Mesenchymal stem cell transplantation: Systematic review, meta-analysis and clinical applications for acute kidney injury and chronic kidney disease in dogs and cats.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are diseases which affect the urinary tract characterized by the loss of renal function. Their therapy requires different therapeutic goals. Mesenchymal stem cells (MSC) transplantation has spread over the years as a treatment for many diseases. In the urinary tract, studies report anti-inflammatory, antiapoptotic, antifibrotic, antioxidant and angiogenic effects. This work reports the results of a meta-analysis about the effects of the MSC application in serum levels of creatinine in dogs and cats with AKI and CKD. The work followed PRISMA guidelines. Data were screened, selected, and extracted with characteristics about the studies. The kinds of injury were classified according to their identification and the risk of bias was calculated by the system SYRCLE. The results of each group were combined by the inverse variance method. The heterogeneity was evaluated by the I2 test. For the mean of creatinine, a meta-analysis was performed according to the study group and number of applications and separately for the control and treatment groups according to the kind of injury, dose, application route, and moment. At all, 4742 articles were found. Of these, 40 were selected for eligibility, 16 underwent qualitative analysis and 9 to the quantitative. The results denote advantage to the group treated with MSC over placebo. A statistical difference was observed both in combined analysis and in the subgroups division. However, a high heterogeneity was found, which indicates considerable variation between the studies, which indicates caution in generalize the results.

Standardized phase angle: relationship with functionality, muscle mass and postoperative outcomes in surgical cancer patients.

To evaluate the association of standardized phase angle (SPA) with nutritional status, functional parameters, and postoperative outcomes in surgical cancer patients. This prospective study includes 59 cancer patients from Pelotas (Brazil) admitted for elective cancer surgery. We obtained the phase angle through Bioelectrical Impedance Analysis (BIA) and standardized it according to the population's reference values. We estimated the muscle mass using BIA for later calculation of the Skeletal Muscle Index (SMI) and performed handgrip strength (HGS) and gait speed (GS) tests. We used the Patient-Generated Subjective Global Assessment (PG-SGA) to assess the nutritional status. Postoperative complications and duration of hospital stay were evaluated as the outcomes. The prevalence of malnutrition in the sample was 28.8%, according to ASG-PPP. SPA was statistically lower in patients with malnutrition, with lower HGS and reduced GS. For postoperative outcomes, patients with severe complications and those with prolonged hospitalization also had lower SPA values. The greater the number of functional alterations in patients, the lower the SPA value, mainly when associated with reduced muscle mass assessed by BIA, suggesting that muscle mass reduction plays an important role in the association between functional alterations and phase angle in patients with cancer. According to the parameters used in this study, low SPA value was associated with impaired nutritional and functional status and negative outcomes in the analyzed sample.

Strength training improves heart function, collagen and strength in rats with heart failure.

BACKGROUND/OBJECTIVES: Myocardial infarction (MI) frequently leads to cardiac remodeling and failure with impaired life quality, playing an important role in cardiovascular deaths. Although physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases, the effects of strength training (ST) on the structural and functional aspects of cardiac remodeling need to be further documented. In this study, we aimed to investigate the role of a linear block ST protocol in the rat model of MI. METHODS AND RESULTS: After 6 weeks of MI induction or sham surgery, male adult rats performed ST for the following 12 weeks. The ladder-based ST program was organized in three mesocycles of 4 weeks, with one load increment for each block according to the maximal carrying load test. After 12 weeks, the infarcted-trained rats exhibited an increase in performance, associated with reduced cardiac hypertrophy and pulmonary congestion compared with the untrained group. Despite not changing MI size, the ST program partially prevented cardiac dilatation and ventricular dysfunction assessed by echocardiography and hemodynamics, and interstitial fibrosis evaluated by histology. In addition, isolated cardiac muscles from infarcted-trained rats had improved contractility parameters in a steady state, and in response to calcium or stimuli pauses. CONCLUSIONS: The ST in infarcted rats increased the capacity to carry mass, associated with attenuation of cardiac remodeling and pulmonary congestion with improving cardiac function that could be attributed, at least in part, to the improvement of myocardial contractility.

Effects of dipeptidyl peptidase 4 inhibition on the endothelial control of the vascular tone.

Dipeptidyl peptidase 4 (DPP4) is a serine protease known to cleave incretin hormones, which stimulate insulin secretion after food intake, a fact that supported the development of its inhibitors (DPP4i or gliptins) for the treatment of type 2 diabetes mellitus. In addition to their glucose-lowering effects, DPP4i show benefits for the cardiovascular system that could be related, at least in part, to their protective action on vascular endothelium. DPP4i have been associated with the reversal of endothelial dysfunction, an important predictor of cardiovascular events and a hallmark of diseases such as atherosclerosis, diabetes mellitus, hypertension, and heart failure. In animal models of these diseases, DPP4i increase nitric oxide bioavailability and limits oxidative stress, thereby improving the endothelium-dependent relaxation. Similar effects on flow-mediated dilation and attenuation of endothelial dysfunction have also been noted in human studies, suggesting a value for gliptins in the clinical scenario, despite the variability of the results regarding the DPP4i used, treatment duration, and presence of comorbidities. In this mini-review, we discuss the advances in our comprehension of the DPP4i effects on endothelial regulation of vascular tone. Understanding the role of DPP4 and its involvement in the signaling mechanisms leading to endothelial dysfunction will pave the way for a broader use of DPP4i in conditions that endothelial dysfunction is a pivotal pathophysiological player.

Experimental charge density and topological analysis of tetraaquabis(hydrogenmaleato)nickel(II): a comparison with Hirshfeld atom refinement.

Experimental charge density analysis is conducted on the coordination compound tetraaquabis(hydrogenmaleato)nickel(II), which exhibits a short intramolecular hydrogen bond. Through topological analysis, the nature of Ni-O bonds is concluded to be intermediate between ionic and covalent, but mainly presenting an ionic character, while the short hydrogen bond is classified as covalent in nature. The compound was also analysed after Hirshfeld atom refinement performed using NoSpherA2. A topological analysis was conducted on the molecular wavefunction and the results are compared with those obtained from experiment. In general, there is good agreement between the refinements, and the chemical bonds involving H atoms are in better agreement with what is expected from neutron data after HAR than they are after multipole refinement.

Effects of home confinement on physical activity, nutrition, and sleep quality during the COVID-19 outbreak in amateur and elite athletes.

Introduction: Despite the progress in the management of the pandemic caused by COVID-19, it is necessary to continue exploring and explaining how this situation affected the athlete population around the world to improve their circumstances and reduce the negative impact of changes in their lifestyle conditions that were necessitated due to the pandemic. The aim of this study was to analyze the moderating influence of physical activity (PA) and dietary habits on the impact of the COVID-19 pandemic experience on sleep quality in elite and amateur athletes. Materials and methods: A total of 1,420 elite (40.1%) and amateur (59.9%) athletes (41% women; 59% men) from 14 different countries participated in a cross-sectional design study. Data were collected using a battery of questionnaires that identified sociodemographic data, sleep quality index, PA levels, dietary habits, and the athletes' perception of their experience during the COVID-19 pandemic. Means and standard deviations were calculated for each variable. The analysis of variances and the correlation between variables were carried out with non-parametric statistics. A simple moderation effect was calculated to analyze the interaction between PA or dietary habits on the perception of the COVID-19 experience effect on sleep quality in elite and amateur athletes. Results: The PA level of elite athletes was higher than amateur athletes during COVID-19 (p < 0.001). However, the PA level of both categories of athletes was lower during COVID-19 than pre-COVID-19 (p < 0.01). In addition, amateurs had a higher diet quality than elite athletes during the pandemic (p = 0.014). The perception of the COVID-19 experience as controllable was significantly higher (p = 0.020) among elite athletes. In addition, two moderating effects had significant interactions. For amateur athletes, the PA level moderated the effect of controllable COVID-19 experience on sleep quality [F (3,777) = 3.05; p = 0.028], while for elite athletes, the same effect was moderated by dietary habits [F (3,506) = 4.47, p = 0.004]. Conclusion: Elite athletes had different lifestyle behaviors compared to amateurs during the COVID-19 lockdown. Furthermore, the relevance of maintaining high levels of PA for amateurs and good quality dietary habits by elite athletes was noted by the moderating effect that both variables had on the influence of the controllable experience during the COVID-19 pandemic on sleep quality.

Chemical similarity of dialkyl carbonates and carbon dioxide opens an avenue for novel greenhouse gas scavengers: cheap recycling and low volatility via experiments and simulations.

Global warming linked to the industrial emissions of greenhouse gases may be the end of mankind unless it is adequately and timely handled. To prevent irreversible changes to the climate of the Earth, numerous research groups are striving to develop robust CO2 sorbents. Dialkyl carbonates (DACs) and CO2 exhibit obvious chemical similarities in their structure and properties. The degrees of oxidation of all atoms composing DACs and CO2 are identical resulting in very similar nucleophilicities and electrophilicities of all interaction centers. While both compounds possess relatively high partial atomic charges on their polar moieties, the molecular geometries prevent tight binding of the head groups. The computed DAC-DAC binding energies are ∼40 kJ mol-1, whereas the effect of the alkyl chain length is marginal. The phase transition points and shear viscosities of DACs are very low. We herein hypothesize and numerically rationalize that DACs represent noteworthy physical sorbents for CO2 thanks to the similar sorbent-CO2 and sorbent-sorbent interaction energies. By reporting in silico-derived sorption thermodynamics at various conditions, spectral and structural properties, and experimentally derived CO2 capacities and recyclabilities, we highlight the mutual affinity of DACs and CO2. Indeed, the experimentally determined CO2 sorption capacity of 0.88 mol% (diethyl carbonate) at 278.15 K and 30 bar is competitive. The unprecedentedly low DAC-CO2 binding energies, ∼14 kJ mol-1, suggest a low-cost desorption process and outstanding recyclability of the sorbent. We also note that DACs possessing long alkyl chains (butyl, hexyl, octyl) exhibit negligible volatilities, while preserving the liquid aggregate state over a practically important temperature range. The reported results may foster the development of a new class of CO2 scavengers with possibly quite peculiar characteristics.

Distributed functional-group polarizabilities in polypeptides and peptide clusters toward accurate prediction of electro-optical properties of biomacromolecules.

CONTEXT: Aiming at accurately predicting electro-optical properties of biomolecules, this work presents distributed atomic and functional-group polarizability tensors for a series of polypeptides and peptide clusters constructed from glycine and its residuals. By partitioning the electron density using the quantum theory of atoms in molecules, we demonstrated a very good transferability of the group polarizabilities. We were able to identify and extract the most efficient functional groups capable of generating the largest electrical susceptibility in condensed phases. Both the isotropic polarizability and its anisotropy were used to understand the way functional groups act as sources of linear optical responses, how they interact with each other reinforcing the macroscopic optical behavior within the material, and how covalent bonds and non-covalent interactions, such as hydrogen bonds, determine refractive indices and birefringence. Particular attention is devoted to the peptide bonds as they provide links to build biomacromolecules or polymers. An adequate quantum-mechanical treatment of at least the first interaction sphere of a given functional group is required to properly describe the effects of mutual polarization, but we identified optimum cluster size and shape to better estimate polarizabilities and dipole moments of larger molecules or molecular aggregates from the knowledge of the electron density of a central molecule or amino acid residual that is representative of the bulk. The strategy outlined here is a fast yet effective tool for estimating the optical properties of proteins but could eventually find application in the rational design of optical organic materials as well. METHODS: Electronic-structure calculations were performed on the Gaussin16 program at the DFT level using the CAMB3LYP functional and the double-ζ quality Dunning basis set aug-cc-pVDZ. Electron density partitioning followed the concepts of the Quantum Theory of Atoms and Molecules (QTAIM) and was performed using the AIMAll program. The locally developed Polaber routine was applied to calculate dipole moment vectors and polarizability tensors. It was amended to include the effects of the local field on a given central molecule by means of a modified Atom-Dipole Interaction Model (ADIM).

Benchmark of a functional-group database for distributed polarizability and dipole moment in biomolecules.

The extraction of functional-group properties in condensed phases is very useful for predicting material behaviors, including those of biomaterials. For this reason, computational approaches based on partitioning schemes have been developed aiming at rapidly and accurately estimating properties from chemically meaningful building blocks. A comprehensive database of group polarizabilities and dipole moments is useful not only to predict the optical properties of biomacromolecules but also to improve molecular force fields focused on simulating biochemical processes. In this work we benchmark a database of distributed polarizabilities and dipole moments for functional groups extracted from a series of polypeptides. This allows reconstruction of a variety of relevant chemical environments. The accuracy of our database was tested to predict the electro-optical properties of larger peptides and also simpler amino acids for which density functional theory calculations at the M06-HF/aug-cc-pVDZ level of theory was chosen as the reference. This approach is reasonably accurate for the diagonal components of the polarizability tensor, with errors not larger than 15-20%. The anisotropy of the polarizability is predicted with smaller efficacy though. Solvent effects were included explicitly by surrounding the database entries by a box of water molecules whose distribution was optimized using the CHARMM force field.

Avaliação do uso de álbum seriado sobre amamentação como estratégia de intervenção educativa no puerpério / Evaluation of the use of a flipchart about breastfeeding as an educational intervention strategy in the puerperium

Introdução: A amamentação é um ato que vai além de nutrir a criança. A implementação de tecnologias educacionais pode favorecer a promoção do aleitamento materno. Objetivo: Avaliar o uso de álbum seriado sobre amamentação com estratégia de intervenção educativa no puerpério imediato entre puérperas de maternidade pública de acordo com o perfil sociodemográfico e obstétrico. Materiais e métodos: Estudo quase-experimental de modelo pré e pós-teste com único grupo, realizado entre novembro de 2019 e março de 2020. Dados coletados através da escala de autoeficácia em aleitamento materno Breastfeeding Self-Efficacy Scale ­ short form. Avaliou-se a quantidade de mulheres em alta autoeficácia antes e depois da intervenção. Por não apresentarem normalidade e/ou homogeneidade de variância, foram realizados testes não paramétricos de Kruskal-Wallis com post-hoc de Nemenyi. Resultados: Os resultados demonstraram que houve aumento da autoeficácia após a intervenção, sobretudo em puérperas menores de 18 anos, com Ensino Fundamental, donas de casa, com menos de seis consultas, as orientadas sobre amamentação no pré-natal e as que não amamentaram anteriormente. Discussão: O perfil sociodemográfico das genitoras pode representar influência sobre a autoeficácia na amamentação. Conclusão: a tecnologia educativa foi eficaz no aumento da autoeficácia materna em amamentar no puerpério imediato.

Introduction: Breastfeeding is an act that goes beyond nourishing the child. The implementation of educational technologies can favor the promotion of breastfeeding. Objective: To evaluate the use of a flipchart about breastfeeding as an educational intervention strategy in the immediate postpartum period among mothers in a public maternity hospital according to their sociodemographic and obstetric profile. Materials and Methods: Quasi-experimental study of a pre- and post-test model with a single group, carried out between November 2019 and March 2020. Data collected through the Breastfeeding Self-Efficacy Scale ­ short form. The number of women with high self-efficacy before and after the intervention was evaluated. As they did not show normality and/or homogeneity of variance, non-parametric Kruskal-Wallis tests with post-hoc Nemenyi tests were performed. Results: The results showed that there was an increase in self-efficacy after the intervention, especially in puerperal women under 18 years of age, with Elementary Education, housewives, with less than six consultations, those oriented about breastfeeding during prenatal care and those who had not previously breastfed. Discussion: The sociodemographic profile of mothers may influence self-efficacy in breastfeeding. Conclusion: educational technology was effective in increasing maternal self-efficacy in breastfeeding in the immediate puerperium.

Introducción: La lactancia materna es un acto que va más allá de nutrir al niño. La implementación de tecnologías educativas puede favorecer la promoción de la lactancia materna. Objetivo: Evaluar el uso de un rotafolio sobre lactancia materna como estrategia de intervención educativa en el puerperio inmediato en puérperas de una maternidad pública según su perfil sociodemográfico y obstétrico. Materiales y Métodos: Estudio cuasiexperimental de un modelo de pre y post test con un solo grupo, realizado entre noviembre de 2019 y marzo de 2020. Datos recolectados a través de la Escala de Autoeficacia en Lactancia Materna ­ forma corta. Se evaluó el número de mujeres con alta autoeficacia antes y después de la intervención. Debido a que no mostraron normalidad y/u homogeneidad de varianza, se realizaron pruebas no paramétricas de Kruskal-Wallis con pruebas post-hoc de Nemenyi. Resultados: Los resultados mostraron que hubo un aumento en la autoeficacia después de la intervención, especialmente en las puérperas menores de 18 años, con Educación Primaria, amas de casa, con menos de seis consultas, las orientadas sobre lactancia materna durante el prenatal y las que tenían no amamantado previamente. Discusión: El perfil sociodemográfico de las madres puede influir en la autoeficacia en la lactancia. Conclusión: la tecnología educativa fue efectiva para aumentar la autoeficacia materna en la lactancia materna en el puerperio inmediato.

Hematological changes in human lymphotropic-T virus type 1 carriers.

The human T-lymphotropic virus type 1 (HTLV-1), isolated in 1980, causes T-cell leukemia/lymphoma in adulthood, a type of lymphoproliferative disease, and chronic HTLV-1-associated myelopathy, a disease that causes paralysis of the lower limbs, which occur in about 5% of cases in this viral infection. This study aimed to establish the hematological profile of patients with HTLV-1 infection in Belém do Pará, describing the hematological parameters under study, estimating the frequency of lymphocytic atypical, and associating the hematological profile with diseases and symptoms. Hematologic data from 202 individuals were analyzed, including 87 HTLV-1 infected individuals and 115 non-HTLV-1 infected individuals as a control group, composed, at a great part, of relatives of the infected. The seroprevalence of HTLV-1 infection was observed in 71.3% of female individuals, with predominance in the group older than 50 years (44.8%). The analysis of hematological parameters showed a significant difference in the counts of the segmented cells (p = 0.0303) and eosinophils (p = 0.0092) in HTLV-1 carriers. Lymphocytic atypical was a finding present only in HTLV-1 carriers (p = 0.0001). There was no high frequency in the leukocyte counts of those infected by HTLV-1 not among them concerning a significant increase or decrease. It is concluded that HTLV-1 infection is prominent in women over 50 years old. The hematological profile of those infected shows a reduction of segmented cells, an increase of eosinophils, and the presence of atypical lymphocytes. The hematological profile of the HTLV-1 carrier should always be evaluated to identify early some diseases associated with the infection.

Physical frailty in patients with systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a chronic disease characterized by autoimmunity, vasculopathy and fibrosis of several organs, such as skin, lungs, and heart. During the disease course, patients with SSc are prone to accumulating multiple organ damage and increasing their vulnerability to adverse outcomes. This increased vulnerability to adverse outcomes when exposed to a stressor among people of the same age is known as frailty. One of the most used definitions of frailty is the physical frailty phenotype (PFP), including 5 components: unintentional weight loss, exhaustion, muscle weakness, slow walking speed, and low physical activity. There is scarce data about frailty in patients with SSc. OBJECTIVES: To determine the prevalence and clinical profile of PFP in a sample of patients with SSc. To investigate the diagnostic accuracy of the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) scale, Edmonton frailty scale (EFS) and Short Physical Performance Battery (SPPB) using the PFP as the reference standard. METHODS: Cross-sectional study including 94 patients with SSc according to the 2013 ACR-EULAR classification criteria or the criteria suggested by Le Roy and Medsger for early disease. Gastrointestinal symptoms were assessed by the UCLA GIT 2.0 questionnaire, malnutrition was defined according to European Society of Clinical Nutrition and Metabolism (ESPEN) recommendations, and physical performance was assessed by SPPB. PFP assessment was according to the original definition, except for physical activity domain, assessed with the International Physical Activity Questionnaire (IPAQ). FRAIL scale and EFS were also applied to the same individuals. For diagnostic assessment of FRAIL, EFS and SPPB, we estimated the area under the receiver operating characteristic curve (AUC), considering PFP as the reference standard and dichotomizing the results in frail vs. non-frail. RESULTS: According to PFP, 33 patients (35.1%) were considered frail and 53 patients (56.4%) pre-frail. According to FRAIL scale, 27 patients (28.7%) were considered frail and 53 patients (56.4%) pre-frail. According to EFS, 28 patients (29.7%) were classified as vulnerable and 15 (15.9%) as frail: mild in 8 (8.5%), moderate in 5 (5.3%) and severe in 2 (2.1%). According to SPPB, 19 patients (20.2%) were considered frail. The AUC against PFP was: 0.829 (95% CI 0.743-0.916) for FRAIL scale, 0.859 (95% CI 0.784-0.934) for EFS and 0.791 (95% CI 0.697-0.885) for SPPB. The PFP was associated with current use of glucocorticoids (p=0.011), UCLA GIT 2.0 score (p=0.001), HAQ (p<0.0001), patient and physician-assigned VAS (p<0.0001, both), malnutrition (p=0.007), hospitalizations in the past year (p=0.008) and dependence on BADL and IADL (p=0.027 and p<0.0001, respectively). The PFP was not associated with gender (p=0.679), age (p=0.303), disease duration (p=0.504), Rodnan skin score (p=0.918), diffuse subtype (p=0.116), polypharmacy (p=845) and sarcopenia (p=0.328). CONCLUSION: Frailty is prevalent in patients with long-standing SSc and is associated with disability, limitations in daily activities and hospitalizations in the past year. Also, malnutrition and more severe gastrointestinal symptoms were more common in frail patients. Both FRAIL scale and EFS showed excellent diagnostic accuracy against PFP as the reference standard, however the FRAIL scale presents a higher sensitivity and seems to be more feasible and practical than EFS and SPPB in clinical practice.

High prevalence of sexual infection by human papillomavirus and Chlamydia trachomatis in sexually-active women from a large city in the Amazon region of Brazil.

BACKGROUND: The Human Papillomavirus (HPV) and Chlamydia trachomatis are the most prevalent Sexually Transmitted Infections (STIs) worldwide, and are associated cervical cancer and pelvic inflammatory disease, respectively. However, 80% of women testing positive are asymptomatic. In the Amazon region, young women, in particular, are widely exposed to the infections and their consequences. OBJECTIVES: Determine the prevalence of sexual infection by HPV and C. trachomatis in young, sexually-active women treated at a university health program in a large city of the Brazilian Amazon region. METHODS: We amplified the L1 gene of HPV. We amplified ompA gene of C. trachomatis by nested PCR, and the study participants filled in a questionnaire on their social, epidemiological, and reproductive health characteristics. The data were analyzed using the Odds Ratio, to evaluate the degree of association of these variables with the observed infections. RESULTS: The prevalence of infection by HPV was 15.5% (47/303). This infection was recorded in 32.2% of the women of less than 25 years of age (OR:3.02 [CI95%] = 1.32-6.92; p = 0.014), 17.9% of the single women (OR: 2.41 [CI95%] = 1.22-4.75; p = 0.014), 23.8% of the women that reported having first sexual intercourse at less than 15 years of age (OR: 2.22 [CI95%] = 1.16-4.23; p = 0.021), 20% of those that reported having had more than one sexual partner during their lifetime (OR: 3.83 [CI95%] = 1.56-9.37; p = 0.003), and in 28.3% that use oral contraceptives (CI95% = 1.33-5.43; p = 0.008). The prevalence of sexual infection by C. trachomatis was 4.6% (14/303), and this bacterium was present in 16.1% of the young women of less than 25 years of age (OR: 2.86 [CI95%] = 1.33-5.43; p = 0.008). CONCLUSIONS: We found a high prevalence of HPV in young, unmarried women who started their sex lives early, who had several sexual partners in their lives and who used oral contraceptives. The prevalence of C. trachomatis was high only in young women. Our data are in accordance with other studies in Brazil and in the world and may serve to base the formulation of diagnostic and screening measures for these infections in women in the Amazon.

Iron overload, oxidative stress and vascular dysfunction: Evidences from clinical studies and animal models.

Although iron is a metal involved in many vital processes due to its redox capacity, body iron overloads lead to tissue damage, including the cardiovascular system. While cardiomyopathy was the focus since the 1960s, the impact on the vasculature was comparatively neglected for about 40 years, when clinical studies correlating iron overload, oxidative stress, endothelial dysfunction, arterial stiffness and atherosclerosis reinforced an "iron hypothesis". Due to controversial results from some epidemiological studies investigating atherosclerotic events and iron levels, well-controlled trials and animal studies provided essential data about the influence of iron, per se, on the vasculature. As a result, the pathophysiology of vascular dysfunction in iron overload have been revisited. This review summarizes the knowledge obtained from epidemiological studies, animal models and "in vitro" cellular systems in recent decades, highlighting a more harmful than innocent role of iron excess for the vascular homeostasis, which supports our proposal to hereafter denominate "iron overload vasculopathy". Additionally, evidence-based potential therapeutic targets are pointed out to be tested in pre-clinical research that may be useful in cardiovascular protection for patients with iron overload syndromes.

Methamphetamine enhances caveolar transport of therapeutic agents across the rodent blood-brain barrier.

The blood-brain barrier (BBB) restricts clinically relevant accumulation of many therapeutics in the CNS. Low-dose methamphetamine (METH) induces fluid-phase transcytosis across BBB endothelial cells in vitro and could be used to enhance CNS drug delivery. Here, we show that low-dose METH induces significant BBB leakage in rodents ex vivo and in vivo. Notably, METH leaves tight junctions intact and induces transient leakage via caveolar transport, which is suppressed at 4°C and in caveolin-1 (CAV1) knockout mice. METH enhances brain penetration of both small therapeutic molecules, such as doxorubicin (DOX), and large proteins. Lastly, METH improves the therapeutic efficacy of DOX in a mouse model of glioblastoma, as measured by a 25% increase in median survival time and a significant reduction in satellite lesions. Collectively, our data indicate that caveolar transport at the adult BBB is agonist inducible and that METH can enhance drug delivery to the CNS.

Are there opportunities for women as head coaches in Brazil's national teams? The case of handball

Abstract Aim: This study aims to analyze the perceptions of women who hold leadership positions in sports on female participation as the head coach of the Brazilian women's handball national team. Method: We offer a qualitative case study. The collected data was through in-depth elite interviews. The interviewees' responses were analyzed and interpreted using the construction of categories. Results: The finds show perceptions of the categorization process. Three main categories emerged: 1) Prejudice. The interviewees affirm that the prejudice within the sport has been decreasing over the years. But it remains latent and continues to make difficult the continuity and rise of women in sports. 2) Professional and personal life. The interviewees affirm that Brazil is still a macho country, and even at a lower level, prejudice still exists in the universe of sports. The sport is known as a territory where men produce and demonstrate their masculinity; this favors the perception that coaches are usually men, having specific questions about the women's competence in that position, and that only men would be able to run teams. 3) Competence. The conciliation between family and professional life is a delicate situation, promotes conflicts, and does not favor the rise of women in positions of command. Nevertheless, the difficulty of reconciling personal and professional life, especially in high-performance sports, is necessary to leave home for extended periods for training or competition. Conclusion: The prejudice still is present despite its reduction over the years. The men domain the sports career, and for women, it is necessary to face the glass ceiling and prove their capacity constantly. Women's access to head coach teams, such as the Brazilian adult women's handball national team, is still a significant challenge.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Low-Cost Beamforming Concept for the Control of Radiation Patterns of Antenna Arrays Installed onto UAVs.

This paper presents a low-cost architecture that allows for beamforming with antenna arrays installed onto unmanned aerial vehicles (UAVs). Beam switching is proposed to improve the antenna gain towards the ground station with two three-element arrays installed below the wings of the UAV. The electromagnetic modeling of the complete structure (UAV and integrated antennas) was performed with commercial electromagnetic simulator Ansys HFSS. The radiation patterns were synthesized with particle swarm optimization (PSO). By employing lumped surface-mount device (SMD) components and switches, the design of the feeder to deliver proper excitation coefficients to the antennas is presented, and its performance was assessed by simulations. The proposed approach is demonstrated to be very effective with low-cost production.

Moderate-intensity aerobic training reduces cardiac damage attributable to experimental iron overload in rats.

NEW FINDINGS: What is the central question of this study? The current literature indicates that oxidative stress plays a major role in iron overload. Although exercise is a well-established approach to treat/prevent cardiovascular diseases, its effects on iron overload are not known. What is the main finding and its importance? Moderate-intensity aerobic training had benefits in a rodent model of iron-overload cardiomyopathy by improving the antioxidant capacity of the heart. After further confirmation by translational and clinical studies, we should consider using this non-pharmacological, highly accessible and easily executable adjuvant approach allied to other therapies to improve the quality of life of iron-overloaded patients. ABSTRACT: Iron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron-overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate-intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100 mg/kg, 5 days/week for 4 weeks); thereafter, the rats were kept sedentary or exercised (60 min/day, progressive aerobic training, 60-70% of maximal speed, 5 days/week on a treadmill) for 8 weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen type I and lipid peroxidation (TBARS), and release of creatine phosphokinase-MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase. In conclusion, moderate-intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non-pharmacological adjuvant therapy for iron-overload cardiomyopathy.

Novel MYT1 variants expose the complexity of oculo-auriculo-vertebral spectrum genetic mechanisms.

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by anomalies mainly involving the structures derived from the first and second pharyngeal arches. The spectrum presents with heterogeneous clinical features and complex etiology with genetic factors not yet completely understood. To date, MYT1 is the most important gene unambiguously associated with the spectrum and with functional data confirmation. In this work, we aimed to identify new single nucleotide variants (SNVs) affecting MYT1 in a cohort of 73 Brazilian patients diagnosed with OAVS. In addition, we investigated copy number variations (CNVs) encompassing this gene or its cis-regulatory elements and compared the frequency of these events in patients versus a cohort of 455 Brazilian control individuals. A new SNV, predicted as likely deleterious, was identified in five unrelated patients with OAVS. All five patients presented hearing impairment and orbital asymmetry suggesting an association with the variant. CNVs near MYT1, located in its neighboring topologically associating domain (TAD), were found to be enriched in patients when compared to controls, indicating a possible involvement of this region with OAVS pathogenicity. Our findings highlight the genetic complexity of the spectrum that seems to involve more than one variant type and inheritance patterns.