-19, Black/Brown patients showed higher in-hospital mortality, less frequently used hospital resources and had potentially more severe conditions than White patients. Racial disparities in health outcomes and access to health care highlight the need to actively implement strategies to reduce inequities caused by the wider health determinants, ultimately leading to a sustainable change in the health system.

Limited evidence for genetic differentiation or adaptation in two amphibian species across replicated rural-urban gradients.

Urbanization leads to complex environmental changes and poses multiple challenges to organisms. Amphibians are highly susceptible to the effects of urbanization, with land use conversion, habitat destruction, and degradation ranked as the most significant threats. Consequently, amphibians are declining in urban areas, in both population numbers and abundance, however, the effect of urbanization on population genetic parameters remains unclear. Here, we studied the genomic response to urbanization in two widespread European species, the common toad Bufo bufo (26 localities, 480 individuals), and the smooth newt Lissotriton vulgaris (30 localities, 516 individuals) in three geographic regions: southern and northern Poland and southern Norway. We assessed genome-wide SNP variation using RADseq (ca. 42 and 552 thousand SNPs in toads and newts, respectively) and adaptively relevant major histocompatibility complex (MHC) class I and II genes. The results linked most of the genetic differentiation in both marker types to regional (latitudinal) effects, which also correspond to historical biogeography. Further, we did not find any association between genetic differentiation and level of urbanization at local scales for either species. However, urban smooth newts, but not toads, have lower levels of within-population genome-wide diversity, suggesting higher susceptibility to the negative effects of urbanization. A decreasing level of genetic diversity linked to increasing urbanization was also found for MHC II in smooth newts, while the relationship between MHC class I diversity and urbanization differed between geographic regions. We did not find any effects of urbanization on MHC diversity in the toad populations. Although two genetic environment association analyses of genome-wide data, LFMM and BayPass, revealed numerous (219 in B. bufo and 7040 in L. vulgaris) SNPs statistically associated with urbanization, we found a marked lack of repeatability between geographic regions, suggesting a complex and multifaceted response to natural selection elicited by life in the city.

The genomic response to urbanization in the damselfly Ischnura elegans.

The complex and rapid environmental changes brought about by urbanization pose significant challenges to organisms. The multifaceted effects of urbanization often make it difficult to define and pinpoint the very nature of adaptive urban phenotypes. In such situations, scanning genomes for regions differentiated between urban and non-urban populations may be an attractive approach. Here, we investigated the genomic signatures of adaptation to urbanization in the damselfly Ischnura elegans sampled from 31 rural and urban localities in three geographic regions: southern and northern Poland, and southern Sweden. Genome-wide variation was assessed using more than 370,000 single nucleotide polymorphisms (SNPs) genotyped by ddRADseq. Associations between SNPs and the level of urbanization were tested using two genetic environment association methods: Latent Factors Mixed Models and BayPass. While we found numerous candidate SNPs and a highly significant overlap between candidates identified by the two methods within the geographic regions, there was a distinctive lack of repeatability between the geographic regions both at the level of individual SNPs and of genomic regions. However, we found "synapse organization" at the top of the functional categories enriched among the genes located in the proximity of the candidate urbanization SNPs. Interestingly, the overall significance of "synapse organization" was built up by the accretion of different genes associated with candidate SNPs in different geographic regions. This finding is consistent with the highly polygenic nature of adaptation, where the response may be achieved through a subtle adjustment of allele frequencies in different genes that contribute to adaptive phenotypes. Taken together, our results point to a polygenic adaptive response in the nervous system, specifically implicating genes involved in synapse organization, which mirrors the findings from several genomic and behavioral studies of adaptation to urbanization in other taxa.

Preferences for place of death if faced with advanced cancer: a population survey in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain.

BACKGROUND: Cancer end-of-life care (EoLC) policies assume people want to die at home. We aimed to examine variations in preferences for place of death cross-nationally. METHODS: A telephone survey of a random sample of individuals aged ≥16 in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain. We determined where people would prefer to die if they had a serious illness such as advanced cancer, facilitating circumstances, personal values and experiences of illness, death and dying. RESULTS: Of 9344 participants, between 51% (95% CI: 48% to 54%) in Portugal and 84% (95% CI: 82% to 86%) in the Netherlands would prefer to die at home. Cross-national analysis found there to be an influence of circumstances and values but not of experiences of illness, death and dying. Four factors were associated with a preference for home death in more than one country: younger age up to 70+ (Germany, the Netherlands, Portugal, Spain), increased importance of dying in the preferred place (England, Germany, Portugal, Spain), prioritizing keeping a positive attitude (Germany, Spain) and wanting to involve family in decisions if incapable (Flanders, Portugal). CONCLUSIONS: At least two-thirds of people prefer a home death in all but one country studied. The strong association with personal values suggests keeping home care at the heart of cancer EoLC.

The Molecular Effects of BDNF Synthesis on Skeletal Muscle: A Mini-Review.

The brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family which is generated mainly by the brain. Its main role involve synaptic modulation, neurogenesis, neuron survival, immune regulation, myocardial contraction, and angiogenesis in the brain. Together with the encephalon, some peripheral tissues synthesize BDNF like skeletal muscle. On this tissue, this neurotrophin participates on cellular mechanisms related to muscle function maintenance and plasticity as reported on recent scientific works. Moreover, during exercise stimuli the BDNF contributes directly to strengthening neuromuscular junctions, muscle regeneration, insulin-regulated glucose uptake and ß-oxidation processes in muscle tissue. Given its vital relevance on many physiological mechanisms, the current mini-review focuses on discussing up-to-date knowledge about BDNF production in skeletal muscle and how this neurotrophin impacts skeletal muscle biology.

Exercise intensity and physical fitness modulate lipoproteins profile during acute aerobic exercise session.

Physical inactivity has emerged as an important cardiometabolic risk factor; however, the beneficial impacts of physical exercise according physical fitness status are still unclear. To analyze the lipoproteins and immune-endocrine response to acute aerobic exercise sessions performed at different intensities according physical fitness status and evaluated the gene expression in monocyte cells. Twelve individuals, divided into Low and High VO2max, performed three randomized acute exercise sessions at low (<60% VO2max), moderate (60-75% VO2max), and high (>90% VO2max) intensities. Blood samples were collected pre, immediately post, and 60 minutes post-exercise to analyze NEFA, triacylglycerol, non-HDL-c, HDL-c, PAI-1, leptin and adiponectin concentrations. Blood samples were collected from another set of twelve individuals for use in monocyte cell cultures to analyze L-CAT, CETP, and AMPK gene expressions. Low VO2max group pre-exercise exhibited higher postprandial leptin and total cholesterol concentrations than High VO2max group (p < 0.05). Exercise performed in high-intensity promoted a decreased leptin and NEFA levels (p < 0.05, for both), but for PAI-1 levels was decreased (p < 0.05) only for the Low VO2max group. Triacylglycerol levels decreased after all exercise sessions (p < 0.05) for both groups, and HDL-c exhibited decrease during moderate-intensity (p < 0.05), but this scenario was attenuated in Low VO2max group. Low VO2max individuals exhibit some metabolic-endocrine disruption, and acute aerobic exercise sessions performed at low, moderate, and high intensities are capable of modulating metabolic-endocrine parameters, mainly at high-intensity, in a physical fitness-dependent way, given that Low VO2max group was more responsive and seem to be able to appropriate more exercise-related benefits.

Impact of 5-week high-intensity interval training on indices of cardio metabolic health in men.

PURPOSE: To compare the acute and chronic effects of high-intensity intermittent training (HIIT) and moderate-intensity continuous training (MICT) on indices of cardio-metabolic health: (HDL-c, total cholesterol, triglycerides, heart ratio, and phase angle/PhA) in physically active men. METHODS: Twenty active men were randomly allocated to HIIT (n = 10), or MICT (n = 10) for 5 weeks, three times per week. HIIT consisted of running 5 km with 1-min at 100% of maximal aerobic speed interspersed by 1-min passive recovery while subjects in MICT group ran continuously the same 5 km at 70% of maximal aerobic speed. Blood samples were collected at different moments during the first and last exercise session. Before and after 5 weeks of both exercise training protocols, heart ratio (during exercise session) and PhA were measured pre and post-exercise training. RESULTS: Fasting HDL-c levels did not change after 5 weeks of HIIT or MICT. Perceptual variation of HDL pre and post training (fed state) tended to differ between HIIT and MICT (p = 0.09). All lipoproteins parameters (HDL-c, total cholesterol, triglycerides and non-HDL) were increased in post-acute exercise session compared to pre-exercise during the first and last training session, these being observed after both training protocols. PhA and heart rate measured at different times during the first and last training session were not affected in both training protocols. CONCLUSION: These results indicate that HIIT and MICT modify the post-exercise lipoprotein profile acutely. On the other hand, only HIIT tended to increase HDL-c levels chronically.

Sleep quality and duration are associated with performance in maximal incremental test.

BACKGROUND AND OBJECTIVE: Inadequate sleep patterns may be considered a trigger to development of several metabolic diseases. Additionally, sleep deprivation and poor sleep quality can negatively impact performance in exercise training. However, the impact of sleep duration and sleep quality on performance during incremental maximal test performed by healthy men is unclear. Therefore, the purpose of the study was to analyze the association between sleep pattern (duration and quality) and performance during maximal incremental test in healthy male individuals. METHODS: A total of 28 healthy males volunteered to take part in the study. Sleep quality, sleep duration and physical activity were subjectively assessed by questionnaires. Sleep pattern was classified by sleep duration (>7h or <7h of sleep per night) and sleep quality according to the sum of measured points and/or scores by the Pittsburgh Sleep Quality Index (PSQI). Incremental exercise test was performed at 35 watts for untrained subjects, 70 watts for physically active subjects and 105 watts for well-trained subjects. RESULTS: HRmax was correlated with sleep quality (r=0.411, p=0.030) and sleep duration (r=-0.430, p=0.022). Participants reporting good sleep quality presented higher values of Wmax, VO2max and lower values of HRmax when compared to participants with altered sleep. Regarding sleep duration, only Wmax was influenced by the amount of sleeping hours per night and this association remained significant even after adjustment by VO2max. CONCLUSION: Sleep duration and quality are associated, at least in part, with performance during maximal incremental test among healthy men, with losses in Wmax and HRmax. In addition, our results suggest that the relationship between sleep patterns and performance, mainly in Wmax, is independent of fitness condition.

Arterial Thickness and Immunometabolism: The Mediating role of Chronic Exercise.

Metabolic alterations and cardiovascular diseases, such as atherosclerosis, are associated with lifestyle modifications, particularly the increase of physical inactivity and poor eating habits, which contribute to one of the main causes of death in modern times. Cardiovascular diseases are positively correlated with several illnesses, such as obesity, hypertension and dyslipidemia, and these disorders are known to contribute to changes in immune cells, cytokines and metabolism. Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid plaques and fibrous tissue (atheroma) in the artery walls and this process is related to the oxidation of LDL-c (low density lipoprotein) and the formation of a particle, termed LDLox, which can generate toxic injury to the vessel wall. In this atherogenic process there is an inflammatory response generated by the injury in the vascular endothelium, which in itself is able to express and secrete a variety of molecules, such as myeloid colony-stimulating factors (M-CSF), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor alpha (TNF-α), that act as activators of the immune system. Therefore, the main purpose of this review is to highlight the immuno-metabolic alterations involving the thickening and stiffness of arteries observed in atherosclerosis, and how chronic exercise can act as an anti-inflammatory and anti-atherogenic approach.

Chitosan/arginine-chitosan polymer blends for assembly of nanofibrous membranes for wound regeneration.

Frequently, skin is subjected to damaging events, such as deep cuts, burns or ulcers, which may compromise the integrity of this organ. To overcome such lesions, different strategies have been employed. Among them, wound dressings aimed to re-establish skin native properties and decreased patient pain have been pursued for a long time. Herein, an electrospun membrane comprised by deacetylated/arginine modified chitosan (CH-A) was produced to be used as a wound dressing. The obtained results showed that the membrane has a highly hydrophilic and porous three-dimensional nanofibrous network similar to that found in human native extracellular matrix. In vitro data indicate that human fibroblasts adhere and proliferate in contact with membranes, thus corroborating their biocompatibility. This nanofiber-based biomaterial also demonstrated bactericidal activity for two bacterial strains. In vivo application of CH-A nanofibers in full thickness wounds resulted in an improved tissue regeneration and faster wound closure, when compared to non-modified membranes. Such findings support the suitability of using this membrane as a wound dressing in a near future.

Surface modification of polyurethane films by plasma and ultraviolet light to improve haemocompatibility for artificial heart valves.

Prosthetic cardiac valves implantation is a common procedure used to treat heart valve diseases. Although there are different prostheses already available in the market (either mechanical or bioprosthetic), their use presents several problems, specifically concerning thrombogenicity and structural failure. Recently, some progresses have been achieved in developing heart valves based on synthetic materials with special emphasis in polymers. Among them, polyurethanes are one of the most commonly used for the production of these devices. Herein, Elastollan(®)1180A50, a thermoplastic polyurethane (TPU), was used to formulate films whose surfaces were modified by grafting 2-hydroxyethylmethacrylate (HEMA) either by ultra-violet (UV) or by plasma treatment. All films were analyzed before and after grafting. X-ray photoelectron spectroscopy (XPS) measurements were used to evaluate TPU surfaces functionalization. HEMA grafting was confirmed by the increase of the hydroxyl (OH) groups' concentration at the surface of the films. Atomic force microscopy (AFM) analysis was done to evaluate the surface topography of the biomaterials. Results showed that the roughness of the surface decreased when HEMA was grafted, especially for plasma treated samples. After grafting the films' hydrophilicity was improved, as well as the polar component of the surface energy, by 15-30%. Hydrophobic recovery studies using milli Q water or PBS were also performed to characterize the stability of the modified surface, showing that the films maintained their surface properties along time. Furthermore, blood-contact tests were performed to evaluate haemolytic and thrombogenic potential. The results obtained for HEMA grafted surfaces, using plasma treatment, confirmed biomaterials biocompatibility and low thrombogenicity. Finally, the cytotoxicity and antibacterial activity of the materials was assessed through in vitro assays for both modified films. The obtained results showed enhanced bactericidal activity, especially for the films modified with plasma.

The relationship between inflammation, dyslipidemia and physical exercise: from the epidemiological to molecular approach.

Dyslipidemia and inflammation are frequently found in some diseases, such as obesity, type 2 diabetes mellitus, and cancer cachexia. Recent literature has identified that lipids have a pivotal role in the activation of inflammatory pathways, increasing the production of inflammatory cytokines, mainly tumor necrosis factor alpha, interleukin 6 and 1ß. On the other hand, cytokines can promote disruption of lipid metabolism, in special cholesterol reverse transport, which is linked to development of atherosclerosis. With this in mind, acute and chronic exercise trainings have been pointed as important tools to counteract both dyslipidemia symptoms and systemic inflammation. Moreover, physical activity has been recommended in the prevention/treatment of the above mentioned outcomes by important health organizations around the world, mainly because it costs less and generates fewer side effects than isolated medicine. Despite the well-documented capacity of acute and chronic exercise training to counteract sustained disease-related immunometabolism, we have chosen to take a look from a current perspective in molecular pathways and in the field of epidemiology. The aim of the present review was therefore to discuss the results of dyslipidemia and inflammatory conditions with acute and chronic exercise training, which underlies the field of molecular pathways and epidemiology. The mechanisms underlying the response to the treatment are considered.