Trehalose Improved 20-min Cycling Time-Trial Performance After 100-min Cycling in Amateur Cyclists.

Carbohydrate (CHO) supplementation during endurance exercise can improve performance. However, it is unclear whether low glycemic index (GI) CHO leads to differential ergogenic and metabolic effects compared with a standard high GI CHO. This study investigated the ergogenic and metabolic effects of CHO supplementation with distinct GIs, namely, (a) trehalose (30 g/hr), (b) isomaltulose (30 g/hr), (c) maltodextrin (60 g/hr), and (d) placebo (water). In this double-blind, crossover, counterbalanced, placebo-controlled study, 13 male cyclists cycled a total of 100 min at varied exercise intensity (i.e., 10-min stages at 1.5, 2.0, and 2.5 W/kg; repeated three times plus two 5-min stages at 1.0 W/kg before and after the protocol), followed by a 20-min time trial on four separated occasions. Blood glucose and lactate (every 20 min), heart rate, and ratings of perceived exertion were collected throughout, and muscle biopsies were taken before and immediately after exercise. The results showed that trehalose improved time-trial performance compared with placebo (total work done 302 ± 39 vs. 287 ± 48 kJ; p = .01), with no other differences between sessions (all p ≥ .07). Throughout the 100-min protocol, blood glucose was higher with maltodextrin compared with the other supplements at all time points (all p < .05). Heart rate, ratings of perceived exertion, muscle glycogen content, blood glucose, and lactate were not different between conditions when considering the 20-min time trial (all p > .05). Trehalose supplementation throughout endurance exercise improved cycling performance and appears to be an appropriate CHO source for exercise tasks up to 2 hr. No ergogenic superiority between the different types of CHO was established.

Does acute exposure to thimerosal, an organic mercury compound, affect the mitochondrial function of an infant model?

BACKGROUND: Thimerosal (TM) is a toxic, organometallic mercury compound (which releases ethyl-mercury-containing compounds in aqueous solutions) used as a preservative in vaccines. Mitochondria are organelle which are highly vulnerable to many chemical compounds, including mercury (Hg) and its derivatives. METHOD: Wistar rats (at 21 days of age) were used to model a child's TM exposure following childhood vaccination, divided in two groups: TM exposed (20 µg/kg/day) and unexposed controls (saline solution), both for 24 h. Atomic Fluorescence Spectrometry was used to quantify the amounts of mercury in tissues. The electron transport chain (ETC) from isolated mitochondria was evaluated using an oxygen electrode. The mitochondrial membrane potential and H2O2 production were analyzed using selective fluorescence probes. The activity of some enzymes (SOD, CAT, GPx, and AChE) and secondary markers of oxidative stress (GSH, GSSG, total free thiol) were also examined in tissues. RESULTS: Hg accumulation in the brain and liver was higher in exposed animals when compared to the control. Liver-isolated mitochondria showed that TM improved respiratory control by 23%; however, states 3 and 4 of the ETC presented a decrease of 16% and 37%, respectively. Furthermore, brain-isolated mitochondria presented an improvement of 61% in respiratory control. Brain enzyme activities were significantly impacted in TM-exposed rats compared to unexposed rats as follows: decreases in SOD (32%) and AChE (42%) and increases in GPx (79%) and CAT (100%). GPx enzyme activity in the liver was significantly increased (37%). Among secondary oxidative stress markers, the brain's total reduced thiol (SH) concentration was significantly increased (41%). CONCLUSION: Acute TM treatment exposure in a Wistar rat model mimicking TM exposure in an infant following childhood vaccination significantly damaged brain bioenergetic pathways. This study supports the ability of TM exposure to preferentially damage the nervous system.

The recombinant L-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells.

BACKGROUND: In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. L-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. L-lysine α-oxidase, a flavoenzyme that degrades L-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of L-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. RESULTS: The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. CONCLUSIONS: The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.

Cardiorespiratory abnormalities in ICU survivors of COVID-19 with postacute sequelae of SARS-CoV-2 infection are unrelated to invasive mechanical ventilation.

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) often leads to exertional intolerance and reduced exercise capacity, particularly in individuals previously admitted to an intensive care unit (ICU). However, the impact of invasive mechanical ventilation (IMV) on PASC-associated cardiorespiratory abnormalities during exercise remains poorly understood. This single-center, cross-sectional study aimed to gather knowledge on this topic. Fifty-two patients with PASC recruited ∼6 mo after ICU discharge were clustered based on their need for IMV (PASC + IMV, n = 27) or noninvasive support therapy (PASC + NIS, n = 25). Patients underwent pulmonary function and cardiopulmonary exercise testing (CPX) and were compared with a reference group (CONTROL, n = 19) comprising individuals of both sexes with similar age, comorbidities, and physical activity levels but without a history of COVID-19 illness. Individuals with PASC, irrespective of support therapy, presented with higher rates of cardiorespiratory abnormalities than CONTROL, especially dysfunctional breathing patterns, dynamic hyperinflation, reduced oxygen uptake and oxygen pulse, and blunted heart rate recovery (all P < 0.05). Only the rate of abnormal oxygen pulse was greater among PASC + IMV group than PASC + NIS group (P = 0.05). Mean estimates for all CPX variables were comparable between PASC + IMV and PASC + NIS groups (all P > 0.05). These findings indicate significant involvement of both central and peripheral factors, leading to exertional intolerance in individuals with PASC previously admitted to the ICU, regardless of their need for IMV.NEW & NOTEWORTHY We found cardiorespiratory abnormalities in ICU survivors of severe-to-critical COVID-19 with PASC to be independent of IMV need. Overall, both group of patients experienced dysfunctional breathing patterns, dynamic hyperinflation, lower oxygen uptake and oxygen pulse, and blunted heart rate responses to CPX. PASC seems to impact exertional tolerance and exercise capacity due to ventilatory inefficiency, impaired aerobic metabolism, and potential systolic and autonomic dysfunction, all of these irrespective of support therapy during ICU stay.

Study of nitrogen heterocycles as DNA/HSA binder, topoisomerase inhibitors and toxicological safety.

Four new nitrogen-containing heterocyclic derivatives (acridine, quinoline, indole, pyridine) were synthesized and their biological properties were evaluated. The compounds showed affinity for DNA and HSA, with CAIC and CAAC displaying higher binding constants (Kb) of 9.54 × 104 and 1.06 × 106, respectively. The fluorescence quenching assay (Ksv) revealed suppression values ranging from 0.34 to 0.64 × 103 M-1 for ethidium bromide (EB) and 0.1 to 0.34 × 103 M-1 for acridine orange (AO). Molecular docking confirmed the competition of the derivatives with intercalation probes at the same binding site. At 10 µM concentrations, the derivatives inhibited topoisomerase IIα activity. In the antiproliferative assays, the compounds demonstrated activity against MCF-7 and T47-D tumor cells and nonhemolytic profile. Regarding toxicity, no acute effects were observed in the embryos. However, some compounds caused enzymatic and cardiac changes, particularly the CAIC, which increased SOD activity and altered heart rate compared to the control. These findings suggest potential antitumor action of the derivatives and indicate that substituting the acridine core with different cores does not interfere with their interaction and topoisomerase inhibition. Further investigations are required to assess possible toxicological effects, including reactive oxygen species generation.

Combining Near-Infrared Spectroscopy and Heart Rate Variability Derived Thresholds to Estimate the Critical Intensity of Exercise.

ABSTRACT: Fleitas-Paniagua, PR, de Almeida Azevedo, R, Trpcic, M, Murias, JM, and Rogers, B. Combining near-infrared spectroscopy and heart rate variability derived thresholds to estimate the critical intensity of exercise. J Strength Cond Res 38(1): e16-e24, 2024-Critical intensity determination often requires costly tools and several testing sessions. Alternative approaches display relatively large individual variation. Therefore, simpler estimations with improved precision are needed. This study evaluated whether averaging the heart rate (HR) and oxygen uptake (V̇O 2 ) responses associated with the muscle deoxyhemoglobin concentration breakpoint ([HHb] BP ) and the heart rate variability (HRV) given by the detrended fluctuation analysis second threshold (HRVT2) during ramp incremental (RI) test improved the accuracy of identifying the HR and V̇O 2 at the respiratory compensation point (RCP). Ten female and 11 male recreationally trained subjects performed a 15 W·minute -1 RI test. Gas exchange, near-infrared spectroscopy (NIRS), and RR interval were recorded to assess the RCP, [HHb] BP , and HRVT2. Heart rate (mean ± SD : 158 ± 14, 156 ± 13, 160 ± 14 and, 158 ± 12 bpm) and V̇O 2 (3.08 ± 0.69, 2.98 ± 0.58, 3.06 ± 0.65, and 3.02 ± 0.60 L·minute -1 ) at the RCP, [HHb] BP , HRVT2, and HRVT2&[HHb] BP average (H&H Av ), respectively, were not significantly different ( p > 0.05). The linear relationship between H&H Av and RCP was higher compared with the relationship between [HHb] BP vs RCP and HRVT2 vs RCP for both HR ( r = 0.85; r = 0.73; r = 0.79, p > 0.05) and V̇O 2 ( r = 0.94; r = 0.93; r = 0.91, p > 0.05). Intraclass correlation between RCP, [HHb] BP , HRVT2, and H&H AV was 0.93 for V̇O 2 and 0.79 for HR. The [HHb] BP and the HRVT2 independently provided V̇O 2 and HR responses that strongly agreed with those at the RCP. Combining [HHb] BP and the HRVT2 resulted in estimations of the V̇O 2 and HR at the RCP that displayed smaller variability compared with each modality alone.

Biochemical and teratogenic effects of a mixture of pyriproxyfen and glyphosate.

The mixture of agrochemicals can be made to improve pest control or accidentally. In this way, the effects on non-target organisms are a critical aspect of the environment and heath. Thus, this work aimed to show how a mixture of pyriproxyfen, and glyphosate can impair biochemical routes and embryonic development. Zebrafish embryos 0-72 hpf were exposed to 0.001-1 µg/mL of pyriproxyfen, glyphosate, and a mixture of both pesticides. The ADMETox was evaluated in silico. The FET-test was used to estimate teratogenic effects. The biochemical effects were estimated using AChE, SOD, and CAT as parameters. ROS generation was estimated using 30 µM H2DCF-DA and 5 µM DHE. The ADMETox reveals that intestinal absorption and P-glycoprotein are the main sites for PPx and Gly adsorption. The distribution parameters were diverse. PPx + Gly at 0.1 µg/mL leads to 50 % of lethality and at 1 µg/mL 100 % of lethality. PPx + Gly leads to a 22 % of lack of somite formation at 1 µg/mL. The heart rate was reduced by >10 % in all concentrations tested. The AChE has a decrease with IC20 19.6 µM and IC50 261.5 µM. SOD showed a reduction of 28 % to PPx and CAT was reduced by 58 % to PPx + Gly and Gly at 1 µg/mL. Glyphosate does not increase unspecific ROS generation. The superoxide generation was 2× higher in the PPx + Gly at 1 µg/mL. Summarily, was observed that the mixture of PPx + Gly potentiated the toxic effects. This finding suggests a possible synergism between the PPx and Gly even at lower concentrations.

Effect of ramp slope on intensity thresholds based on correlation properties of heart rate variability during cycling.

An index of heart rate variability (HRV), detrended fluctuation analysis (DFA a1) has gathered interest as a surrogate marker of exercise intensity boundaries. The aim of this report was to examine heart rate variability threshold (HRVT) behavior across different ramp incremental (RI) slopes. Seventeen participants completed a series of three RI (15, 30, and 45 W · min-1 slopes) with monitoring of gas exchange parameters, heart rate (HR) and HRV. HRVT1 was defined as the V̇O2 or HR at which DFA a1 reached 0.75 and the HRVT2 at which these values reached 0.5. HRVTs were compared by Pearson's r, Bland-Altman analysis, ICC3,1 , ANOVA, and paired t-testing. An excellent degree of reliability was seen across all three ramps, with an ICC3,1 of 0.93 and 0.88 for the HRVT1 V̇O2 and HR, respectively, and 0.90 and 0.92 for the HRVT2 V̇O2 and HR, respectively. Correlations between HRVT1/2 of the individual ramps were high with r values 0.84-0.95 for both HR and V̇O2 . Bland-Altman differences ranged between -1.4 and 1.2 mL · kg-1 · min-1 and -2 and +2 bpm. Paired t-testing showed no mean differences between any HRVT1/2 ramp comparisons. Cycling ramp slope does not appear to affect either HRVT1 or HRVT2 in terms of HR or V̇O2 .

Different ramp-incremental slopes elicit similar V̇o2max and fatigability profiles in females and males despite differences in peak power output.

The aim of this article is to investigate the effects of different ramp-incremental (RI) slopes on fatigability and its recovery in females and males. Ten females and 11 males performed RI tests with distinct slopes, in separated and randomized sessions, 15 (RI15), 30 (RI30), and 45 (RI45) W·min-1. Performance fatigability was assessed by femoral nerve electrical stimuli evoked during and after isometric maximal voluntary contraction (IMVC) of knee extensors at baseline and after task failure at min 0.5, 1.5, 2.5, 5, and 10. Maximal oxygen uptake (V̇o2max) and peak power output (POpeak) were also measured. There were significant and similar declines from pre- to post-RI test in RI15, RI30, and RI45 for IMVC (-23%; -25%; -25%, respectively; P < 0.05) and potentiated single twitch (-46%; -47%; -49%; P < 0.05), whereas voluntary activation did not change (-1%; -1%; 0%; P > 0.05). There were no RI condition effects, nor time × condition interaction for IMVC, potentiated single twitch and voluntary activation (all P > 0.05). V̇o2max was not different among RI15, RI30, and RI45 conditions (3.30, 3.29, and 3.26 L·min-1, respectively; P = 0.717), but POpeak was (272, 304, and 337 W, respectively; P < 0.001). Overall, performance fatigability profiles were similar between sexes after the RI tests and during recovery. In addition, during recovery, high-frequency doublets and single twitch recovered faster after RI30 and RI45 compared with RI15, regardless of sex (all P > 0.05 for sex differences). In conclusion, RI tests of different slopes that elicited similar V̇o2max but different POpeak did not affect the profile of performance fatigability at task failure in females and males.NEW & NOTEWORTHY It was unknown whether performance fatigability and its recovery are affected by different slopes in a ramp incremental (RI) test. It was also uncertain if females and males would respond differently. Performance fatigability was the same regardless of the RI slope adopted and the sex of the population, which was accompanied by similar maximal oxygen uptake but different power output achieved. The recovery of contractile function was similar between sexes but delayed after slower RI slopes.

A bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3.

Type I interferons (IFNs) are consequential cytokines in antibacterial defense. Whether and how bacterial pathogens inhibit innate immune receptor-driven type I IFN expression remains mostly unknown. By screening a library of enterohemorrhagic Escherichia coli (EHEC) mutants, we uncovered EhaF, an uncharacterized protein, as an inhibitor of innate immune responses including IFNs. Further analyses identified EhaF as a secreted autotransporter-a type of bacterial secretion system with no known innate immune-modulatory function-that translocates into host cell cytosol and inhibit IFN response to EHEC. Mechanistically, EhaF interacts with and inhibits the MiT/TFE family transcription factor TFE3 resulting in impaired TANK phosphorylation and consequently, reduced IRF3 activation and type I IFN expression. Notably, EhaF-mediated innate immune suppression promotes EHEC colonization and pathogenesis in vivo. Overall, this study has uncovered a previously unknown autotransporter-based bacterial strategy that targets a specific transcription factor to subvert innate host defense.

Children with malignancies and septic shock - an attempt to understand the risk factors

Abstract Objectives: To explain the high mortality of septic shock in children with cancer. Methods: A retrospective cohort from 2016 to 2020, of children aged 0 to 18 years, and septic shock. Results: The authors included 139 patients. Acute lymphocytic leukemia was the most frequent diagnosis (16.5%), and Gram-negative bacteria were the most frequent blood culture isolates (22.3%). There were 57 deaths in ICU (41%), 10 in the first 24 hours of shock (early death). A LASSO model with variables: neutropenia (coefficient 0.215), respiratory (0.81), hematological (1.41), and neurological (0.72) dysfunctions, age (-0.002) and solid tumor recurrence (0.34) generated AUC = 0.79 for the early death outcome. Survivors had significant differences in the PRISM-IV score (mean ± SD 10.9 ± 6.2 in the survivors, 14.1 ± 6.5 in the deceased, p = 0.004), and in the mean number of organ dysfunctions (3.2 ± 1.1 in the survivors, 3.8 ± 6.5 in the deceased, p < 0.001). A positive fluid balance in the first 24 hours of sepsis between 2% and 6% of body weight showed a reduction effect on the probability of death in ICU (hazard ratio 0.47, 95% CI 0.24-0.92, p = 0.027). The recurrence of any cancer was a predictor of in-hospital death, regardless of severity. Conclusions: Recurrence of any cancer is an important risk of sepsis-related death. A positive fluid balance between 20 and 60 mL/kg or 2% and 6% of body weight in the first 24 hours after the onset of sepsis is related to lower mortality.

Interaction study with DNA/HSA, anti-topoisomerase IIα, cytotoxicity and in vitro antiproliferative evaluations and molecular docking of indole-thiosemicarbazone compounds.

In this work we will discuss the antiproliferative evaluation and the possible mechanisms of action of indole-thiosemicarbazone compounds LTs with anti-inflammatory activity, previously described in the literature. In this perspective, some analyzes were carried out, such as the study of binding to human serum albumin (HSA) and to biological targets: DNA and human topoisomerase IIα (topo). Antiproliferative study was performed with DU-145, Jukart, MCF-7 and T-47D tumor lines and J774A.1, besides HepG2 macrophages and hemolytic activity. In the HSA interaction tests, the highest binding constant was 3.70 × 106 M-1, referring to LT89 and in the fluorescence, most compounds, except for LT76 and LT87, promoted fluorescent suppression with the largest Stern-Volmer constant for the LT88 3.55 × 104. In the antiproliferative assay with DU-145 and Jurkat strains, compounds LT76 (0.98 ± 0.10/1.23 ± 0.32 µM), LT77 (0.94 ± 0.05/1.18 ± 0.08 µM) and LT87 (0.94 ± 0.12/0.84 ± 0.09 µM) stood out, due to their IC50 values mentioned above. With the MCF-7 and T-47D cell lines, the lowest IC50 was presented by LT81 with values of 0.74 ± 0.12 µM and 0.68 ± 0.10 µM, respectively, followed by the compounds LT76 and LT87. As well as the positive control amsacrine, the compounds LT76, LT81 and LT87 were able to inhibit the enzymatic action of human Topoisomerase IIα.

Children with malignancies and septic shock - an attempt to understand the risk factors.

OBJECTIVES: To explain the high mortality of septic shock in children with cancer. METHODS: A retrospective cohort from 2016 to 2020, of children aged 0 to 18 years, and septic shock. RESULTS: The authors included 139 patients. Acute lymphocytic leukemia was the most frequent diagnosis (16.5%), and Gram-negative bacteria were the most frequent blood culture isolates (22.3%). There were 57 deaths in ICU (41%), 10 in the first 24 hours of shock (early death). A LASSO model with variables: neutropenia (coefficient 0.215), respiratory (0.81), hematological (1.41), and neurological (0.72) dysfunctions, age (-0.002) and solid tumor recurrence (0.34) generated AUC = 0.79 for the early death outcome. Survivors had significant differences in the PRISM-IV score (mean ± SD 10.9 ± 6.2 in the survivors, 14.1 ± 6.5 in the deceased, p = 0.004), and in the mean number of organ dysfunctions (3.2 ± 1.1 in the survivors, 3.8 ± 6.5 in the deceased, p < 0.001). A positive fluid balance in the first 24 hours of sepsis between 2% and 6% of body weight showed a reduction effect on the probability of death in ICU (hazard ratio 0.47, 95% CI 0.24-0.92, p = 0.027). The recurrence of any cancer was a predictor of in-hospital death, regardless of severity. CONCLUSIONS: Recurrence of any cancer is an important risk of sepsis-related death. A positive fluid balance between 20 and 60 mL/kg or 2% and 6% of body weight in the first 24 hours after the onset of sepsis is related to lower mortality.

A "Step-Ramp-Step" Protocol to Identify Running Speed and Power Associated with the Maximal Metabolic Steady State.

PURPOSE: A previously established Step-Ramp-Step (SRS) exercise protocol was able to accurately predict the work rate associated with the maximal metabolic steady state (MMSS) in cyclists. The purpose of this study was to determine whether a modified SRS protocol could predict the running speed and power associated with the MMSS. METHODS: Fifteen (8 male; 7 female) runners (V̇O 2max 54.5 [6.5] mL·kg -1 ·min -1 ) were recruited for this investigation composed of four to five visits. In the first visit, runners performed a moderate intensity step (MOD), an incremental exercise test, and a heavy intensity step (HVY), on a motorized treadmill. This SRS protocol was used to predict the running speed and power associated with the MMSS (i.e., the SRS-MMSS), where running power was assessed by a wearable device (Stryd) attached to each runner's shoe. Subsequent visits were used to confirm the maximal lactate steady state (MLSS) as a proxy measure of the MMSS (i.e., the MLSS-MMSS) and to validate the SRS-MMSS speed and power estimates. RESULTS: The estimated SRS-MMSS running speed (7.2 [0.6] mph) was significantly lower than confirmed running speed at MLSS-MMSS (7.5 [0.8] mph; bias = 3.6%, P = 0.005); however, the estimated SRS-MMSS running power (241 [35] W) was not different than the MLSS-MMSS confirmed running power (240 [37] W; bias = -0.6%; P = 0.435). V̇O 2 at SRS-MMSS (3.22 [0.49] L·min -1 ) was not different than respiratory compensation point (3.26 [0.58] L·min -1 ; P = 0.430). Similarly, V̇O 2 at MLSS-MMSS (3.30 [0.54] L·min -1 ) was not different than respiratory compensation point ( P = 0.438). CONCLUSIONS: The SRS protocol allows MMSS, as measured by MLSS, to be accurately determined using running power (Stryd), but not speed, in a single laboratory visit.

Time Course of Performance Fatigability during Exercise below, at, and above the Critical Intensity in Females and Males.

PURPOSE: This study aimed to investigate the time course and amplitude of performance fatigability during cycling at intensities around the maximal lactate steady state (MLSS) until task failure (TTF). METHODS: Ten females and 11 males were evaluated in eight visits: 1) ramp incremental test; 2-3) 30-min constant power output (PO) cycling for MLSS determination; and 4-8) cycling to TTF at PO relative to the MLSS of (i) -15%, (ii) -10 W, (iii) at MLSS, and (iv) +10 W, and (v) +15%. Performance fatigability was characterized by femoral nerve electrical stimulation of knee extensors at baseline; minutes 5, 10, 20, and 30; and TTF. Oxygen uptake, blood lactate concentration, muscle oxygen saturation, and perceived exertion were evaluated. RESULTS: Approximately 75% of the total performance fatigability occurred within 5 min of exercise, independently of exercise intensity, followed by a further change at minute 30. Contractile function declined more in males than females (all P < 0.05). At task failure, exercise duration declined from MLSS -15% to MLSS +15% (all P < 0.05), accompanied by a greater rate of decline after MLSS +15% and MLSS +10 compared with MLSS, MLSS -10 , and MLSS -15% for voluntary activation (-0.005 and -0.003 vs -0.002, -0.001 and -0.001%·min -1 , respectively) and contractile function (potentiated single twitch force, -0.013 and -0.009 vs -0.006, -0.004 and -0.004%·min -1 , respectively). CONCLUSIONS: Whereas the time course of performance fatigability responses was similar regardless of exercise intensity and sex, the total amplitude and rate of change were affected by the distinct metabolic disturbances around the MLSS, leading to different performance fatigability etiologies at task failure.

Impact of Metabolic Risk Factors on COVID-19 Clinical Outcomes: An Extensive Review.

BACKGROUND: Cardiovascular (CV) risk factors, particularly cardiometabolic, seem to be associated with heightened severity and increased morbimortality in patients infected with the novel Coronavirus disease-2019 (COVID-19). METHODS: A thorough scoping review was conducted to elucidate and summarize the latest evidence for the effects of adverse cardiac metabolic profiles on the severity, morbidity, and prognosis of COVID-19 infection. RESULTS: The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is complex, being characterized by viral-induced immune dysregulation and hypercytokinemia, particularly in patients with critical disease, evolving with profound endothelial dysfunction, systemic inflammation, and prothrombotic state. Moreover, cardiovascular comorbidities such as diabetes are the most prevalent amongst individuals requiring hospitalization, raising concerns towards the clinical evolution and prognosis of these patients. The chronic proinflammatory state observed in patients with cardiovascular risk factors may contribute to the immune dysregulation mediated by SARS-CoV-2, favoring more adverse clinical outcomes and increased severity. Cardiometabolism is defined as a combination of interrelated risk factors and metabolic dysfunctions such as dyslipidemia, insulin resistance, impaired glucose tolerance, and central adiposity, which increase the likelihood of vascular events, being imperative to specifically analyze its clinical association with COVID-19 outcomes. CONCLUSION: DM and obesity appears to be important risk factors for severe COVID-19. The chronic proinflammatory state observed in patients with excess visceral adipose tissue (VAT) possibly augments COVID-19 immune hyperactivity leading to more adverse clinical outcomes in these patients.

Arbovirus outbreak in a rural region of the Brazilian Amazon.

BACKGROUND: An outbreak of febrile illness was reported from January to February 2018 in the Expedito Ribeiro Settlement, ​​Santa Bárbara do Pará municipality, Pará State, Brazil. OBJECTIVE: This study aimed to investigate the pathogenic agent responsible for the outbreak and the circulation of arboviruses in the region. STUDY DESIGN: We analyzed 94 individuals through laboratory tests for arboviruses. Forty out of 94 individuals were asymptomatic but were living with or near febrile cases, and 55 participants were symptomatic. RESULTS: Our results showed that 51.1% of the investigated individuals were positive for arboviruses (Oropouche, Mayaro, and Chikungunya), of which 77.8% were symptomatic. We detected 93.7% of positive cases for Oropouche infection, 2.1% for Mayaro fever, and 4.2% were positive for both Oropouche and Chikungunya infection. CONCLUSION: Oropouche virus was mainly responsible for the outbreak; however, we also detected a few Chikungunya and Mayaro fever cases. Serologic assays showed evidence of arboviruses circulation of different genera in the area.

Tracheostomy practices in children on mechanical ventilation: a systematic review and meta-analysis

Abstract Objective: To evaluate current practices of tracheostomy in children regarding the ideal timing of tracheostomy placement, complications, indications, mortality, and success in decannulation. Source of data: The authors searched PubMed, Embase, Cochrane Library, Google Scholar, and complemented by manual search. The guidelines of PRISMA and MOOSE were applied. The quality of the included studies was evaluated with the Newcastle-Ottawa Scale. Information extracted included patients' characteristics, outcomes, time to tracheostomy, and associated complications. Odds ratios (ORs) with 95% CIs were computed using theMantel-Haenszel method. Synthesis of data: Sixty-six articles were included in the qualitative analysis, and 8 were included in the meta-analysis about timing for tracheostomy placement. The risk ratio for "death in hospital outcome" did not show any benefit from performing a tracheostomy before or after 14 days of mechanical ventilation (p = 0.49). The early tracheostomy before 14 days had a great impact on the days of mechanical ventilation (-26 days in mean difference, p < 0.00001). The authors also found a great reduction in hospital length of stay (-31.4 days, p < 0.008). For the days in PICU, the mean reduction was of 14.7 days (p < 0.007). Conclusions: The meta-analysis suggests that tracheostomy performed in the first 14 days of ventilation can reduce the time spent on the ventilator, and the length of stay in the hospital, with no effect on mortality. The decision to perform a tracheostomy early or late may be more dependent on the baseline disease than on the time spent on ventilation.