Bench-to-bedside review: The role of glycosaminoglycans in respiratory disease.

The extracellular matrix (ECM) plays a significant role in the mechanical behaviour of the lung parenchyma. The ECM is composed of a three-dimensional fibre mesh that is filled with various macromolecules, among which are the glycosaminoglycans (GAGs). GAGs are long, linear and highly charged heterogeneous polysaccharides that are composed of a variable number of repeating disaccharide units. There are two main types of GAGs: nonsulphated GAG (hyaluronic acid) and sulphated GAGs (heparan sulphate and heparin, chondroitin sulphate, dermatan sulphate, and keratan sulphate). With the exception of hyaluronic acid, GAGs are usually covalently attached to a protein core, forming an overall structure that is referred to as proteoglycan. In the lungs, GAGs are distributed in the interstitium, in the sub-epithelial tissue and bronchial walls, and in airway secretions. GAGs have important functions in lung ECM: they regulate hydration and water homeostasis; they maintain structure and function; they modulate the inflammatory response; and they influence tissue repair and remodelling. Given the great diversity of GAG structures and the evidence that GAGs may have a protective effect against injury in various respiratory diseases, an understanding of changes in GAG expression that occur in disease may lead to opportunities to develop innovative and selective therapies in the future

Galectin-3-null mice display defective neutrophil clearance during acute inflammation

Galectin-3 has been associated with a plethora of proinflammatory functions because of its ability, among others, to promote neutrophil activation and because of the reduction in neutrophil recruitment in models of infection in Gal-3-null mice. Conversely, it has also been linked to resolution of inflammation through its actions as an opsonin and its ability to promote efferocytosis of apoptotic neutrophils. Using a self-resolving model of peritonitis, we have addressed the modulation and role of Gal-3 in acute inflammation. We have shown that Gal-3 expression is increased in neutrophils that travel to the inflamed peritoneum and that cellular localization of this lectin is modulated during the course of the inflammatory response. Furthermore, neutrophil recruitment to the inflamed peritoneum is increased in Gal-3–null mice during the course of the response, and that correlates with reduced numbers of monocytes/macrophages in the cavities of those mice, as well as reduced apoptosis and efferocytosis of Gal-3–null neutrophils. These data indicate a role for endogenous Gal-3 in neutrophil clearance during acute inflammation

COVID-19 Mortality and Case-Fatality Rates in Sergipe State, Northeast Brazil, From April to June 2020

Information on how coronavirus disease 2019 (COVID-19) mortality is related to population characteristics in low- and middle-income countries is still limited. We described the deaths from COVID-19 in Sergipe state, Northeast Brazil, from April 2 to June 27, 2020. For this purpose, we conducted a study composed of (i) a case series study of all deaths due to COVID-19 and (ii) a population-based study to verify the behavior of the mortality and case-fatality rates (CFR) related to COVID-19. Data from 605 deaths due to COVID-19 were used to describe the characteristics of individuals with the disease, as well as the differences in gender, age, and comorbidities. Additionally, population data were extracted to estimate the mortality and CFR by population stratum. We also performed an adjusted CFR analysis including a time lag of 14 days between the onset of symptoms and reporting deaths. Of the 605 patients included in this study, 321 (53.1%) were males and the median age was 67.0 years. Most patients (n = 447, 73.9%) who died from COVID-19 had at least one pre-existing clinical condition. The mortality rate was 29.3 deaths per 100,000 inhabitants and the crude CRF was 2.6% (95% CI 2.4–2.8). CFR was higher in males (3.1%, 95% CI 2.8–3.4; p < 0.001) and people aged =60 years (14.2%, 95% CI 13.0–15.6; p = 0.042). About 25% of patients died during the first 24-h post-hospital admission. The adjusted CFR for a 14-day time lag was ~2-fold higher than the crude CFR over the study period.We dedicated this article to all health professionals who are facing COVID-19. This study was part of the EpiSERGIPE project. NM thanks the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/280 76/2017)

Child-OIDP index in Brazil: Cross-cultural adaptation and validation

Background: Oral health-related quality of life (OHRQoL) measures are being increasingly used to introduce dimensions excluded by normative measures. Consequently, there is a need for an index which evaluates children's OHRQoL validated for Brazilian population, useful for oral health needs assessments and for the evaluation of oral health programs, services and technologies. The aim of this study was to do a cross-cultural adaptation of the Child Oral Impacts on Daily Performances (Child-OIDP) index, and assess its reliability and validity for application among Brazilian children between the ages of eleven and fourteen. Methods: For cross-cultural adaptation, a translation/back-translation method integrated with expert panel reviews was applied. A total of 342 students from four public schools took part of the study. Results: Overall, 80.7% of the sample reported at least one oral impact in the last three months. Cronbach's alpha was 0.63, the weighted kappa 0.76, and the intraclass correlation coefficient (ICC) 0.79. The index had a significant association with self-reported health measurements (self-rated oral health, satisfaction with oral health, perceived dental treatment needs, self-rated general health; all p < 0.01). Conclusion: It was concluded that the Child-OIDP index is a measure of oral health-related quality of life that can be applied to Brazilian children

Evaluation of objective and subjective indicators of death in a period of one year in a sample of prevalent patients under regular hemodialysis

<p>Abstract</p> <p>Background</p> <p>To identify objective and subjective indicators of death in prevalent hemodialysis (HD) patients in a follow-up study of 12 months.</p> <p>Methods</p> <p>The study included end-stage renal disease patients undergoing HD and analyzed demographic and laboratory data from the dialysis unit's records. Baseline data concerning socioeconomic status, comorbidity, quality of life level, coping style and depression were also assessed. For variables that differed in the comparison between survivors and non-survivors, Cox proportional hazards for death were calculated.</p> <p>Results</p> <p>The mortality rate was 13.0%. Non-survivors differed in age, comorbidity, inclusion on the transplant waiting list and physical functioning score. The hazard ratios of death were 8.958 (2.843-28.223; <it>p </it>< 0.001) for comorbidity, 3.992 (1.462-10.902; <it>p </it>= 0.007) for not being on the transplant waiting list, 1.038 (1.012-1.066; <it>p </it>= 0.005) for age, and 0.980 (0.964-0.996; <it>p </it>= 0.014) for physical functioning.</p> <p>Conclusions</p> <p>Comorbidity, not being on the transplant waiting list, age and physical functioning, which reflects physical status, must be seen as risk indicators of death among patients undergoing HD.</p

Correlation between the heterosis of maize hybrids and genetic divergence among lines

The objective of this work was to evaluate grain yield of maize single cross hybrids obtained from diallel crosses among contrasting lines, to estimate the combining ability of the lines, and finally to confirm if the genetic diversity among those lines assessed by molecular markers is correlated with single cross hybrids heterosis. The 36 single cross hybrids resulting from partial diallel and 12 parental lines were evaluated in Campinas in randomized block design, with three replicates and two control lines checks. General combining ability of the lines was estimated according to Griffing model 4. Correlations among matrices were estimated through Mantel statistics, considering heterosis, yield and specific combining ability with genetic divergence assessed by AFLP and SSR. The hybrids PM518 x L111 exhibited an outstanding yield and the lines PM518, IP4035 and L111 showed positive general combining ability. The estimate heterosis ranged from 927 to 6,698 kg ha(-1). A positive and significant correlation was observed in parental lines between heterosis and genetic diversity assessed by AFLP and SSR. The genetic divergence, however, was not enough to determine the specific combining ability and the hybrids yield.42681181

Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in Covid-19.

Rationale: Resolution mechanisms are central in both the maintenance of homeostasis and the return to catabasis following tissue injury and/or infections. Amongst the pro-resolving mediators, the essential fatty acid-derived specialized pro-resolving lipid mediators (SPM) govern immune responses to limit disease severity. Notably, little is known about the relationship between the expression and activity of SPM pathways, circulating phagocyte function and disease severity in patients infected with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to coronavirus disease 2019 (COVID-19). Objective: Herein, we investigated the link between circulating SPM concentrations and phagocyte activation status and function in COVID-19 patients (n=39) compared to healthy (n=12) and post-COVID-19 (n=8) volunteers. Methods and Results: Lipid mediator profiling demonstrated that plasma SPM concentrations were upregulated in patients with mild COVID-19 and are downregulated in those with severe disease. SPM concentrations were correlated with both circulating phagocyte activation status and function. Perturbations in plasma SPM concentrations and phagocyte activation were retained after the resolution of COVID-19 clinical symptoms. Treatment of patients with dexamethasone upregulated both the expression of SPM biosynthetic enzymes in circulating phagocytes and plasma concentration of these mediators. Furthermore, incubation of phagocytes from COVID-19 patients with SPM rectified their phenotype and function. This included a downregulation in the expression of activation markers, a decrease in the Tissue Factor and inflammatory cytokine expression, and an upregulation of bacterial phagocytosis. Conclusions: The present findings suggest that downregulation of systemic SPM concentrations is linked with both increased disease severity and dysregulated phagocyte function. They also identify the upregulation of these mediators by dexamethasone as a potential mechanism in host protective activities elicited by this drug in COVID-19 patients. Taken together, our findings elucidate a role for altered resolution mechanisms in the disruption of phagocyte responses and the propagation of systemic inflammation in COVID-19