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Background: Patients with Coronavirus Disease 2019 (COVID-19) may present high risk features during hospitalization, including cardiovascular manifestations. However, less is known about the factors that may further increase the risk of death in these patients. Methods: We included patients with COVID-19 and high risk features according to clinical and/or laboratory criteria at 21 sites in Brazil from June 10th to October 23rd of 2020. All variables were collected until hospital discharge or in-hospital death. Results: A total of 2546 participants were included (mean age 65 years; 60.3% male). Overall, 70.8% were admitted to intensive care units and 54.2% had elevated troponin levels. In-hospital mortality was 41.7%. An interaction among sex, age and mortality was found (p = 0.007). Younger women presented higher rates of death than men (30.0% vs 22.9%), while older men presented higher rates of death than women (57.6% vs 49.2%). The strongest factors associated with in-hospital mortality were need for mechanical ventilation (odds ratio [OR] 8.2, 95% confidence interval [CI] 5.4–12.7), elevated C-reactive protein (OR 2.3, 95% CI 1.7–2.9), cancer (OR 1.8, 95 %CI 1.2–2.9), and elevated troponin levels (OR 1.8, 95% CI 1.4–2.3). A risk score was developed for risk assessment of in-hospital mortality. Conclusions: This cohort showed that patients with COVID-19 and high risk features have an elevated rate of in-hospital mortality with differences according to age and sex. These results highlight unique aspects of this population and might help identifying patients who may benefit from more careful initial surveillance and potential subsequent interventional therapies.

It is well established that diets containing an increased omega-6 polyunsaturated fatty acid (n-6 PUFA) to omega-3 polyunsaturated fatty acid (n-3 PUFA) ratios are linked to inflammation and chronic diseases such as nonalcoholic fatty liver disease (NAFLD). However, the influence of an elevated n-6 PUFA:n-3 PUFA ratio in the tissues requires clarification. Herein, we identified primary experimental and clinical studies where it is possible to compare the performance of the myristic acid (Myr):docosahexaenoic acid (DHA) and n-6 PUFA:n-3 PUFA ratios in the liver and/or serum as potential NAFLD biomarkers. Articles were included if quantitative values of n-6 PUFA, n-3 PUFA, Myr, DHA, and information about liver inflammation or liver disease progression parameters were provided. Overall, most experimental (91.6%) and clinical studies (87.5%) reported higher Myr:DHA ratios associated with inflammation and/or NAFLD progression than the n-6 PUFA:n-3 PUFA ratio. We conclude that the Myr:DHA ratio represents a better biomarker of NAFLD than the n-6 PUFA:n-3 PUFA ratio. Future studies are necessary for verifying this observation.

Background: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil., Methods: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period., Results: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSβ 0 -thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSβ 0 -thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSβ 0 -thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use., Discussion: In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSβ 0 -thalassemia but is dependent on adherence level., (© 2022. The Author(s).)

We previously reported that a high-carbohydrate diet (HCD) induced systemic inflammation and higher gene expression of proinflammatory mediators in the liver, skeletal muscle, and brain than a high-fat diet (HFD). However, the differences between the groups were less pronounced in the brain. In this study, we extended the evaluation of inflammation to specific areas of the brain. In this study, we evaluated the gene expression of caspase 2, caspase 3, caspase 9 , cyclooxygenase-2 ( Cox 2 ), inducible nitric oxide synthase ( iNOS ), interleukin (IL), IL-6, IL-1β, IL-10, IL-4 , tumor necrosis factor-alpha ( TNF-α ), integrin subunit alpha m ( Itgam ), S100 protein ( S100 ), allograft inflammatory factor 1 ( Aif1 ), and glial fibrillary acidic protein ( Gfap ) in the prefrontal cortex and hippocampus of male Swiss mice that were fed with HCD or HFD for 8 weeks. The HCD group exhibited higher IL-1β expression, whereas the HFD group showed higher TNF-α expression in the prefrontal cortex. In the hippocampus, TNF-α expression was higher in the HFD group. IL-1 β and TNF- α are proinflammatory cytokines that have been associated with impaired brain function and numerous brain disorders. Our results indicate that both HCD and HFD promote prefrontal cortex inflammation; however, the hippocampus seems more sensitive to a HFD than HCD.

We compared the effect of oral glucose versus oral glucose combined with glycerol (glucose + glycerol) in promoting glucose recovery during hypoglycemia. These studies were carried out in two series of experiments. In the first series of experiments, 16 overnight fasted rats received an intraperitoneal injection of lispro insulin (1 IU/kg), and 25 min later, they received oral water (control), glucose (0.25 g/kg), glycerol (2.5 g/kg), or glucose (0.25 g/kg) + glycerol (2.5 g/kg). In the second series of experiments on 164 eligible type 1 diabetic (T1D) patients, 30 individuals with a history of hypoglycemia were recruited. Five volunteers did not meet the inclusion criteria and two subjects were excluded after starting the clinical investigation; 23 patients concluded the study. All patients with symptoms of hypoglycemia ingested oral glucose (15 g) or glucose (15 g) + glycerol (9.45 g). To treat hypoglycemia in T1D patients, preparations containing glucose alone or glucose + glycerol were used alternately (2 weeks/2 weeks) in a double-blind crossover scheme. Throughout the clinical research (4 weeks), glucose concentrations were assessed with a continuous glucose monitoring device and the results after the use of glucose alone or glucose + glycerol preparations were compared. Oral glucose combined with glycerol was more effective in promoting glucose recovery in comparison with glucose alone, not only in rats but also in T1D patients. Taken together, our experimental and clinical investigations reported the best performance of oral administration of glucose + glycerol in comparison with isolated glucose.

The study aimed to measure serum fatty acids (FAs) composition in HIV carrier patients and compare it with non-HIV carrier patients. The FAs composition was measured by gas chromatography as follows: four saturated FAs myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0), and docosanoic acid (22:0); four monounsaturated FAs 7-hexadecenoic acid (16:1 n-9), palmitoleic acid (16:1 n-7), oleic acid (18:1 n-9), and vaccenic acid (18:1 n-7); and three polyunsaturated FAs linoleic acid (18:2 n-6), dihomo- γ -linolenic acid (20:3 n-6), and docosahexaenoic acid (DHA, 22:6 n-3). We reported herein lower ( P  < .05) DHA concentration (by 40%) in the serum of HIV carrier patients than in non-HIV carrier patients. This FA has a pivotal role as a precursor of anti-inflammatory molecules with beneficial effects on metabolism, cardiovascular system, and immunological system. Even though most clinical studies reported beneficial effects of DHA supplementation in HIV carrier patients, this issue remains under debate. Further investigations then require to fully clarify the role of DHA in preventing or alleviating the comorbidities associated with HIV infection.

Cancer-bearing often exhibits hypoinsulinemia, insulin (INS) resistance and glutamine depletion associated with cachexia. However, INS and glutamine effects on cachexia metabolic abnormalities, particularly on tumor-affected proteins related to INS resistance, are poorly known. The main purpose of this study was to investigate the effects of INS and glutamine dipeptide (GDP) treatments on phospho-protein kinase B (p-Akt), and phospho-hormone sensitive lipase (p-HSL) in Walker-256 tumor-bearing rats. INS (NPH, 40 UI/kg, subcutaneous), GDP (1.5 g/kg, oral), INS+GDP or vehicle (control rats) were administered for 13 days, once a day, starting at the day of inoculation of tumor cells. The experiments were performed 4 hours after the last treatment to evaluate acute effects of INS and GDP, besides the chronic effects. INS and/or INS+GDP treatments, which markedly increased the insulinemia, increased the p-Akt: total Akt ratio and prevented the increased p-HSL Ser552 : total HSL ratio in the retroperitoneal fat of tumor-bearing rats, without changing the INS resistance and increased expression of factor tumor necrosis-α (TNF-α) in this tissue. INS and INS+GDP also increased the p-Akt: total Akt ratio, whereas GDP and INS+GDP increased the GLUT4 glucose transporter gene expression, in the gastrocnemius muscle of the tumor-bearing rats. Accordingly, treatments with INS and INS+GDP markedly reduced glycemia, increased retroperitoneal fat and attenuated the body mass loss of tumor-bearing rats. In conclusion, hyperinsulinemia induced by high-dose INS treatments increased Akt phosphorylation and prevented increased p-HSL Ser552 : total HSL ratio, overlapping INS resistance. These effects are consistent with increased fat mass gain and weight loss (cachexia) attenuation of tumor-bearing rats, evidencing that Akt activation is a potential strategy to prevent loss of fat mass in cancer cachexia., (© 2020 Wiley Periodicals, Inc.)

Both high fat diet (HFD) and high carbohydrate diet (HCD) modulate brain fatty acids (FA) composition. Notwithstanding, there is a lack of information on time sequence of brain FA deposition either for HFD or HCD. The changes in brain FA composition in mice fed with HFD or HCD for 7, 14, 28, or 56 days were compared with results of 0 (before starting given the diets). mRNA expressions of allograft inflammatory factor 1 (Aif1), cyclooxygenase-2 (Cox 2), F4/80, inducible nitric oxide synthase (iNOS), integrin subunit alpha m (Itgam), interleukin IL-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor alpha (TNF-α) were measured. The HFD group had higher speed of deposition of saturated FA (SFA), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA) at the beginning of the experimental period. However, on day 56, the total amount of SFA, MUFA, and PUFA were similar. mRNA expressions of F4/80 and Itgam, markers of microglia infiltration, were increased ( p < 0.05) in the brain of the HCD group whereas inflammatory marker index (IMI) was higher (46%) in HFD group. In conclusion, the proportion of fat and carbohydrates in the diet modulates the speed deposition of FA and expression of inflammatory gene markers.

In this combined experimental-theoretical work we focus on the physical and chemical changes induced by soft X-rays on sulfur dioxide (SO 2 ) ice at a very low temperature, in an attempt to clarify and quantify its survival and chemical changes in some astrophysical environments. SO 2 is an important constituent of some Jupiter moons and has also been observed in ices around protostars. The measurements were performed at the Brazilian Synchrotron Light Source (LNLS/CNPEM), in Campinas, Brazil. The SO 2 ice sample (12 K) was exposed to a broadband beam of mainly soft X-rays (6-2000 eV) and in situ analyses were performed by IR spectroscopy. The X-ray photodesorption yield (upper limit) was around 0.25 molecules per photon. The values determined for the effective destruction (SO 2 ) and formation (SO 3 ) cross sections were 2.5 × 10 -18 cm 2 and 2.1 × 10 -18 cm 2 , respectively. The chemical equilibrium (88% of SO 2 and 12% of SO 3 ) was reached after the fluence of 1.6 × 10 18 photons cm -2 . The SO 3 formation channels were studied at the second-order Møller-Plesset perturbation theory (MP2) level, which showed the three most favorable reaction routes (ΔH < -79 kcal mol -1 ) in simulated SO 2 ice: (i) SO + O 2 → SO 3 , (ii) SO 2 + O → SO 3 , and (iii) SO 2 + O + → SO 3 + + e - → SO 3 . The amorphous solid environment effect decreases the reactivity of intermediate species towards SO 3 formation, and ionic species are even more affected. The experimentally determined effective cross sections and theoretical reaction channels identified in this work allow us to better understand the chemical evolution of certain sulfur-rich astrophysical environments.

The diversity of MSP1 in both Plasmodium falciparum and P. vivax is presumed be associated to parasite immune evasion. In this study, we assessed genetic diversity of the most variable domain of vaccine candidate N-terminal PvMSP1 (Block 2) in field isolates of Manaus. Forty-seven blood samples the polymorphism of PvMSP1 Block 2 generates four fragment sizes. In twenty-eight of them, sequencing indicated seven haplotypes of PvMSP1 Block 2 circulating among field isolates. Evidence of striking exchanges was observed with two stretches flanking the repeat region and two predicted recombination sites were described. Single nucleotide polymorphisms determined with concurrent infections per patient indicated that nonsynonymous substitutions occurred preferentially in the repeat-rich regions which also were predicted as B-cell epitopes. The comprehensive understanding of the genetic diversity of the promising Block 2 associated with clinical immunity and a reduced risk of infection by Plasmodium vivax would be important for the rationale of malaria vaccine designs.

The lipoxygenase isoenzymes LOX1 and LOX2 from green malt were separated by isoelectric focusing, and their catalytic properties regarding complex lipids as substrates were characterized. The regio- and stereoisomers of hydroperoxy octadecadienoates (HPODE) resulting from LOX1 and LOX2 enzymatic transformations of linoleic acid, methyl linoleate, linoleic acid glycerol esters monolinolein, dilinolein, and trilinolein, and 1-palmitoyl-2-linoleoyl-glycero-3-phosphocholine (PamLinGroPCho) were determined. In addition, biotransformations of polar and nonpolar lipids extracted from malt were performed with LOX1 and LOX2. The results show that LOX2 catalyzes the oxidation of esterified fatty acids at a higher rate and is more regioselective than LOX1. The dual position specificity of LOX2 (9-HPODE:13-HPODE) with trilinolein as the substrate (6:94) was higher than the resultant ratio (13:87) when free linoleic acid was transformed. A high (S)-enantiomeric excess of 13-HPODE was analyzed with all esterified substrates confirming the formation of 13-HPODE through the LOX2 enzyme; however, 9-HPODE detected after LOX2 biotransformations showed (R)-enantiomeric excesses. PamLinGroPCho was oxygenated by LOX1 with the highest regio- and stereoselectivities among the applied substrates.