Innovative infrastructure to access Brazilian fungal diversity using deep learning.

In the present investigation, we employ a novel and meticulously structured database assembled by experts, encompassing macrofungi field-collected in Brazil, featuring upwards of 13,894 photographs representing 505 distinct species. The purpose of utilizing this database is twofold: firstly, to furnish training and validation for convolutional neural networks (CNNs) with the capacity for autonomous identification of macrofungal species; secondly, to develop a sophisticated mobile application replete with an advanced user interface. This interface is specifically crafted to acquire images, and, utilizing the image recognition capabilities afforded by the trained CNN, proffer potential identifications for the macrofungal species depicted therein. Such technological advancements democratize access to the Brazilian Funga, thereby enhancing public engagement and knowledge dissemination, and also facilitating contributions from the populace to the expanding body of knowledge concerning the conservation of macrofungal species of Brazil.

Pathophysiology of chikungunya virus infection associated with fatal outcomes.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.

Thyroid hormone induces restrictive cardiomyopathy in ß1-adrenoceptor knockout mice.

The purpose of this study was to characterize the role of ß1-AR signaling and its cross-talk between cardiac renin-angiotensin system and thyroid-hormone-induced cardiac hypertrophy. T3 was administered at 0.5 mg·kg-1·day-1 for 10 days in ß1-KOT3 and WTT3 groups, while control groups received vehicle alone. Echocardiography and myocardial histology was performed; cardiac and serum ANGI/ANGII and ANP and cardiac levels of p-PKA, p-ERK1/2, p-p38-MAPK, p-AKT, p-4EBP1, and ACE were measured. WTT3 showed decreased IVSTd and increased LVEDD versus WTsal (p < 0.05). ß1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus ß1-KOsal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WTT3 versus ß1-KOT3 (p < 0.05). Cardiac ACE expression was increased in T3-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or ß1-KOT3, p-4EBP1 was elevated in ß1-KO animals, and p-ERK1/2 was up-regulated in ß1-KOT3. These findings suggest that ß1-AR signaling is crucial for TiCH.

A Shortcut from Genome to Drug: The Employment of Bioinformatic Tools to Find New Targets for Gastric Cancer Treatment.

Gastric cancer (GC) is a highly heterogeneous, complex disease and the fifth most common cancer worldwide (about 1 million cases and 784,000 deaths worldwide in 2018). GC has a poor prognosis (the 5-year survival rate is less than 20%), but there is an effort to find genes highly expressed during tumor establishment and use the related proteins as targets to find new anticancer molecules. Data were collected from the Gene Expression Omnibus (GEO) bank to obtain three dataset matrices analyzing gastric tumor tissue versus normal gastric tissue and involving microarray analysis performed using the GPL570 platform and different sources. The data were analyzed using the GEPIA tool for differential expression and KMPlot for survival analysis. For more robustness, GC data from the TCGA database were used to corroborate the analysis of data from GEO. The genes found in in silico analysis in both GEO and TCGA were confirmed in several lines of GC cells by RT-qPCR. The AlphaFold Protein Structure Database was used to find the corresponding proteins. Then, a structure-based virtual screening was performed to find molecules, and docking analysis was performed using the DockThor server. Our in silico and RT-qPCR analysis results confirmed the high expression of the AJUBA, CD80 and NOLC1 genes in GC lines. Thus, the corresponding proteins were used in SBVS analysis. There were three molecules, one molecule for each target, MCULE-2386589557-0-6, MCULE-9178344200-0-1 and MCULE-5881513100-0-29. All molecules had favorable pharmacokinetic, pharmacodynamic and toxicological properties. Molecular docking analysis revealed that the molecules interact with proteins in critical sites for their activity. Using a virtual screening approach, a molecular docking study was performed for proteins encoded by genes that play important roles in cellular functions for carcinogenesis. Combining a systematic collection of public microarray data with a comparative meta-profiling, RT-qPCR, SBVS and molecular docking analysis provided a suitable approach for finding genes involved in GC and working with the corresponding proteins to search for new molecules with anticancer properties.

Controlling Hypertension through Education and Coaching in Kidney Disease (CHECK-D): protocol of a cluster randomised controlled trial.

INTRODUCTION: Chronic kidney disease (CKD) affects 30 million Americans. Early management focused on blood pressure (BP) control decreases cardiovascular morbidity and mortality. Less than 40% of patients with CKD achieve recommended BP targets due to many barriers. These barriers include a lack of understanding of the implications of their diagnosis and how to optimise their health.This cluster randomised control trial hypothesises that the combination of early primary care CKD education, and motivational interviewing (MI)-based health coach support, will improve patient behaviours aligned with BP control by increasing patient knowledge, self-efficacy and motivation. The results will aid in sustainable interventions for future patient-centric education and coaching support to improve quality and outcomes in patients with CKD stages 3-5. Outcomes in patients with CKD stages 3-5 receiving the intervention will be compared with similar patients within a control group. Continuous quality improvement (CQI) and systems methodologies will be used to optimise resource neutrality and leverage existing technology to support implementation and future dissemination. The innovative approach of this research focuses on the importance of a multidisciplinary team, including off-site patient coaching, that can intervene early in the CKD care continuum by supporting patients with education and coaching. METHODS AND ANALYSIS: We will test impact of BP control when clinician-delivered education is followed by 12 months of MI-based health coaching. We will compare outcomes in 350 patients with CKD stages 3-5 between intervention and control groups in primary care. CQI and systems methodologies will optimise education and coaching for future implementation and dissemination. ETHICS AND DISSEMINATION: This study was approved by the University of Michigan Institutional Review Boards (IRBMED) HUM00136011, HUM00150672 and SITE00000092 and the results of the study will be published on ClinicalTrials.gov, in peer-reviewed journals, as well as conference abstracts, posters and presentations. TRIAL REGISTRATION NUMBER: NCT04087798.

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis.

Background: Changes in brain connectivity occur in patients with multiple sclerosis (MS), even in patients under disease-modifying therapies. Using magnetic resonance imaging (MRI) to asses patients treated with disease-modifying therapies, such as natalizumab, can elucidate the mechanisms involved in clinical deterioration in MS. Objectives: To evaluate differences in resting-state functional connectivity among MS patients treated with natalizumab, MS patients not treated with natalizumab, and controls. Design: Single-center retrospective cross-sectional study. Methods: Twenty-three MS patients being treated with natalizumab were retrospectively compared with 23 MS patients who were naïve for natalizumab, and were using first-line medications (interferon-ß and/or glatiramer acetate), and 17 gender- and age-matched control subjects. The MS patient groups were also matched for time since diagnosis and hyperintense lesion volume on FLAIR. All participants underwent brain MRI using a 3 Tesla scanner. Independent component analysis and dual regression were used to identify resting-state functional connectivity using the FMRIB Software Library. Results: In comparison to controls, the MS patients treated with natalizumab presented decreased connectivity in the left orbitofrontal cortex, in the anterior cingulate and orbitofrontal cortex network. The patients not treated with natalizumab presented increased connectivity in the secondary visual, sensorimotor, and ventral attention networks in comparison to controls.Compared to patients treated with natalizumab, the patients not using natalizumab presented increased connectivity in the left Heschl's gyrus and in the right superior frontal gyrus in the ventral attention network. Conclusion: Differences in brain connectivity between MS patients not treated with natalizumab, healthy controls, and patients treated with natalizumab may be secondary to suboptimal neuronal compensation due to prior less efficient treatments, or due to a compensation in response to maladaptive plasticity.

Thiol-Michael Addition Microparticles: Their Synthesis, Characterization, and Uptake by Macrophages.

Polymeric microparticles are promising biomaterial platforms for targeting macrophages in the treatment of disease. This study investigates microparticles formed by a thiol-Michael addition step-growth polymerization reaction with tunable physiochemical properties and their uptake by macrophages. The hexafunctional thiol monomer dipentaerythritol hexa-3-mercaptopropionate (DPHMP) and tetrafunctional acrylate monomer di(trimethylolpropane) tetraacrylate (DTPTA) were reacted in a stepwise dispersion polymerization, achieving tunable monodisperse particles over a size range (1-10 µm) relevant for targeting macrophages. An off-stoichiometry thiol-acrylate reaction afforded facile secondary chemical functionalization to create particles with different chemical moieties. Uptake of the microparticles by RAW 264.7 macrophages was highly dependent on treatment time, particle size, and particle chemistry with amide, carboxyl, and thiol terminal chemistries. The amide-terminated particles were non-inflammatory, while the carboxyl- and thiol-terminated particles induced pro-inflammatory cytokine production in conjunction with particle phagocytosis. Finally, a lung-specific application was explored through time-dependent uptake of amide-terminated particles by human alveolar macrophages in vitro and mouse lungs in vivo without inducing inflammation. The findings demonstrate a promising microparticulate delivery vehicle that is cyto-compatible, is non-inflammatory, and exhibits high rates of uptake by macrophages.

Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Effect of different training frequencies on maximal strength performance and muscle hypertrophy in trained individuals-a within-subject design.

Several studies comparing resistance training (RT) frequencies may have been affected by the large between-subject variability. This study aimed to compare the changes in lower limbs maximal dynamic strength (1RM) and quadriceps femoris cross-sectional area (CSA) after a RT with different weekly frequencies in strength-trained individuals using a within-subject design. Twenty-four men participated in a 9-week RT program, being randomly divided into two conditions: resistance training with equalized total training volume (RTEV) and with unequalized total training volume (RTUV). The RT protocol used the unilateral leg press 45° exercise and each subject's lower limb executed one of the proposed frequencies (one and three times/week). All conditions effectively increased 1RM and CSA (p<0.001); however, no significant differences were observed in the values of 1RM (p = 0.454) and CSA (p = 0.310) between the RT frequencies in the RTEV and RTUV conditions. Therefore, RT performed three times a week showed similar increases in 1RM and CSA to the program performed once a week, regardless of training volume equalization. Nevertheless, when the higher RT frequency allowed the application of a greater TTV (i.e., RTUV), higher effect size (ES) values (0.51 and 0.63, 1RM and CSA, respectively) were observed for the adaptations.

The digiti quinti sign in hemiplegic migraine: An fMRI study.

BACKGROUND AND PURPOSE: The digiti quinti sign (DQS) consists of a wider angle between the fourth and fifth fingers (ANG) indicative of subtle hemiparesis that has been found interictally in hemiplegic migraine (HM), suggesting a permanent subtle motor dysfunction. The aim of this study was to find a possible cortical origin for the DQS using blood oxygen level dependent (BOLD) functional (f) MRI. METHODS: Eight HM patients and 13 controls entered the cross-sectional study. We examined hand dominance, performed handgrip tests with dynamometry, documented the DQS graphically in two consecutive sessions, and used BOLD-fMRI during a motor task specifically designed to measure the evoked activation in the motor cortex (M1). The brain activation at the symptomatic side was compared with the contralateral hemisphere and with both correspondent hemispheres in controls. RESULTS: Subjects had a normal neurological examination, except for DQS in all HM patients. The activation amplitude (beta values) and the cluster extension (mm3 ) of the activation area in M1 was smaller at the affected side. Besides, the cluster extension correlated negatively with the disease time span. The ANG was wider bilaterally in patients and the fMRI signals were reduced in the patient's group. CONCLUSION: The DQS, a relevant clinical finding in HM, indicates a disrupted cortical activation.

A Deep Learning-based Model for Detecting Abnormalities on Brain MR Images for Triaging: Preliminary Results from a Multisite Experience.

PURPOSE: To develop a deep learning model for detecting brain abnormalities on MR images. MATERIALS AND METHODS: In this retrospective study, a deep learning approach using T2-weighted fluid-attenuated inversion recovery images was developed to classify brain MRI findings as "likely normal" or "likely abnormal." A convolutional neural network model was trained on a large, heterogeneous dataset collected from two different continents and covering a broad panel of pathologic conditions, including neoplasms, hemorrhages, infarcts, and others. Three datasets were used. Dataset A consisted of 2839 patients, dataset B consisted of 6442 patients, and dataset C consisted of 1489 patients and was only used for testing. Datasets A and B were split into training, validation, and test sets. A total of three models were trained: model A (using only dataset A), model B (using only dataset B), and model A + B (using training datasets from A and B). All three models were tested on subsets from dataset A, dataset B, and dataset C separately. The evaluation was performed by using annotations based on the images, as well as labels based on the radiology reports. RESULTS: Model A trained on dataset A from one institution and tested on dataset C from another institution reached an F1 score of 0.72 (95% CI: 0.70, 0.74) and an area under the receiver operating characteristic curve of 0.78 (95% CI: 0.75, 0.80) when compared with findings from the radiology reports. CONCLUSION: The model shows relatively good performance for differentiating between likely normal and likely abnormal brain examination findings by using data from different institutions.Keywords: MR-Imaging, Head/Neck, Computer Applications-General (Informatics), Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms© RSNA, 2021Supplemental material is available for this article.

Habitual Caffeine Consumption Does Not Interfere With the Acute Caffeine Supplementation Effects on Strength Endurance and Jumping Performance in Trained Individuals.

The long-standing caffeine habituation paradigm was never investigated in strength endurance and jumping exercise performance through a straightforward methodology. The authors examined if habitual caffeine consumption would influence the caffeine ergogenic effects on strength endurance and jumping performance as well as perceptual responses. Thirty-six strength-trained individuals were mathematically allocated into tertiles according to their habitual caffeine consumption: low (20 ± 11 mg/day), moderate (88 ± 33 mg/day), and high consumers (281 ± 167 mg/day). Then, in a double-blind, crossover, counterbalanced fashion, they performed a countermovement vertical jump test and a strength endurance test either after caffeine (6 mg/kg) and placebo supplementation or after no supplementation (control). Perceptual responses such as ratings of perceived exertion and pain were measured at the termination of the exercises. Acute caffeine supplementation improved countermovement vertical jump performance (p = .001) and total repetitions (p = .004), regardless of caffeine habituation. Accordingly, analysis of absolute change from the control session showed that caffeine promoted a significantly greater improvement in both countermovement vertical jump performance (p = .004) and total repetitions (p = .0001) compared with placebo. Caffeine did not affect the rating of perceived exertion and pain in any exercise tests, irrespective of tertiles (for all comparisons, p > .05 for both measures). Caffeine side effects were similar in low, moderate, and high caffeine consumers. These results show that habitual caffeine consumption does not influence the potential of caffeine as an ergogenic aid in strength endurance and jumping exercise performance, thus challenging recommendations to withdraw from the habitual caffeine consumption before supplementing with caffeine.

Blood Flow Restriction Does Not Attenuate Short-Term Detraining-Induced Muscle Size and Strength Losses After Resistance Training With Blood Flow Restriction.

ABSTRACT: Teixeira, EL, de Salles Painelli, V, Silva-Batista, C, de Souza Barros, T, Longo, AR, Lasevicius, T, Schoenfeld, BJ, Aihara, AY, and de Almeida Peres, B. Blood flow restriction does not attenuate short-term detraining-induced muscle size and strength losses after resistance training with blood flow restriction. J Strength Cond Res 35(8): 2082-2088, 2021-After a short-term resistance training with blood flow restriction (BFR), we investigated the effects of 12 days of detraining (DET), without an exercise stimulus, on quadriceps cross-sectional area (QCSA) and muscle strength (1 repetition maximum [1RM]), with 1 leg receiving daily intermittent BFR during DET vs. the same nonexercise condition without BFR (CON) in the contralateral leg. Both subjects' legs were evaluated for QCSA and 1RM before (PRE) and after (POST) both legs being unilaterally submitted to 3 weeks (4 days per week) of low-load (3 sets of 15 repetitions, 30% 1RM) resistance training with BFR. The DET period started immediately after POST, where each leg was randomly submitted to a daily intermittent BFR protocol or CON, without any associated exercise stimulus. Quadriceps cross-sectional area and 1RM were reassessed after DET. Both legs at CON and BFR conditions increased QCSA (6.3 and 6.8%, respectively; both p < 0.0001) and 1RM (9.5 and 10.1%, respectively; both p < 0.05) from PRE to POST. Both legs at CON and BFR conditions reduced QCSA (-4.6 and 4.9%, respectively; both p < 0.0001) and 1RM (-9.0 and -8.2%, respectively; both p < 0.05) from POST to DET, with no significant differences between conditions (p > 0.05). We conclude that muscle strength and hypertrophy gains obtained in 3 weeks of resistance training with BFR are not maintained after 12 days of DET. Moreover, the application of BFR, without an associated exercise stimulus, does not attenuate such losses.

Does the Expectancy on the Static Stretching Effect Interfere With Strength-Endurance Performance?

ABSTRACT: Bertolaccini, AL, da Silva, AA, Teixeira, EL, Schoenfeld, BJ, and de Salles Painelli, V. Does the expectancy on the static stretching effect interfere with strength-endurance performance? J Strength Cond Res 35(9): 2439-2443, 2021-Static stretching (SS) may interfere with strength performance. Such interference, however, may be partially attributed to the subjects' or researcher's expectancy about the SS effects. We aimed to examine whether the manipulation of subjects' expectancy of SS on force production could influence strength-endurance during unilateral knee extension exercise. Eighteen strength-trained men were randomly divided into positively biased (PB; N = 9) or negatively biased (N = 9) groups on the possible effects of SS on performance. Subjects' total number of repetitions and total volume of exercise were assessed during strength-endurance tests (4 sets performed to failure at 70% of 1 repetition maximum) performed under 2 different conditions on separate days: Control-no stretching (CON); or SS. Static stretching consisted of 3 sets of 3 stretching exercises, lasting 30 seconds each. Data were analyzed using mixed models. Neither the total number of repetitions nor the total volume was significantly different between the CON and SS conditions, nor for type of bias (all p > 0.05). However, the number of repetitions in the last set of exercise was greater during SS compared with CON for the PB group (p = 0.01). Although previous negative or positive information about SS did not interfere with the total number of repetitions and total volume of exercise, previous positive information about SS improved performance in the last set of exercise. Expectancy therefore may have played a partial role influencing strength-endurance in previous studies.

Dietary Strategies of Modern Bodybuilders During Different Phases of the Competitive Cycle.

ABSTRACT: Lenzi, JL, Teixeira, EL, de Jesus, G, Schoenfeld, BJ, and de Salles Painelli, V. Dietary strategies of modern bodybuilders during different phases of the competitive cycle. J Strength Cond Res 35(9): 2546-2551, 2021-Bodybuilders have used a wide array of nutritional strategies over the years. However, most information on the topic is anecdotal, with limited research about the nutritional habits of modern bodybuilders, especially those from new categories. Accordingly, we sought to compare the dietary routines of bodybuilders from the Men's Physique category during "bulking" and "cutting" phases, while attempting to identify the rationale underpinning these practices. Sixteen experienced male bodybuilding competitors were interviewed during bulking (10-12 weeks before competition) and cutting (1 week before competition) phases, wherein we quantified energy and nutrient intake and determined their rationale and sources of education. Dietary analysis revealed a low carbohydrate intake during bulking, with a further decrease (at p < 0.05) during cutting. A similar decrease (at p < 0.05) from bulking to cutting was shown in the intake of most macronutrients and micronutrients, although intake of protein and almost all the micronutrients was well above the recommendation throughout the competitive cycle. Most of the consumed supplements can be deemed unnecessary or without scientific support. Most athletes reported self-managing their diet and supplement program, without the assistance of nutrition professionals. As such, some of their professed nutritional habits obtained during interviewers were not consistent with the food diary information. Although some dietary strategies used by bodybuilders in the Men's Physique category are consistent with evidence-based practice, most can be considered extreme and lack scientific support. The source of education may help to explain their decision-making.

Posterior cingulate gyri metabolic alterations in HIV-positive patients with and without memory deficits.

OBJECTIVE: We aimed to evaluate whether human immunodeficiency virus (HIV)-positive patients with and without clinically significant memory deficits and healthy control participants differ on in vivo hydrogen-1 magnetic resonance spectroscopy (H-MRS) in the posterior cingulate gyri. MATERIALS AND METHODS: In total, 21 HIV-positive patients with memory deficit (HIV+wMD) were compared with 15 HIV-positive patients without memory deficit (HIV+wOMD) and 22 sex-, age-, and education-matched control participants. Memory impairments were classified based on the participants' performance on the Rey Auditory Verbal Learning Test. Short echo time (30 ms), single-voxel H-MRS was performed using a 1.5-T magnetic resonance scanner. RESULTS: The HIV+wMD and HIV+wOMD groups had higher choline/creatine ratio in the posterior cingulate gyri than the control group. There were no significant metabolite ratio differences between the HIV+wMD and HIV+wOMD groups. CONCLUSION: HIV-positive patients with and without memory deficits had significantly higher choline/creatine ratios than controls in the posterior cingulate gyri, which may reflect cerebral inflammation, altered cell membrane metabolism, microgliosis, and/or astrocytosis.

OBJETIVO: Nós avaliamos se os pacientes HIV-positivos com e sem déficits de memória clinicamente significativos e controles saudáveis diferem na espectroscopia de prótons do giro do cíngulo posterior, por ressonância magnética (RM) cerebral. MATERIAIS E MÉTODOS: Vinte e um pacientes HIV-positivos com déficit de memória foram comparados com 15 pacientes HIV-positivos sem déficit de memória e 22 controles, pareados por sexo, idade e escolaridade. As deficiências de memória foram classificadas por meio do desempenho no Teste de Aprendizagem Auditivo-Verbal de Rey. A espectroscopia de prótons foi realizada com tempo de eco curto (30 ms), por voxel único, no giro do cíngulo posterior, utilizando aparelho de RM de 1,5 T. RESULTADOS: Os pacientes HIV-positivos com e sem déficit de memória apresentaram aumento da relação colina/creatina no giro do cíngulo posterior, comparados aos controles. Não houve diferenças significativas nas relações metabólicas no grupo HIV-positivo com déficit de memória, em relação ao grupo de pacientes HIV-positivo sem déficit. CONCLUSÃO: Pacientes HIV-positivos com e sem déficits de memória apresentaram relações colina/creatina significativamente aumentadas em relação aos controles, no giro do cíngulo posterior, o que pode refletir inflamação cerebral, alteração do metabolismo da membrana celular, microgliose e/ou astrocitose.

Posterior cingulate gyri metabolic alterations in HIV-positive patients with and without memory deficits / Alterações metabólicas no giro do cíngulo posterior em pacientes HIV-positivos com e sem déficit de memória

Abstract Objective: We aimed to evaluate whether human immunodeficiency virus (HIV)-positive patients with and without clinically significant memory deficits and healthy control participants differ on in vivo hydrogen-1 magnetic resonance spectroscopy (H-MRS) in the posterior cingulate gyri. Materials and Methods: In total, 21 HIV-positive patients with memory deficit (HIV+wMD) were compared with 15 HIV-positive patients without memory deficit (HIV+wOMD) and 22 sex-, age-, and education-matched control participants. Memory impairments were classified based on the participants' performance on the Rey Auditory Verbal Learning Test. Short echo time (30 ms), single-voxel H-MRS was performed using a 1.5-T magnetic resonance scanner. Results: The HIV+wMD and HIV+wOMD groups had higher choline/creatine ratio in the posterior cingulate gyri than the control group. There were no significant metabolite ratio differences between the HIV+wMD and HIV+wOMD groups. Conclusion: HIV-positive patients with and without memory deficits had significantly higher choline/creatine ratios than controls in the posterior cingulate gyri, which may reflect cerebral inflammation, altered cell membrane metabolism, microgliosis, and/or astrocytosis.

Resumo Objetivo: Nós avaliamos se os pacientes HIV-positivos com e sem déficits de memória clinicamente significativos e controles saudáveis diferem na espectroscopia de prótons do giro do cíngulo posterior, por ressonância magnética (RM) cerebral. Materiais e Métodos: Vinte e um pacientes HIV-positivos com déficit de memória foram comparados com 15 pacientes HIV-positivos sem déficit de memória e 22 controles, pareados por sexo, idade e escolaridade. As deficiências de memória foram classificadas por meio do desempenho no Teste de Aprendizagem Auditivo-Verbal de Rey. A espectroscopia de prótons foi realizada com tempo de eco curto (30 ms), por voxel único, no giro do cíngulo posterior, utilizando aparelho de RM de 1,5 T. Resultados: Os pacientes HIV-positivos com e sem déficit de memória apresentaram aumento da relação colina/creatina no giro do cíngulo posterior, comparados aos controles. Não houve diferenças significativas nas relações metabólicas no grupo HIV-positivo com déficit de memória, em relação ao grupo de pacientes HIV-positivo sem déficit. Conclusão: Pacientes HIV-positivos com e sem déficits de memória apresentaram relações colina/creatina significativamente aumentadas em relação aos controles, no giro do cíngulo posterior, o que pode refletir inflamação cerebral, alteração do metabolismo da membrana celular, microgliose e/ou astrocitose.

Progression of heart failure is attenuated by antioxidant therapy with N-acetylcysteine in myocardial infarcted female rats.

This study investigated the therapeutic potential of N-acetylcysteine (NAC) in the treatment of heart failure in female rats. Myocardial infarcted (MI) rats were given NAC (250 mg/kg/day p.o.) during 28 days after surgery (MI + NAC) or vehicle (MI + Placebo), and sham-operated rats received the same treatments (Sham + NAC and Sham + Placebo). Electrocardiographic and echocardiographic analyses were performed in the last week of treatment. Cardiac mRNA levels of types I and II superoxide dismutase (SOD), catalase, types I and III glutathione peroxidase (GPX), nerve growth factor (NGF), ß1-adrenergic receptor (ß1ADR), and type 2 muscarinic receptor (M2R) were assessed. Cardiac levels NADPH oxidase (NOX) activity, total content of reduced thiols, and SOD, GPX, and catalase activity were assessed. Compared to MI + Placebo group, MI + NAC group exhibited decreased NOX activity, increased content of reduced thiols, increased GPX activity, and normalized GPX III mRNA levels (p < 0.05). Heart and lung weights, left ventricular (LV) end-diastolic volume and left atrium/aorta ratio were decreased, while LV posterior wall thickness and ejection fraction were increased in MI + NAC group versus MI + Placebo rats (p < 0.05). Power density of low frequency band was decreased, while power density of high frequency and the root mean square of the successive differences were increased in MI + NAC rats versus MI + Placebo (p < 0.05). These findings indicate that NAC promotes therapeutic effects in the progression of MI-induced heart failure in female rats.

Anabolic steroid excess promotes hydroelectrolytic and autonomic imbalance in adult male rats: Is it enough to alter blood pressure?

AIM: The present study investigated the effects of anabolic steroid (AS) excess on blood pressure regulation. METHODS: Male Wistar rats were treated with nandrolone decanoate (AS) or vehicle (CTL) for 8 or 10 weeks. Saline (1.8%) and water intake were measured in metabolic cages. Urinary volume, osmolarity, Na+ and K+ concentrations, and plasma osmolarity were measured. The autonomic balance was estimated by heart rate variability at baseline or after icv injection of losartan. Cardiac function was assessed by echocardiography and ex vivo recordings. Myocardial collagen deposition was evaluated by Picrosirius-Red staining. Vascular reactivity and wall thickness were investigated in aortic sections. Blood pressure (BP) was assessed by tail-cuff plethysmography. Angiotensin II type I receptor (AT1R), renin, and mineralocorticoid receptor (MR) mRNA expression was measured in the kidneys and whole hypothalamus. RESULTS: AS group exhibited decreased urinary volume and Na+ concentration, while urinary K+ concentration, plasma osmolarity, and renal AT1R and renin mRNA levels were increased compared to CTL (p < 0.05). Water intake was increased, and saline intake was decreased in the AS group (p < 0.01). AS group exhibited increased low-frequency/high-frequency-ratio, while it was decreased by icv injection of losartan (p < 0.05) compared to baseline. Neither cardiac function nor vascular reactivity/morphology was affected by AS excess (p > 0.05). Ultimately, BP levels were not altered by AS excess (p > 0.05). CONCLUSION: AS excess promoted hydroelectrolytic and autonomic imbalance but did not alter vascular or cardiac function/morphology.

Nitric oxide/cGMP signaling pathway and potassium channels contribute to hypotensive effects of nothofagin.

BACKGROUND: Nothofagin is a mono-C-glycoside of 4,2',4',6'-tetrahydroxy-dihydrochalcone that is commonly found in Aspalathus linearis, Nothofagus fusca, and Leandra dasytricha. A wide range of biological effects has been attributed to nothofagin, including antioxidant, diuretic, renoprotective, antiplatelet, and antithrombotic effects. Although nothofagin is pharmacologically active, its effects on blood pressure remain unknown. In the present study, we investigated whether nothofagin causes acute and prolonged hypotension in male Wistar rats, and we investigated the molecular mechanisms that underlie these hemodynamic effects. METHODS: Hypotensive effects of nothofagin (0.3, 1, and 3 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. Using pharmacological antagonists and inhibitors, we explored the involvement of the prostaglandin/cyclic adenosine monophosphate and nitric oxide/cyclic guanosine monophosphate pathways and K+ channels in nothofagin-induced hypotension. RESULTS: Acute and prolonged nothofagin administration significantly decreased systolic blood pressure and mean arterial pressure in Wistar rats. Pretreatment with N(G)-nitro-L-arginine methyl ester, methylene blue, and tetraethylammonium prevented the hypotensive effect of nothofagin. CONCLUSIONS: These results show that nothofagin induces a hypotensive response in Wistar rats, and this effect depends on K+ channel opening in smooth muscle cells through nitric oxide signaling.