Exogenous ghrelin attenuates endotoxin fever in rats

AbstractGhrelin is a gut-derived peptide that plays a role in energy homeostasis. Recent studies have implicated ghrelin in systemic inflammation, showing increased plasma ghrelin levels after endotoxin (lipopolysaccharide, LPS) administration. The aims of this study were (1) to test the hypothesis that ghrelin administration affects LPS-induced fever; and (2) to assess the putative effects of ghrelin on plasma corticosterone secretion and preoptic region prostaglandin (PG) E2 levels in euthermic and febrile rats. Rats were implanted with a temperature datalogger capsule in the peritoneal cavity to record body core temperature. One week later, they were challenged with LPS (50μg/kg, intraperitoneal, i.p.) alone or combined with ghrelin (0.1mg/kg, i.p.). In another group of rats, plasma corticosterone and preoptic region PGE2 levels were measured 2h after injections. In euthermic animals, systemic administration of ghrelin failed to elicit any thermoregulatory effect, and caused no significant changes in basal plasma corticosterone and preoptic region PGE2 levels. LPS caused a typical febrile response, accompanied by increased plasma corticosterone and preoptic PGE2 levels. When LPS administration was combined with ghrelin fever was attenuated, corticosterone secretion further increased, and the elevated preoptic PGE2 levels were relatively reduced, but a correlation between these two variables (corticosterone and PGE2) failed to exist. The present data add ghrelin to the neurochemical milieu controlling the immune/thermoregulatory system acting as an antipyretic molecule. Moreover, our findings also support the notion that ghrelin attenuates fever by means of a direct effect of the peptide reducing PGE2 production in the preoptic region

Hydrogen sulfide inhibits preoptic prostaglandin E2 production during endotoxemia

AbstractHydrogen sulfide (H2S) is a gaseous neuromodulator endogenously produced in the brain by the enzyme cystathionine β-synthase (CBS). We tested the hypothesis that H2S acts within the anteroventral preoptic region of the hypothalamus (AVPO) modulating the production of prostaglandin (PG) E2 (the proximal mediator of fever) and cyclic AMP (cAMP). To this end, we recorded deep body temperature (Tb) of rats before and after pharmacological modulation of the CBS–H2S system combined or not with lipopolysaccharide (LPS) exposure, and measured the levels of H2S, cAMP, and PGE2 in the AVPO during systemic inflammation. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100pmol) did not affect basal PGE2 production and Tb, but enhanced LPS-induced PGE2 production and fever, indicating that endogenous H2S plays an antipyretic role. In agreement, icv microinjection of a H2S donor (Na2S; 260nmol) reduced the LPS-induced PGE2 production and fever. Interestingly, we observed that the AVPO levels of H2S were decreased following the immunoinflammatory challenge. Furthermore, fever was associated with decreased levels of AVPO cAMP and increased levels of AVPO PGE2. The LPS-induced decreased levels of cAMP were reduced to a lesser extent by the H2S donor. The LPS-induced PGE2 production was potentiated by AOA (the CBS inhibitor) and inhibited by the H2S donor. Our data are consistent with the notion that the gaseous messenger H2S synthesis is downregulated during endotoxemia favoring PGE2 synthesis and lowering cAMP levels in the preoptic hypothalamus

The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019

Background: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. Methods: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). Results: In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for “HIV/AIDS and sexually transmitted diseases” and “transport injuries” (each -19%). “Diabetes and kidney diseases” showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, “mental disorders” showed an increasing age-standardised YLL rate (14.5%). Conclusions: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease

The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019

Background: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010.Methods: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE).Results:In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for "HIV/AIDS and sexually transmitted diseases" and "transport injuries" (each -19%). "Diabetes and kidney diseases" showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, "mental disorders" showed an increasing age-standardised YLL rate (14.5%).Conclusions: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Climate changes in mangrove forests and salt marshes

Abstract This synthesis is framed within the scope of the Brazilian Benthic Coastal Habitat Monitoring Network (ReBentos WG 4: Mangroves and Salt Marshes), focusing on papers that examine biodiversity-climate interactions as well as human-induced factors including those that decrease systemic resilience. The goal is to assess difficulties related to the detection of climate and early warning signals from monitoring data. We also explored ways to circumvent some of the obstacles identified. Exposure and sensitivity of mangrove and salt marsh species and ecosystems make them extremely vulnerable to environmental impacts and potential indicators of sea level and climate-driven environmental change. However, the interpretation of shifts in mangroves and salt marsh species and systemic attributes must be scrutinized considering local and setting-level energy signature changes; including disturbance regime and local stressors, since these vary widely on a regional scale. The potential for adaptation and survival in response to climate change depends, in addition to the inherent properties of species, on contextual processes at the local, landscape, and regional levels that support resilience. Regardless of stressor type, because of the convergence of social and ecological processes, coastal zones should be targeted for anticipatory action to reduce risks and to integrate these ecosystems into adaptation strategies. Management must be grounded on proactive mitigation and collaborative action based on long-term ecosystem-based studies and well-designed monitoring programs that can 1) provide real-time early warning and 2) close the gap between simple correlations that provide weak inferences and process-based approaches that can yield increasingly reliable attribution and improved levels of anticipation

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Marine-Derived Biologically Active Compounds for the Potential Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with a prevalence rate of up to 1% and is significantly considered a common worldwide public health concern. Commercially, several traditional formulations are available to treat RA to some extent. However, these synthetic compounds exert toxicity and considerable side effects even at lower therapeutic concentrations. Considering the above-mentioned critiques, research is underway around the world in finding and exploiting potential alternatives. For instance, marine-derived biologically active compounds have gained much interest and are thus being extensively utilized to confront the confines of in practice counterparts, which have become ineffective for 21st-century medical settings. The utilization of naturally available bioactive compounds and their derivatives can minimize these synthetic compounds’ problems to treat RA. Several marine-derived compounds exhibit anti-inflammatory and antioxidant properties and can be effectively used for therapeutic purposes against RA. The results of several studies ensured that the extraction of biologically active compounds from marine sources could provide a new and safe source for drug development against RA. Finally, current challenges, gaps, and future perspectives have been included in this review

Involvement of endogenous central hydrogen sulfide (H2S) in hypoxia-induced hypothermia in spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) display autonomic imbalance and abnormal body temperature (Tb) adjustments. Hydrogen sulfide (H2S) modulates hypoxia-induced hypothermia but its role in SHR thermoregulation is unknown. We tested the hypothesis that SHR display peculiar thermoregulatory response to hypoxia, and that endogenous H2S overproduced in the caudal nucleus of the solitary tract (NTS) of SHR modulates this response. SHR and Wistar rats were microinjected into the fourth ventricle with aminooxyacetate (AOA, H2S-synthesing enzyme inhibitor) or sodium sulfide (Na2S, H2S donor) and exposed to normoxia (21% inspired O2) or hypoxia (10% inspired O2, 30 min). Tb was continuously measured, and H2S production rate was assessed in caudal NTS homogenates. In both groups, AOA, Na2S or vehicle (saline, 1 ÂľL) did not affect euthermia. Hypoxia caused similar decreases in Tb in both groups. AOA presented a longer latency to potentiate hypoxic hypothermia in SHR. Caudal NTS H2S production rate was higher in SHR. We suggest that increased bioavailability of H2S in the caudal NTS of SHR enables the adequate modulation of excitability of peripheral chemoreceptors-activated NTS neurons that ultimately induce suppression of brown adipose tissue thermogenesis thus accounting for the normal hypoxic hypothermia.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author