Sentimentos da mulher frente a gestação de alto risco / Sentimientos de la mujer frente al embarazo de alto riesgo / Women's feelings facing High-Risk pregnancy

Resumo Introdução: A gestação configura-se como um acontecimento único e memorável para a vida de uma mulher. A gravidez de alto risco é uma experiência estressante em razão dos riscos a que estão submetidos a mãe e o bebê e devido às mudanças que afetam negativamente o seu equilíbrio emocional. Objetivo: Identificar os sentimentos vivenciados pela gestante frente à gravidez de alto risco. Método: Descritivo e exploratório com abordagem qualitativa, com amostra por conveniência composta por mulheres com gestação de alto risco, selecionadas de acordo com a disponibilidade do serviço de internamento, até a saturação das entrevistas. A coleta dos dados foi realizada em um período de dois meses através de entrevistas guiadas por um roteiro. Os dados foram analisados por meio da técnica de análise de conteúdo segundo Minayo. Resultados: Fizeram parte 37 mulheres. Os resultados foram oeganizados nas categorias: Como se deu o diagnóstico de alto risco; Sentimentos ao descobrir que a gestação é/era de risco; Sentimentos em relação ao apoio familiar acerca da gestação de alto risco. Os sentimentos relatados pelas gestantes e puérperas que conviveram com a gravidez de alto risco, deixam evidentes os impactos que este evento traz não somente na saúde física sobretudo para a emocional, deixando as gestantes fragilizadas. Conclusão: Assim, o estudo nos permitiu perceber que os sentimentos vivenciados nesse processo podem interfir na vida dessas mulheres, e de forma negativa. Mas, que apesar dessa situação, estas expressam sentimentos ambíguos, pois mesmo com o risco gestacional, muitas mostram-se felizes pela dádiva de ser mãe.

Resumen Introducción: El embarazo se considera un evento único y memorable en la vida de una mujer. El embarazo de alto riesgo es una experiencia estresante debido a los riesgos a los que están expuestas tanto la madre como su bebé y a los cambios que afectan negativamente su equilibrio emocional. Objetivo: Identificar los sentimientos experimentados por las mujeres embarazadas frente a un embarazo de alto riesgo. Metodología: Descriptivo y exploratorio con enfoque cualitativo, con una muestra a conveniencia compuesta por mujeres con embarazos de alto riesgo, seleccionadas según la disponibilidad del servicio de hospitalización, hasta la saturación de las entrevistas. La recopilación de datos se llevó a cabo durante un período de dos meses a través de entrevistas guiadas. Los datos fueron analizados utilizando la técnica de análisis de contenido según Minayo. Resultados: Participaron 37 mujeres y los resultados se organizaron en las siguientes categorías: cómo se realizó el diagnóstico de alto riesgo; sentimientos al descubrir que el embarazo era de riesgo; sentimientos con respecto al apoyo familiar en relación con el embarazo de alto riesgo. Los sentimientos relatados por las mujeres embarazadas y posparto que vivieron un embarazo de alto riesgo evidencian los impactos que tiene este evento no solo en la salud física sino, especialmente, en el bienestar emocional, pues deja a las mujeres embarazadas en un estado de vulnerabilidad. Conclusión: El estudio nos permitió darnos cuenta de que los sentimientos experimentados en este proceso pueden interferir en la vida de estas mujeres de manera negativa. Sin embargo, a pesar de esta situación, muchas de ellas expresan sentimientos ambiguos, porque, incluso con el riesgo gestacional, están agradecidas por el regalo de la maternidad.

Abstract Introduction: Pregnancy is considered a unique and memorable event in a woman's life. High-risk pregnancy is a stressful experience due to the risks to which the mother and the baby are exposed, and due to the changes that negatively affect their emotional balance. Objective: To identify the feelings experienced by pregnant women facing high-risk pregnancy. Method: Descriptive and exploratory, employing a qualitative approach, the study featured a convenience sample of women with high-risk pregnancies, selected based on inpatient service availability, until interview saturation was achieved. Data collection was conducted over a two-month period through scripted interviews. Data analysis was performed utilizing Minayo's content analysis technique. Results: Thirty-seven women participated in the study. The results were categorized as follows: How the high-risk diagnosis was determined; Feelings upon discovering the pregnancy was high-risk; Feelings regarding family support regarding the high-risk pregnancy. The feelings reported by pregnant and postpartum women who experienced high-risk pregnancies clearly reveal the impacts this event has, not only on physical health, but especially on emotional well-being, leaving the pregnant women in a vulnerable state. Conclusion: The study allowed us to realize that the feelings experienced in this process can negatively interfere in the lives of these women. However, despite this situation, many of them express mixed feelings, because even with the gestational risk, they are grateful for the gift of motherhood.

Psychometric Properties of the Healthy Lifestyle Behaviors Scale in Portuguese Pregnant Women.

BACKGROUND: Pregnancy provides a privileged and opportune moment to implement interventions promoting healthy lifestyle behaviors and significantly improving perinatal outcomes. The Healthy Lifestyle Behaviors Scale (HLBES) can be used to assess health promoting behaviors, such as diet, physical activity, and mental health. PURPOSE: This study aimed to examine the psychometric properties of the HLBES in Portuguese pregnant women. METHODS: A methodological study was conducted on a convenience sample of 192 pregnant women receiving prenatal care. After cross-cultural adaptation, an exploratory factor analysis and internal consistency assessment were carried out to evaluate the psychometric properties of the scale. Data collected included the Healthy Lifestyle Beliefs Scale to assess the HLBES' criterion validity. RESULTS: Exploratory factor analysis with Varimax rotation yielded 2 subscales that explained 45.23% of the total variance. The scale revealed an overall internal consistency of 0.78 and a good criterion validity with the Healthy Lifestyle Beliefs Scale (r = 0.65, P < .01). CONCLUSION: Our results suggest that the HLBES is an instrument for reporting healthy lifestyle behaviors in Portuguese pregnant women; however, further studies are recommended. This scale can be used to not only describe healthy lifestyle behaviors in pregnant women but also to determine the effects of health promoting interventions.

Knowledge and perceived confidence of Brazilian psychiatrists about eating disorders´ diagnosis and treatment recommendations.

OBJECTIVE: To investigate Brazilian psychiatrists ́ knowledge and perceived confidence, both in diagnosis and in evidence-based treatments for eating disorders (ED). METHODS: In this cross-sectional study, 259 psychiatrists filled out an online form including: sociodemographic data, questions about ED diagnosis and management based on standard guidelines. Descriptive statistics described sample characteristics and levels of ED knowledge and perceived confidence. RESULTS: Sample was composed mainly by women (65,64%), with mean age of 42.86, from the Southeast of Brazil (56,37%), working predominantly in private practice (59,85%), with less than ten years of experience in Psychiatry (51,74%). We found that 33.21% of participants correctly chose diagnostic criteria for anorexia nervosa (AN); 29.73% for bulimia nervosa (BN), and 38.22% for binge eating disorder (BED). Correct answers for therapeutic options were similar in BN and BED (20.8%), being considerably lower for AN (2.7%). Additionally, reported ED training were: 15.1% during medical school; 59.8% during medical residency/postgraduate studies; 58.7% as complementary training. Only 8.89% felt satisfied with their ED training; 50.97% felt confident diagnosing ED and 37.07% in managing ED patients. CONCLUSION: These results demonstrated an important gap in ED knowledge of Brazilian psychiatrists, and its consequences on their confidence and competence in managing ED patients.

Combination of Tele-Cardiology Tools for Cardiovascular Risk Stratification in Primary Care: Data from the PROVAR+ Study. / Combinação de Ferramentas de Telecardiologia para Estratificação de Risco Cardiovascular na Atenção Primária: Dados do Estudo PROVAR.

BACKGROUND: Tele-cardiology tools are valuable strategies to improve risk stratification. OBJECTIVE: We aimed to evaluate the accuracy of tele-electrocardiography (ECG) to predict abnormalities in screening echocardiography (echo) in primary care (PC). METHODS: In 17 months, 6 health providers at 16 PC units were trained on simplified handheld echo protocols. Tele-ECGs were recorded for final diagnosis by a cardiologist. Consented patients with major ECG abnormalities by the Minnesota code, and a 1:5 sample of normal individuals underwent clinical questionnaire and screening echo interpreted remotely. Major heart disease was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion, or wall-motion abnormalities. Association between major ECG and echo abnormalities was assessed by logistic regression as follows: 1) unadjusted model; 2) model 1 adjusted for age/sex; 3) model 2 plus risk factors (hypertension/diabetes); 4) model 3 plus history of cardiovascular disease (Chagas/rheumatic heart disease/ischemic heart disease/stroke/heart failure). P-values < 0.05 were considered significant. RESULTS: A total 1,411 patients underwent echo; 1,149 (81%) had major ECG abnormalities. Median age was 67 (IQR 60 to 74) years, and 51.4% were male. Major ECG abnormalities were associated with a 2.4-fold chance of major heart disease on echo in bivariate analysis (OR = 2.42 [95% CI 1.76 to 3.39]), and remained significant after adjustments in models (p < 0.001) 2 (OR = 2.57 [95% CI 1.84 to 3.65]), model 3 (OR = 2.52 [95% CI 1.80 to3.58]), and model 4 (OR = 2.23 [95%CI 1.59 to 3.19]). Age, male sex, heart failure, and ischemic heart disease were also independent predictors of major heart disease on echo. CONCLUSIONS: Tele-ECG abnormalities increased the likelihood of major heart disease on screening echo, even after adjustments for demographic and clinical variables.

FUNDAMENTO: As ferramentas de telecardiologia são estratégias valiosas para melhorar a estratificação de risco. OBJETIVO: Objetivamos avaliar a acurácia da tele-eletrocardiografia (ECG) para predizer anormalidades no ecocardiograma de rastreamento na atenção primária. MÉTODOS: Em 17 meses, 6 profissionais de saúde em 16 unidades de atenção primária foram treinados em protocolos simplificados de ecocardiografia portátil. Tele-ECGs foram registrados para diagnóstico final por um cardiologista. Pacientes consentidos com anormalidades maiores no ECG pelo código de Minnesota e uma amostra 1:5 de indivíduos normais foram submetidos a um questionário clínico e ecocardiograma de rastreamento interpretado remotamente. A doença cardíaca grave foi definida como doença valvular moderada/grave, disfunção/hipertrofia ventricular, derrame pericárdico ou anormalidade da motilidade. A associação entre alterações maiores do ECG e anormalidades ecocardiográficas foi avaliada por regressão logística da seguinte forma: 1) modelo não ajustado; 2) modelo 1 ajustado por idade/sexo; 3) modelo 2 mais fatores de risco (hipertensão/diabetes); 4) modelo 3 mais história de doença cardiovascular (Chagas/cardiopatia reumática/cardiopatia isquêmica/AVC/insuficiência cardíaca). Foram considerados significativos valores de p < 0,05. RESULTADOS: No total, 1.411 pacientes realizaram ecocardiograma, sendo 1.149 (81%) com anormalidades maiores no ECG. A idade mediana foi de 67 anos (intervalo interquartil de 60 a 74) e 51,4% eram do sexo masculino. As anormalidades maiores no ECG se associaram a uma chance 2,4 vezes maior de doença cardíaca grave no ecocardiograma de rastreamento na análise bivariada (OR = 2,42 [IC 95% 1,76 a 3,39]) e permaneceram significativas (p < 0,001) após ajustes no modelo 2 (OR = 2,57 [IC 95% 1,84 a 3,65]), modelo 3 (OR = 2,52 [IC 95% 1,80 a 3,58]) e modelo 4 (OR = 2,23 [IC 95% 1,59 a 3,19]). Idade, sexo masculino, insuficiência cardíaca e doença cardíaca isquêmica também foram preditores independentes de doença cardíaca grave no ecocardiograma. CONCLUSÕES: As anormalidades do tele-ECG aumentaram a probabilidade de doença cardíaca grave no ecocardiograma de rastreamento, mesmo após ajustes para variáveis demográficas e clínicas.

Agreement between Handheld and Standard Echocardiography for Diagnosis of Latent Rheumatic Heart Disease in Brazilian Schoolchildren from High-Prevalence Settings (Agreement between Screening and Standard Echo for RHD).

Introduction: Handheld echocardiography (echo) is the tool of choice for rheumatic heart disease (RHD) screening. We aimed to assess the agreement between screening and standard echo for latent RHD diagnosis in schoolchildren from an endemic setting. Methods: Over 14 months, 3 nonphysicians used handheld machines and the 2012 WHF Criteria to determine RHD prevalence in consented schoolchildren from Brazilian low-income public schools. Studies were interpreted by telemedicine by 3 experts (Brazil, US). RHD-positive children (borderline/definite) and those with congenital heart disease (CHD) were referred for standard echo, acquired and interpreted by a cardiologist. Agreement between screening and standard echo, by WHF subgroups, was assessed. Results: 1390 students were screened in 6 schools, with 110 (7.9%, 95% CI 6.5-9.5) being screen positive (14 ± 2 years, 72% women). Among 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline, and 1 to normal. Among 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) reclassified as definite RHD, and 2 had mild CHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criterion was B (isolated mitral regurgitation, 64%), followed by A (2 mitral valve morphological features, 31%). In 1 patient with definite RHD reclassified to normal, the WHF criterion was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3-4.2). Conclusions: Although practical, RHD screening with handheld devices tends to overestimate prevalence.

Sox21b underlies the rapid diversification of a novel male genital structure between Drosophila species.

The emergence and diversification of morphological novelties is a major feature of animal evolution.1,2,3,4,5,6,7,8,9 However, relatively little is known about the genetic basis of the evolution of novel structures and the mechanisms underlying their diversification. The epandrial posterior lobes of male genitalia are a novelty of particular Drosophila species.10,11,12,13 The lobes grasp the female ovipositor and insert between her abdominal tergites and, therefore, are important for copulation and species recognition.10,11,12,14,15,16,17 The posterior lobes likely evolved from co-option of a Hox-regulated gene network from the posterior spiracles10 and have since diversified in morphology in the D. simulans clade, in particular, over the last 240,000 years, driven by sexual selection.18,19,20,21 The genetic basis of this diversification is polygenic but, to the best of our knowledge, none of the causative genes have been identified.22,23,24,25,26,27,28,29,30 Identifying the genes underlying the diversification of these secondary sexual structures is essential to understanding the evolutionary impact on copulation and species recognition. Here, we show that Sox21b negatively regulates posterior lobe size. This is consistent with expanded Sox21b expression in D. mauritiana, which develops smaller posterior lobes than D. simulans. We tested this by generating reciprocal hemizygotes and confirmed that changes in Sox21b underlie posterior lobe evolution between these species. Furthermore, we found that posterior lobe size differences caused by the species-specific allele of Sox21b significantly affect copulation duration. Taken together, our study reveals the genetic basis for the sexual-selection-driven diversification of a novel morphological structure and its functional impact on copulatory behavior.

Spin-1/2 Ising ladder with randomly coupled rung interaction and transverse magnetic field.

The quantum spin-1/2 Ising ladder with homogeneous side rail interaction and disordered rung interaction in the presence of a random site transverse magnetic field has been studied using the method of recurrence relations in the high-temperature limit. The first six recurrants have been exactly calculated, and a linear extrapolation process has been used to obtain a total of 100 recurrants. This extrapolation allows us to extend the analysis to longer times. Both the rung coupling and the transverse field obey a bimodal distribution. The time autocorrelation functions of the z-component dynamic spin variable have been obtained. We have considered several cases of rung and transverse field distributions, as well as several values of the Hamiltonian parameters. The results show that the disorder present in the rung interaction and external transverse field affects the behavior of the temporal autocorrelation and the spectral functions in all studied cases. In addition, the interesting case where the rung interactions and the transverse magnetic field are correlated has also been studied. In general, transition in the dynamics of the system from individual to collective mode was observed depending on the dominant kind of interaction in the sites, that is, whether most of the sites were subject to a strong external field or strong interchain local interactions.

Assessment of Suitability for Percutaneous Mitral Commissurotomy: A Contemporary Review of Key Anatomical Criteria and Predictive Models.

The immediate result of percutaneous balloon mitral commissurotomy (PMC) is largely determined by the anatomy of the mitral valve complex. Several scores and models have been developed to assess anatomical suitability for PMC. Although none has an optimal predictive power, these models look at the valvular apparatus from different perspectives bearing the potential for a complementary role.

Correlation of blood-based immune molecules with cardiac gene expression profiles reveals insights into Chagas cardiomyopathy pathogenesis.

Introduction: Understanding compartmentalized immune responses in target organs is crucial for elucidating the pathogenesis of various diseases. However, obtaining samples from affected vital organs often poses safety challenges. In this study, we aimed to investigate potential correlations between the levels of disease-associated immune molecules in the bloodstream with their gene expression profiles in the hearts of patients suffering from Chagas Cardiomyopathy (CCC). This debilitating and often fatal condition is caused by infection with the protozoan Trypanosoma cruzi. Methods: Blood samples were analyzed using the Bio-Plex platform. Gene Expression Omnibus (GEO) database was used to determine gene expression profile in heart tissue from CCC and non-Chagas controls (CTRL). Results: Elevated levels of inflammatory cytokines were detected in the plasma of CCC patients, and these levels correlated with clinical indicators of deteriorating cardiac function. Notably, 75% of the soluble factors assessed in the plasma exhibited a consistent relationship with their gene expression levels in the cardiac tissue of CCC patients. Analysis of interactions and signaling pathways related to these molecules revealed an overrepresentation of inflammatory pathways in both blood and heart compartments. Moreover, we identified that differentially expressed genes in CCC cardiac tissue were primarily associated with T-cell signaling pathways and correlated with the presence of CD8+ T cells in the myocardium. Discussion: Our findings establish a strong correlation between relevant immune molecules and their signaling pathways in both the blood and heart tissue in CCC. This validates the use of blood as a non-invasive medium for understanding immunopathology and identifying markers for cardiac dysfunction in Chagas disease.

Development of Healthy Snacks Incorporating Meal from Tenebrio molitor and Alphitobius diaperinus Using 3D Printing Technology.

This study analyzes the nutritional properties of edible insects, specifically Tenebrio molitor and Alphitobius diaperinus, and explores the potential of 3D printing technology to introduce a nutritious and tasty alternative to essential nutrients for Western consumers. An original formulation for the printing of snacks with microalgae was adapted to incorporate edible insects. Concentrations of 10% of edible insects, both isolated and mixed, were incorporated into the developed ink-doughs. Stress and frequency sweeps were performed on the doughs to understand the rheology and the impact on the internal structure to better adapt these materials to the 3D printing process. The nutritional profile of the developed snacks was assessed, revealing a significant amount of protein, enough to claim the snacks as a "source of protein", as well as an increased mineral profile, when compared to the control snack. The antioxidant profile and total phenolic content were equally assessed. Finally, a sensory analysis test was performed, comparing the control snack to three other samples containing 10% T. molitor, 10% A. diaperinus and 5% + 5% of T. molitor and A. diaperinus, respectively, resulting in a preference for the A. diaperinus and for the combination of the two insects. Considered as a "novel food", foods incorporating edible insects represent, in fact, the reintroduction of foods used in the West before the Middle Ages, when the Judeo-Christian tradition began to consider insects as not kosher. Educating consumers about the transition to novel foods can be helped by 3D printing food, as an innovative process that can be used to design creative rich animal protein snacks that make final products more appealing and acceptable to consumers.

Deployment of Point-of-Care Echocardiography to Improve Cardiac Diagnostic Access Among American Indians.

BACKGROUND: American Indians face significant barriers to diagnosis and management of cardiovascular disease. We sought to develop a real-world implementation model for improving access to echocardiography within the Indian Health Service, the American Indian Structural Heart Disease Partnership. METHODS AND RESULTS: The American Indian Structural Heart Disease Partnership was implemented and evaluated via a 4-step process of characterizing the system where it would be instituted, building point-of-care echocardiography capacity, deploying active case finding for structural heart disease, and evaluating the approach from the perspective of the clinician and patient. Data were collected and analyzed using a parallel convergent mixed methods approach. Twelve health care providers successfully completed training in point-of-care echocardiography. While there was perceived usefulness of echocardiography, providers found it difficult to integrate screening point-of-care echocardiography into their workday given competing demands. By the end of 12 months, 6 providers continued to actively utilize point-of-care echocardiography. Patients who participated in the study felt it was an acceptable and effective approach. They also identified access to transportation as a notable challenge to accessing echocardiograms. Over the 12-month period, a total of 639 patients were screened, of which 36 (5.6%) had a new clinically significant abnormal finding. CONCLUSIONS: The American Indian Structural Heart Disease Partnership model exhibited several promising strategies to improve access to screening echocardiography for American Indian populations. However, competing priorities for Indian Health Service providers' time limited the amount of integration of screening echocardiography into outpatient practice. Future endeavors should explore community-based solutions to develop a more sustainable model with greater impact on case detection, disease management, and improved outcomes.

Altered expression of Sialyl Lewis X in experimental models of Parkinson's disease.

The mechanisms underlying neurodegeneration in Parkinson's disease (PD) are still not fully understood. Glycosylation is an important post-translational modification that affects protein function, cell-cell contacts and inflammation and can be modified in pathologic conditions. Although the involvement of aberrant glycosylation has been proposed for PD, the knowledge of the diversity of glycans and their role in PD is still minimal. Sialyl Lewis X (sLeX) is a sialylated and fucosylated tetrasaccharide with essential roles in cell-to-cell recognition processes. Pathological conditions and pro-inflammatory mediators can up-regulate sLeX expression on cell surfaces, which has important consequences in intracellular signalling and immune function. Here, we investigated the expression of this glycan using in vivo and in vitro models of PD. We show the activation of deleterious glycation-related pathways in mouse striatum upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin-based model of PD. Importantly, our results show that MPTP triggers the presentation of more proteins decorated with sLeX in mouse cortex and striatum in a time-dependent manner, as well as increased mRNA expression of its rate-limiting enzyme fucosyltransferase 7. sLeX is expressed in neurons, including dopaminergic neurons, and microglia. Although the underlying mechanism that drives increased sLeX epitopes, the nature of the protein scaffolds and their functional importance in PD remain unknown, our data suggest for the first time that sLeX in the brain may have a role in neuronal signalling and immunomodulation in pathological conditions. KEY MESSAGES: MPTP triggers the presentation of proteins decorated with sLeX in mouse brain. MPTP triggers the expression of sLeX rate-limiting enzyme FUT 7 in striatum. sLeX is expressed in neurons, including dopaminergic neurons, and microglia. sLeX in the brain may have a role in neuronal signalling and immunomodulation.

Epigenetic Mechanisms Histone Deacetylase-Dependent Regulate the Glioblastoma Angiogenic Matrisome and Disrupt Endothelial Cell Behavior In Vitro.

Glioblastoma (GBM) is the most aggressive brain tumor and different efforts have been employed in the search for new drugs and therapeutic protocols for GBM. Epitranscriptomics has shed light on new druggable Epigenetic therapies specifically designed to modulate GBM biology and behavior such as Histone Deacetylase inhibitors (iHDAC). Although the effects of iHDAC on GBM have been largely explored, there is a lack of information on the underlaying mechanisms HDAC-dependent that modulate the repertoire of GBM secreted molecules focusing on the set of Extracellular Matrix (ECM) associated proteins, the Matrisome, that may impact the surrounding tumor microenvironment. To acquire a better comprehension of the impacts of HDAC activity on the GBM Matrisome, we studied the alterations on the Matrisome-associated ECM regulators, Core Matrisome ECM glycoproteins, ECM-affiliated proteins and Proteoglycans upon HDAC inhibition in vitro as well as their relationship with glioma pathophysiological/clinical features and angiogenesis. For this, U87MG GBM cells were treated for with iHDAC or vehicle (control) and the whole secretome was processed by Mass Spectrometry NANOLC-MS/MS. In silico analyses revealed that proteins associated to the Angiogenic Matrisome (AngioMatrix), including Decorin, ADAM10, ADAM12 and ADAM15 were differentially regulated in iHDAC versus control secretome. Interestingly, genes coding for the Matrisome proteins differentially regulated were found mutated in patients and were correlated to glioma pathophysiological/clinical features. In vitro functional assays, using HBMEC endothelial cells exposed to the secretome of control or iHDAC treated GBM cells, coupled to 2D and 3D GBM cell culture system, showed impaired migratory capacity of endothelial cells and disrupted tubulogenesis in a Fibronectin and VEGF independent fashion. Collectively, our study provides understanding of epigenetic mechanisms HDAC-dependent to key Matrisomal proteins that may contribute to identify new druggable Epigenetic therapies or gliomagenesis biomarkers with relevant implications to improve therapeutic protocols for this malignancy.

Exploring the Chagas disease-Stroke 'Connection': Findings from a Large Multicenter Study.

INTRODUCTION: Strokes are traditionally attributed to risk factors like aging, hypertension, diabetes, and atherosclerosis. Chagas disease has emerged as an important risk factor for stroke in Latin American. Our study aims at describing the largest cohort of patients with Chagas disease and ischemic stroke and determining variables associated with stroke recurrence and cardioembolic cause. METHODS: This study is the result of a national multicenter cohort study conducted in Brazil. The study spanned from January 2009 to December 2016 and involved a comprehensive retrospective analysis of medical records of patients with both Chagas disease and stroke. This cohort comprised 499 individuals from diverse Brazilian regions, focusing on vascular risk factors and the epidemiological variables associated with Chagas disease and stroke. RESULTS: Our findings underscore the significant prevalence of traditional vascular risk factors among Chagas disease patients who had stroke. 81% of patients had hypertension, 56% dyslipidemia and 25% diabetes. We observed a 29.7% recurrence rate, especially within the cardioembolic subgroup. 56% of the patients had embolic stroke of undetermined source (ESUS). Specific EKG abnormalities were associated with an increased risk of cardioembolic etiology (with three altered results increasing 81fold the chance of the stroke being of cardioembolic nature). Age emerged as a protective factor (OR:0.98, CI 0.970 - 0.997) against cardioembolic etiology. Anticoagulation therapy was associated with reduced risk (OR:0.221 |CI 0.104 - 0.472), highlighting the importance of accurate etiological classification. Conversely, female gender(OR:1.83 CI 1.039 - 3.249) emerged as a significant risk factor for stroke recurrence. CONCLUSION: This study significantly advances our epidemiological understanding of the intersection between Chagas disease and stroke. It emphasizes the critical need for extensive epidemiological investigations, a deeper comprehension of stroke recurrence determinants, and accurate etiological classification to reduce the ESUS population. Our findings have substantial clinical implications, suggesting the need of control of vascular risk factors and comorbidities and hold promise for improving patient care and reducing the burden of Chagas disease and stroke worldwide.

Gastrointestinal Manifestations of Chagas Disease: A Systematic Review with Meta-Analysis.

The aims of this study were to estimate the prevalence of gastrointestinal manifestations among individuals with positive serology for Chagas disease (ChD) and to describe the clinical gastrointestinal manifestations of the disease. A systematic review with meta-analysis was conducted based on the criteria and recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Scopus, Virtual Health Library, Web of Science, and Embase databases were used to search for evidence. Two reviewers independently selected eligible articles and extracted data. RStudio® software was used for the meta-analysis. For subgroup analysis, the studies were divided according to the origin of the individuals included: 1) individuals from health units were included in the health care service prevalence analysis, and 2) individuals from the general population were included in the population prevalence analysis. A total of 2,570 articles were identified, but after removal of duplicates and application of inclusion criteria, 24 articles were included and 21 were part of the meta-analysis. Most of the studies were conducted in Brazil. Radiological diagnosis was the most frequent method used to identify the gastrointestinal clinical form. The combined effect of meta-analysis studies showed a prevalence of gastrointestinal manifestations in individuals with ChD of 12% (95% CI, 8.0-17.0%). In subgroup analysis, the prevalence for studies involving health care services was 16% (95% CI, 11.0-23.0%), while the prevalence for population-based studies was 9% (95% CI, 5.0-15.0%). Megaesophagus and megacolon were the main forms of ChD presentation in the gastrointestinal form. The prevalence of gastrointestinal manifestations of ChD was 12%. Knowing the prevalence of ChD in its gastrointestinal form is an important step in planning health actions for these patients.

NPC1-like phenotype, with intracellular cholesterol accumulation and altered mTORC1 signaling in models of Parkinson's disease.

Disruption of brain cholesterol homeostasis has been implicated in neurodegeneration. Nevertheless, the role of cholesterol in Parkinson's Disease (PD) remains unclear. We have used N2a mouse neuroblastoma cells and primary cultures of mouse neurons and 1-methyl-4-phenylpyridinium (MPP+), a known mitochondrial complex I inhibitor and the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), known to trigger a cascade of events associated with PD neuropathological features. Simultaneously, we utilized other mitochondrial toxins, including antimycin A, oligomycin, and carbonyl cyanide chlorophenylhydrazone. MPP+ treatment resulted in elevated levels of total cholesterol and in a Niemann Pick type C1 (NPC1)-like phenotype characterized by accumulation of cholesterol in lysosomes. Interestingly, NPC1 mRNA levels were specifically reduced by MPP+. The decrease in NPC1 levels was also seen in midbrain and striatum from MPTP-treated mice and in primary cultures of neurons treated with MPP+. Together with the MPP+-dependent increase in intracellular cholesterol levels in N2a cells, we observed an increase in 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and a concomitant increase in the phosphorylated levels of mammalian target of rapamycin (mTOR). NPC1 knockout delayed cell death induced by acute mitochondrial damage, suggesting that transient cholesterol accumulation in lysosomes could be a protective mechanism against MPTP/MPP+ insult. Interestingly, we observed a negative correlation between NPC1 protein levels and disease stage, in human PD brain samples. In summary, MPP+ decreases NPC1 levels, elevates lysosomal cholesterol accumulation and alters mTOR signaling, adding to the existing notion that PD may rise from alterations in mitochondrial-lysosomal communication.

Pattern of maximum voluntary contraction in patients with temporomandibular disorder before and after speech therapy with and without use of elastic bandages / Padrão de contração voluntária máxima em pacientes com disfunção temporomandibular antes e após terapia fonoaudiológica com e sem uso de bandagem elástica

ABSTRACT Purpose: to verify if there is an electromyographic difference during maximal (maximum) voluntary contraction of the masseter and temporalis muscles in patients with temporomandibular disorders, before and after speech therapy intervention with and without the use of therapeutic elastic bandages. Methods: an analysis of secondary data from a clinical intervention study, carried out with 17 adult volunteers, diagnosed with temporomandibular muscle dysfunction with or without disc displacement with reduction. The Bandage Group received manual therapy associated with elastic bandages and the No Bandage Group received only manual therapy. Surface electromyography was performed to record the Maximum Voluntary Contraction before and after four weeks of speech therapy intervention. For exploratory analysis, the Mann Whitney and Wilcoxon paired tests were used, with P<0.05. Results: in the Bandage Group, there was a statistically significant decrease in electrical activity during Maximum Voluntary Contraction in the masseter and temporalis muscles on the left side at the post-therapeutic moment. Comparing the pre- and post-intervention between Bandage Group and No Bandage Group, a statistical difference was found in the electrical activity values of the Maximum Voluntary Contraction in the left temporal muscle. Conclusion: manual myofunctional speech therapy, associated or not with the use of therapeutic elastic bandages, impacts the muscle activity of the masseter and temporal muscles during Maximum Voluntary Contraction, whether the values demonstrate relaxation and/or equivalence of the electromyographic values of the masticatory muscles.

RESUMO Objetivo: verificar se há diferença eletromiográfica durante contração voluntária máxima dos músculos masseter e temporal de pacientes com disfunção temporomandibular, antes e após intervenção fonoaudiológica com e sem uso de bandagem elástica terapêutica. Métodos: foi realizada a análise de dados secundários de estudo do tipo intervenção clínica, com 17 voluntárias, adultas, com diagnóstico de disfunção temporomandibular muscular com ou sem deslocamento de disco com redução. O Grupo Bandagem recebeu terapia manual associada à bandagem elástica e o Grupo Sem Bandagem recebeu apenas terapia manual. Foi realizada eletromiografia de superfície para registro da contração voluntária máxima antes e após quatro semanas de intervenção fonoaudiológica. Para análise exploratória foram utilizados os testes: Mann Whitney e Wilcoxon Pareado, com p<0,05. Resultados: no Grupo Bandagem, houve diminuição estatisticamente significante da atividade elétrica durante a Contração Voluntária Máxima nos músculos masseter e temporal do lado esquerdo no momento pós-terapêutico. Na comparação do pré e pós-intervenção entre Grupo Bandagem e Grupo Sem Bandagem, constatou-se diferença estatística nos valores da atividade elétrica de Contração Voluntária Máxima no músculo temporal esquerdo. Conclusão: a terapia fonoaudiológica miofuncional manual, associada ou não ao uso da bandagem elástica terapêutica, impacta a atividade muscular dos músculos masseter e temporal durante a Contração Voluntária Máxima, sejam os valores demonstrando relaxamento e/ou equivalência dos valores eletromiográficos da musculatura mastigatória.

Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis.

BACKGROUND: Secondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. METHODS: We included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. RESULTS: 799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16-1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7-9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59-0.69)). CONCLUSIONS: The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.