TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling.

The sensation of pain is associated with increased mortality, but it is unknown whether pain perception can directly affect aging. We find that mice lacking TRPV1 pain receptors are long-lived, displaying a youthful metabolic profile at old age. Loss of TRPV1 inactivates a calcium-signaling cascade that ends in the nuclear exclusion of the CREB-regulated transcriptional coactivator CRTC1 within pain sensory neurons originating from the spinal cord. In long-lived TRPV1 knockout mice, CRTC1 nuclear exclusion decreases production of the neuropeptide CGRP from sensory endings innervating the pancreatic islets, subsequently promoting insulin secretion and metabolic health. In contrast, CGRP homeostasis is disrupted with age in wild-type mice, resulting in metabolic decline. We show that pharmacologic inactivation of CGRP receptors in old wild-type animals can restore metabolic health. These data suggest that ablation of select pain sensory receptors or the inhibition of CGRP are associated with increased metabolic health and control longevity.

Immunometabolic crosstalk in Aedes fluviatilis and Wolbachia pipientis symbiosis.

Wolbachia pipientis is a maternally transmitted symbiotic bacterium that mainly colonizes arthropods, potentially affecting different aspects of the host's physiology, e.g., reproduction, immunity, and metabolism. It has been shown that Wolbachia modulates glycogen metabolism in mosquito Aedes fluviatilis (Ae. fluviatilis). Glycogen synthesis is controlled by the enzyme GSK3, which is also involved in immune responses in both vertebrate and invertebrate organisms. Here we investigated the mechanisms behind immune changes mediated by glycogen synthase kinase ß (GSK3ß) in the symbiosis between Ae. fluviatilis and W. pipientis using a GSK3ß inhibitor or RNAi-mediated gene silencing. GSK3ß inhibition or knockdown increased glycogen content and Wolbachia population, together with a reduction in Relish2 and gambicin transcripts. Furthermore, knockdown of Relish2 or Caspar revealed that the immunodeficiency pathway acts to control Wolbachia numbers in the host. In conclusion, we describe for the first time the involvement of GSK3ß in Ae. fluviatilis immune response, acting to control the Wolbachia endosymbiotic population.

Sleep "ON", sleep better! Positive effects of levodopa on sleep behaviour in people with Parkinson's disease.

People with Parkinson's disease experience reduced sleep quality compared with their peers. Levodopa may have a direct effect on sleep macrostructure or may improve sleep by enhancing nocturnal motor performance. Therefore, it is important to understand the acute effects of withdrawing levodopa on sleep measures in Parkinson's disease. The purpose of this study was to compare the estimated objective and subjective sleep measures of people with Parkinson's disease sleeping under (ON-night) versus without (OFF-night) the effects of the last daily dopaminergic medication before going to bed. A total of 23 people with Parkinson's disease were instructed to wear an actigraphy device for 4 consecutive nights to objectively measure the sleep behaviour. Subjective sleep measure was assessed each morning using a Likert scale. Participants slept for 3 nights on ON-night and 1 night on OFF-night. They were instructed not to take their last dose of levodopa before going to bed in OFF-night. Sleeping in ON- versus OFF-night increased total sleep time (7.8%, p = 0.032) and sleep efficiency (3.7%, p = 0.019), and decreased duration and number of wakes after sleep onset (22.3%, p = 0.050; and 29.2%, p = 0.013, respectively). However, subjective sleep analysis indicated no significant differences between the two conditions. From a clinical point of view, our results suggest that sleeping on ON-night resulted in an improvement in estimated objective sleep measures compared with sleeping on OFF-night. From a methodological point of view, our findings emphasize the importance of relying on objective sleep measurements to accurately assess OFF-night sleep behaviour in people with Parkinson's disease.

Four-week experimental plus 1-week taper period using live high train low does not alter muscle glycogen content.

This study aimed to investigate the effects of a 4-week live high train low (LHTL; FiO2 ~ 13.5%), intervention, followed by a tapering phase, on muscle glycogen concentration. Fourteen physically active males (28 ± 6 years, 81.6 ± 15.4 kg, 179 ± 5.2 cm) were divided into a control group (CON; n = 5), and the group that performed the LHTL, which was exposed to hypoxia (LHTL; n = 9). The subjects trained using a one-legged knee extension exercise, which enabled four experimental conditions: leg training in hypoxia (TLHYP); leg control in hypoxia (CLHYP, n = 9); leg trained in normoxia (TLNOR, n = 5), and leg control in normoxia (CLNOR, n = 5). All participants performed 18 training sessions lasting between 20 and 45 min [80-200% of intensity corresponding to the time to exhaustion (TTE) reached in the graded exercise test]. Additionally, participants spent approximately 10 h day-1 in either a normobaric hypoxic environment (14.5% FiO2; ~ 3000 m) or a control condition (i.e., staying in similar tents on ~ 530 m). Thereafter, participants underwent a taper protocol consisting of six additional training sessions with a reduced training load. SpO2 was lower, and the hypoxic dose was higher in LHTL compared to CON (p < 0.001). After 4 weeks, glycogen had increased significantly only in the TLNOR and TLHYP groups and remained elevated after the taper (p < 0.016). Time to exhaustion in the LHTL increased after both the 4-week training period and the taper compared to the baseline (p < 0.001). Although the 4-week training promoted substantial increases in muscle glycogen content, TTE increased in LHTL condition.

Effect of Aerobic Training with Blood Flow Restriction on Strength and Hypertrophy: A Meta-analysis.

The objective of this meta-analysis is to compare the effects on muscle strength and hypertrophy of low and high-intensity aerobic training with BFR (LI-BFR and HI-BFR) versus low and high-intensity aerobic training without BFR (LI and HI). The search was performed in five databases, by two independent researchers, and the terms and keywords used to optimize the searches were related to blood flow restriction and aerobic training. All studies were evaluated for methodological quality using the PEDro scale and for quality of evidence using the GRADE system. Meta-analyses were conducted using RevMan software. After data extraction, 11 studies met all eligibility criteria and were included in the systematic review. The results of the overall analysis between LI-BFR vs. LI showed a significant difference in muscle strength of knee extensors; for hypertrophy, LI was superior to LI-BFR with clinical relevance. Comparing HI-BFR vs. HI there was no superiority for muscle strength. In conclusion, for strength gains very low-quality evidence was found to support no superiority between LI-BFR and HI-BFR compared to LI and HI, respectively. For muscle hypertrophy, superiority of LI was found compared to LI-BFR, with a very low level of evidence.

Reliability of Anaerobic Contributions during a Single Exhaustive Knee-extensor Exercise.

The total anaerobic contribution (AC[La-]+PCr) is a valid and reliable methodology. However, the active muscle mass plays an important role in the AC[La-]+PCr determination, which might influence its reliability. Thus, this study aimed to investigate the effects of two exhaustive intensities on the reliability of the AC[La-]+PCr during a one-legged knee extension (1L-KE) exercise. Thirteen physically active males were submitted to a graded exercise to determine the peak power output (PPO) in the 1L-KE. Then, two constant-load exercises were conducted to task failure at 100% (TTF100) and 110% (TTF110) of PPO, and the exercises were repeated on a third day. The blood lactate accumulation and the oxygen uptake after exercise were used to estimate the anaerobic lactic and alactic contributions, respectively. Higher values of AC[La-]+PCr were found after the TTF100 compared to TTF110 (p=0.042). In addition, no significant differences (p=0.432), low systematic error (80.9 mL), and a significant ICC (0.71; p=0.004) were found for AC[La-]+PCr in the TTF100. However, an elevated coefficient of variation was found (13.7%). In conclusion, we suggest the use of the exhaustive efforts performed at 100% of the PPO with the 1L-KE model, but its elevated individual variability must be carefully considered in future studies.

3-min All-out Test to Evaluate Aerobic and Anaerobic Indexes in Court Team Sports.

This study aimed to test the reproducibility of the 3-min all-out effort applied using shuttle running and compare its values to aerobic parameters. On the first day, 14 futsal players underwent an exhaustive test to determine the maximal incremental speed (MIS) and anaerobic threshold (AnT). On the second day, the participants performed the 3-min all-out effort (n=14), which was repeated after 48 h (third day) to test its reproducibility (n=11). Peak oxygen consumption (V̇ O2PEAK) and peak blood lactate concentrations ([La-]) were determined from 3-min all-out efforts performed through a 20-m shuttle run on the official court. The distance covered, mean speed, and critical speed (CS) during the 3-min all-out presented direct relationships with aerobic parameters determined through the incremental test (r>0.62). The distance covered above CS (D') presented a direct relationship with peak lactate concentrations induced by a 3-min all-out effort (r=0.81). Despite the acceptable levels of reproducibility observed for most of the 3-min all-out variables, the minimal detectable change for D' was high (72%). Our results demonstrated the potential use of mean speed to evaluate aerobic fitness. However, the applicability of the 3-min all-out shuttle run test to monitor training adaptations should be avoided, at least in nonexperienced athletes.

Toxicity of Trixis vauthieri DC essential oil on Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae), a proven vector of visceral leishmaniasis in Brazil.

BACKGROUND OBJECTIVES: In Brazil, one of the visceral leishmaniasis control measures in urban environments is the elimination of Lutzomyia longipalpis, which occurs through the application of pyrethroid insecticides with residual action in homes and outbuildings. Due to the loss of sensitivity of this vector to these insecticides, the search for more efficient insecticide compounds against L. longipalpis has been intensified. The objective of this work was to evaluate the toxicity of Trixis vauthieri essential oil on adult sandflies of the species L. longipalpis, and identify the phytochemical composition of these essential oils. METHODS: Essential oils from leaves collected from T. vauthieri at different times were obtained at concentrations of 5, 10 and 20 mg/mL. Twenty sandflies were exposed to the essential oils and the mortality was evaluated after 1, 2, 4, 16, 24, 48 and 72 h. The chemical constituents of the essential oil were also identified. RESULTS: The essential oils of T. vauthieri at a concentration of 20 mg/mL were the most toxic to sandflies, reaching a mortality rate of 98.33% and 95%, respectively, after 72 h of exposure. The analysis of chemical constituents revealed the presence of triterpenes and/or steroids, tannins, flavonoids, alkaloids, saponins and coumarins. INTERPRETATION CONCLUSION: The results obtained suggest that T. vauthieri essential oil is fairly promising as an insecticidal potential against L. longipalpis. A more detailed analysis of the oil's phytochemical composition is necessary to identify active and pure compounds that can be used in vector control of visceral leishmaniasis.

Exercise modifies hypothalamic connectivity and brain functional networks in women after bariatric surgery: a randomized clinical trial.

BACKGROUND: Obesity is a disease that may involve disrupted connectivity of brain networks. Bariatric surgery is an effective treatment for obesity, and the positive effects on obesity-related conditions may be enhanced by exercise. Herein, we aimed to investigate the possible synergistic effects of Roux-en-Y Gastric Bypass (RYGB) and exercise training on brain functional networks. METHODS: Thirty women eligible for bariatric surgery were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 15, age = 41.0 ± 7.3 years) or RYGB plus Exercise Training (RYGB + ET: n = 15, age = 41.9 ± 7.2 years). Clinical, laboratory, and brain functional connectivity parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6-month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET). RESULTS: Exercise superimposed on bariatric surgery (RYGB + ET) increased connectivity between hypothalamus and sensorial regions (seed-to-voxel analyses of hypothalamic connectivity), and decreased default mode network (DMN) and posterior salience (pSAL) network connectivity (ROI-to-ROI analyses of brain networks connectivity) when compared to RYGB alone (all p-FDR < 0.05). Increases in basal ganglia (BG) network connectivity were only observed in the exercised training group (within-group analyses). CONCLUSION: Exercise training is an important component in the management of post-bariatric patients and may improve the hypothalamic connectivity and brain functional networks that are involved in controlling food intake. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02441361.

α-Lipoic Acid as Adjunctive Treatment for Schizophrenia: A Randomized Double-Blind Study.

BACKGROUND/PURPOSE: There is evidence for low endogenous antioxidant levels and oxidative imbalance in patients with schizophrenia. A previous open-label study with α-lipoic acid (ALA), a potent antioxidant, improved patients' negative and cognitive symptoms and markers of lipid peroxidation. Here we report the results of a randomized double-blind, placebo-controlled study to verify the response of patients with schizophrenia to adjunctive treatment with ALA (100 mg/d) in a 4-month follow-up. METHODS: We conducted a 16-week, double-blind, placebo-controlled study of ALA at 100 mg/d dosages. We compared negative and positive symptoms, cognitive function, extrapyramidal symptoms, body mass index, and oxidative/inflammatory parameters between placebo and control groups. RESULTS: We found no significant improvement in body mass index, cognition, psychopathology, antipsychotic adverse effects, or oxidative stress and inflammation in the experimental group compared with placebo. The whole group of patients improved in several measures, indicating a strong placebo effect in this population. A surprising finding was a significant decrease in red blood cells, white blood cells, and platelets in the group treated with ALA. CONCLUSIONS: The decrease in red blood cells, white blood cells, and platelet counts requires further investigation and attention when prescribing ALA for patients with schizophrenia.

Vitamin D (VD3) Intensifies the Effects of Exercise and Prevents Alterations of Behavior, Brain Oxidative Stress, and Neuroinflammation, in Hemiparkinsonian Rats.

In the present study, we investigated the effects of physical exercise in the presence of Vitamin D3 (VD3), on 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats. The animals were divided into sham-operated (SO), 6-OHDA-lesioned, and 6-OHDA-lesioned plus VD3 (1 µg/kg, 21 days), in the absence (no exercise, NE) and presence (with exercise, WE) of physical exercise on a treadmill (30 min, speed of 20 cm/s, once a day/21 days). This procedure started, 24 h after the stereotaxic surgery (injections of 6-OHDA into the right striatum). The animals were then subjected to behavioral (rotarod, open field, and apomorphine tests) and their brain areas were dissected for neurochemical, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) determinations, and immunohistochemical studies for tyrosine hydroxylase (TH), dopamine transporter (DAT), and vitamin D receptor (VD3R). The effects on the brain oxidative stress: nitrite/nitrate, glutathione (GSH), and malondialdehyde (MDA) measurements were also evaluated. Behavioral changes of the 6-OHDA lesioned group were improved by exercise plus VD3. Similar results were observed in dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations increased by exercise and VD3, compared with SO groups. Additionally, tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoexpressions were decreased in the 6-OHDA-lesioned groups, with values normalized after exercise and VD3. The VD3 receptor immunoexpression decreased in the 6-OHDA (NE) group, and this was attenuated by exercise, especially after VD3. While 6-OHDA lesions increased, VD3 supplementation decreased the oxidative stress, which was intensified by exercise. VD3 showed neuroprotective properties that were intensified by physical exercise. These VD3 actions on hemiparkinsonian rats are possibly related to its antioxidant and anti-inflammatory effects.

Non-standard diagnostic assessment reliability in psychiatry: a study in a Brazilian outpatient setting using Kappa.

The use of Structured Diagnostic Assessments (SDAs) is a solution for unreliability in psychiatry and the gold standard for diagnosis. However, except for studies between the 50 s and 70 s, reliability without the use of Non-SDAs (NSDA) is seldom tested, especially in non-Western, Educated, Industrialized, Rich, and Democratic (WEIRD) countries. We aim to measure reliability between examiners with NSDAs for psychiatric disorders. We compared diagnostic agreement after clinician change, in an outpatient academic setting. We used inter-rater Kappa measuring 8 diagnostic groups: Depression (DD: F32, F33), Anxiety Related Disorders (ARD: F40-F49, F50-F59), Personality Disorders (PD: F60-F69), Bipolar Disorder (BD: F30, F31, F34.0, F38.1), Organic Mental Disorders (Org: F00-F09), Neurodevelopment Disorders (ND: F70-F99) and Schizophrenia Spectrum Disorders (SSD: F20-F29). Cohen's Kappa measured agreement between groups, and Baphkar's test assessed if any diagnostic group have a higher tendency to change after a new diagnostic assessment. We analyzed 739 reevaluation pairs, from 99 subjects who attended IPUB's outpatient clinic. Overall inter-rater Kappa was moderate, and none of the groups had a different tendency to change. NSDA evaluation was moderately reliable, but the lack of some prevalent hypothesis inside the pairs raised concerns about NSDA sensitivity to some diagnoses. Diagnostic momentum bias (that is, a tendency to keep the last diagnosis observed) may have inflated the observed agreement. This research was approved by IPUB's ethical committee, registered under the CAAE33603220.1.0000.5263, and the UTN-U1111-1260-1212.

Decrease in cognitive performance and increase of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with higher doses of antipsychotics in women with schizophrenia: a cross-sectional study.

BACKGROUND: We explored the relationship between symptoms, cognitive performance, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) (three markers of inflammation), and antipsychotic dose (in chlorpromazine units) in male and female patients with schizophrenia. METHODS: We conducted a cross-sectional analysis in patients with schizophrenia of the complete blood count and the results of neuropsychological testing, using the Welch t-test to compare groups and the Pearson test for correlations. RESULTS: We found that the NLR and the PLR are higher among women with schizophrenia when compared with men. In women, the NLR and the PLR correlate positively with antipsychotic drug dose and inversely with a working memory test (Direct Digit Span). Higher doses of antipsychotics are associated with worse working and semantic memory and mental flexibility in the women in our sample. CONCLUSION: Higher doses of antipsychotics were associated with worse working and semantic memory and mental flexibility in women with schizophrenia. No such correlations were present in men, suggesting that, in female patients, cognitive performance deteriorates as the antipsychotic dose is increased, a finding that could be mediated by inflammatory mechanisms, given the demonstrated relationship to biomarkers of inflammation - e.g., the NLR and the PLR. TRIAL REGISTRATION: NCT03788759 (ClinicalTrials.gov).

Efficacy of methenamine with methylthioninium in the treatment of dysuria: a randomized clinical study.

INTRODUCTION AND HYPOTHESIS: Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional symptomatic treatment. This study evaluated the combination of methenamine 250 mg and methylthioninium chloride 20 mg in the treatment of dysuria versus phenazopyridine. METHODS: This was a multicenter, single-blind, randomized, superiority clinical trial, including individuals over 18 with dysuria and a score ≥ 5 points on the pre-treatment categorical scale for pain. The primary outcome was the proportion of participants presenting excellent clinical response within 24 h after treatment. Improvement up to 72 h, time to reach improvement, sustained healing, investigators' opinion, and safety were also evaluated. RESULTS: Three hundred and fifteen participants were evaluated. Demographic characteristics and symptoms of dysuria were comparable between groups at baseline. The difference in the excellent response rate between treatments within 24 h was 12.7% (95% CI 6.16, 19.21) for pain, 9.4% (95% CI 3.32, 15.39) for burning, and 12.7% (95% CI 6.37, 18.99) for burning on urination, all in favor of the test drug, which was also superior from 36 to 48 h. Treatments were similar concerning time to reach the absence of symptoms and in the percentage of participants with sustained healing after 72 h. CONCLUSIONS: The association of methenamine with methylthioninium is superior to phenazopyridine in the treatment of dysuria.

The role of Gestational Diabetes Mellitus and pelvic floor 3D-ultrasound assessment during pregnancy predicting urinary incontinence: a prospective cohort study.

Postpartum urinary incontinence may have a severe impact on women's health. Despite pregnancy and parturition being the most recognized risk factors, methods to identify new pregnant predictor risk factors are needed. Our study investigated the Gestational Diabetes Mellitus, clinical and pelvic floor 3D-ultrasound markers in pregnant women as predictors for 6-18 months of urinary incontinence. This prospective cohort study included nulliparous pregnant women submitted to Gestational Diabetes Mellitus screening in the second trimester. Pelvic floor 3D Ultrasound was performed at the second and third trimesters of gestation to evaluate the pelvic floor muscles and functions. Clinical data, the ICIQ-SF, and ISI questionnaires for urinary incontinence were applied in the third trimester and 6-18 months postpartum. Univariate analysis (P < .20) to extract risk factors variables and multivariate logistic regression analysis (P < .05) to obtain the adjusted relative ratio for urinary incontinence were performed. A total of 93 participants concluded the follow-up. Using the variables obtained by univariate analysis and after adjustments for potential confounders, multivariate analysis revealed that Gestational Diabetes Mellitus exposure was a solid and independent risk factor for 6-18 months of urinary incontinence (Adjusted RR 8.08; 95%CI 1.17-55.87; P:0.034). In addition, a higher Hiatal area observed in distension maneuver from the second to third trimester was negatively associated (Adjusted RR 0.96; 95%CI 0.93-0.99; P:0.023). In conclusion, Gestational Diabetes Mellitus was positively associated with 6-18 months of urinary incontinence, and higher Hiatal area distension was negatively associated.

Sleep quality and regular physical activity in reducing cardiac risk.

BACKGROUND: Adolescents with sedentary behavior, spending many hours in front of the television and electronic devices, develop early involvement of cardiovascular disease and obesity. These sedentary behaviors increased significantly in this age group during the pandemic of 2020/2021. Sleep directly influences aspects of health, such as blood pressure and cardiac autonomic balance and exercise has a protective effect on these same physiological parameters. OBJECTIVE: This study aimed to examine whether or not physically active adolescents positively influence HRV and cardiovascular parameters despite poor sleep quality. METHODS: This is an analytic and transversal study. Sleep quality, physical activity levels, blood pressure, and heart rate variability (HRV) were measured. Two-way ANOVA and Tuckey post hoc test evaluated the difference between groups. RESULTS: Among 352 adolescents entrolled, mean age was 15.8 ± 0.24 years. It was observed that compared to the physically active group with poor sleep quality, the sedentary poor sleep quality group presented a more significant deficit in blood pressure and autonomic parameters such as pNN50, SD1, and HF. CONCLUSION: Adolescents who practiced physical activity regularly have shown better HRV and sleep quality compared with sedentary adolescents.

Recovery of kicking kinematics and performance following repeated high-intensity running bouts in the heat: Can a rapid local cooling intervention help young soccer players?

The effects of a cooling strategy following repeated high-intensity running (RHIR) on soccer kicking performance in a hot environment (>30ºC) were investigated in youth soccer players. Fifteen academy under-17 players participated. In Experiment 1, players completed an all-out RHIR protocol (10×30 m, with 30s intervals). In Experiment 2 (cross-over design), participants performed this running protocol under two conditions: (1) following RHIR 5 minutes of cooling where ice packs were applied to the quadriceps/hamstrings, (2) a control condition involving passive resting. Perceptual measures [ratings of perceived exertion (RPE), pain and recovery], thigh temperature and kick-derived video three-dimensional kinematics (lower limb) and performance (ball speed and two-dimensional placement indices) were collected at baseline, post-exercise and intervention. In Experiment 1, RHIR led to small-to-large impairments (p < 0.03;d = -0.42--1.83) across perceptual, kinematic and performance measures. In experiment 2, RPE (p < 0.01; Kendall's W = 0.30) and mean radial error (p = 0.057; η2 = 0.234) increased only post-control. Significant small declines in ball speed were also observed post-control (p < 0.05; d = 0.35). Post-intervention foot centre-of-mass velocity was moderately faster in the cooling compared to control condition (p = 0.04; d = 0.60). In youth soccer players, a short cooling period was beneficial in counteracting declines in kicking performance, in particular ball placement, following intense running activity in the heat.

Piplartine-Inspired 3,4,5-Trimethoxycinnamates: Trypanocidal, Mechanism of Action, and In Silico Evaluation.

Chagas disease (CD) is one of the main neglected tropical diseases that promote relevant socioeconomic impacts in several countries. The therapeutic options for the treatment of CD are limited, and parasite resistance has been reported. Piplartine is a phenylpropanoid imide that has diverse biological activities, including trypanocidal action. Thus, the objective of the present work was to prepare a collection of thirteen esters analogous to piplartine (1-13) and evaluate their trypanocidal activity against Trypanosoma cruzi. Of the tested analogues, compound 11 ((E)-furan-2-ylmethyl 3-(3,4,5-trimethoxyphenyl)acrylate) showed good activity with IC50 values = 28.21 ± 5.34 µM and 47.02 ± 8.70 µM, against the epimastigote and trypomastigote forms, respectively. In addition, it showed a high rate of selectivity to the parasite. The trypanocidal mechanism of action occurs through the induction of oxidative stress and mitochondrial damage. In addition, scanning electron microscopy showed the formation of pores and leakage of cytoplasmic content. Molecular docking indicated that 11 probably produces a trypanocidal effect through a multi-target mechanism, including affinity with proteins CRK1, MPK13, GSK3B, AKR, UCE-1, and UCE-2, which are important for the survival of the parasite. Therefore, the results suggest chemical characteristics that can serve for the development of new trypanocidal prototypes for researching drugs against Chagas disease.

Herpesvirus and neurological manifestations in patients with severe coronavirus disease.

BACKGROUND: Certain clinical manifestations of coronavirus disease (COVID-19) mimic those associated with human herpesvirus (HHV) infection. In this study, we estimated the prevalence of herpesvirus in patients with COVID-19 and determined if coinfection is associated with poorer outcomes and neurological symptoms. METHODS: We analyzed samples of 53 patients diagnosed with COVID-19. The samples were evaluated for the presence of alphaherpesviruses, betaherpesviruses, and gammaherpesviruses, and the viral loads were quantified using quantitative polymerase chain reaction (qPCR) method. RESULTS: Among the patients, in 79.2% had detection at least one type of herpesvirus. HHV-6 (47.2%), cytomegalovirus (43.3%), and HHV-7 (39.6%) showed the highest detection rates. Patients with a high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load were more likely to show herpes simplex virus 1 detection (p = 0.037). Among patients coinfected with SARS-CoV-2 and HHVs, 26.4% showed central nervous system-associated neurological symptoms and herpetic manifestations. A statistically significant association was observed between neurological changes and HHV-6 detection (p = 0.034). CONCLUSIONS: The findings showed a high prevalence of herpesvirus in patients with COVID-19. Furthermore, even though SARS-CoV-2 and HHV coinfection was not associated with poorer outcomes, the findings demonstrated the association between neurological symptoms and HHV-6 detection.

Pelvic floor muscle dysfunction at 3D transperineal ultrasound in maternal exposure to gestational diabetes mellitus: A prospective cohort study during pregnancy.

AIM: This study aimed to assess, for the first time, the dynamic morphometry of pelvic floor muscles (PFM) using three-dimensional transperineal ultrasound (3D-TPUS) and its progression at two-time points of gestation between women with and without gestational diabetes mellitus (GDM), and whether the PFM dysfunction is connected to GDM. METHODS: The study comprised 83 consecutive pregnant women with (n = 38) and without (n = 45) GDM screened at 24-30 and 38-40 weeks of gestation. 3D-TPUS and a mobility test were used to quantify PFM dynamic morphometry during maximum contraction and the Valsalva maneuver. RESULTS: When compared to the control group, GDM women had no significant variations in all levator hiatal dimensions at 24-30 weeks of gestation. Meanwhile, women with GDM experienced an increase in levator hiatal area (LHa) (p < 0.000) during PFM contraction and enlargement in LHa (p < 0.001) during Valsalva maneuver (p = 0.010) at 38-40 weeks of gestation. As a result, the mobility index among GDM women had a lower value (p = 0.000). The dynamic morphometry development of PFM in GDM women at two stages during pregnancy revealed a substantial decrease (p = 0.000) in all LHa dimensions of contraction, distension, and mobility. CONCLUSIONS: Using 3D-TPUS, we found that GDM women had a specific pattern of PFM functional changes in the third trimester of pregnancy. These initial findings revealed alterations in PFM functionality, such as decreased contractility, distensibility, or mobility. This dysfunctional PFM could contribute to the long-term development of pelvic floor dysfunction years after a GDM pregnancy.