Pharmacogenetics of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in cardiovascular diseases.

Cardiovascular diseases (CVDs) have a high mortality rate, and despite the several available therapeutic targets, non-response to antihypertensives remains a common problem. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are important classes of drugs recommended as first-line therapy for several CVDs. However, response to ACEIs and ARBs varies among treated patients. Pharmacogenomics assesses how an individual's genetic characteristics affect their likely response to drug therapy. Currently, numerous studies suggest that genetic polymorphisms may contribute to variability in drug response. Moreover, further studies evaluating gene-gene interactions within signaling pathways in response to antihypertensives might help to unravel potential genetic predictors for antihypertensive response. This review summarizes the pharmacogenetic data for ACEIs and ARBs in patients with CVD, and discusses the potential pharmacogenetics of these classes of antihypertensives in clinical practice. However, replication studies in different populations are needed. In addition, studies that evaluate gene-gene interactions that share signaling pathways in the response to antihypertensive drugs might facilitate the discovery of genetic predictors for antihypertensive response.

Fish Fillet Analogue Using Formulation Based on Mushroom (Pleurotus ostreatus) and Enzymatic Treatment: Texture, Sensory, Aromatic Profile and Physicochemical Characterization.

The growing demand for alternative sources of non-animal proteins has stimulated research in this area. Mushrooms show potential in the innovation of plant-based food products. In this study, the aim was to develop prototype fish fillets analogues from Pleurotus ostreatus mushrooms applying enzymatic treatment (ß-glucanase and transglutaminase-TG). A Plackett-Burman 20 experimental design was used to optimize forty variables. Oat flour (OF) exerted a positive effect on the hardness and gumminess texture parameters but a negative effect on cohesiveness and resilience. Soy protein isolate (SPI) exhibited a positive effect on elasticity, gumminess and chewiness, while acacia gum had a negative effect on elasticity, cohesiveness and resilience. After sensory analysis the assay with 1% cassava starch, 5% OF, 5% SPI, 0.1% transglutaminase (240 min/5 °C), 1% coconut oil, 1% soybean oil, 0.2% sodium tripolyphosphate, 0.6% ß-glucanase (80 °C/10 min) and without ß-glucanase inactivation was found to exhibit greater similarity to fish fillet. The classes hydrocarbons, alcohols and aldehydes are the predominant ones in aromatic profile analysis by chromatography and electronic nose. It is concluded that a mushroom-based analogue of fish fillet can be prepared using enzymatic treatment with TG.

Association of uric acid with length of stay and mortality in pediatric hospitalized population.

PURPOSE: Elevated uric acid (UA) levels have been associated with acute and chronic diseases, which could affect the prognosis of pediatric hospitalized patients. However, the association of UA levels with length of hospital stay (LOS) and mortality in hospitalized children and adolescents remains unknown. Therefore, the aim of this study was to evaluate the association of serum UA levels with in-hospital mortality and prolonged LOS in hospitalized children and adolescents. METHODS: A retrospective cohort study was conducted, involving 128 patients under 18 years of age, admitted to a tertiary-care hospital between January 2014 and December 2018. UA levels were assessed with an average of 3 days before the in-hospital outcome (discharge or death). Logistic regression was used to determine the association of UA with prolonged LOS (defined as over 30 days of hospitalization), while Cox regression multivariate analysis was employed to assess UA as a predictor of in-hospital mortality. RESULTS: UA levels showed an inverse association with prolonged LOS. Specifically, for every 1 mg/dL increase in UA level, the odds of experiencing prolonged LOS decreased by 31% (OR = 0.69; 95% CI: 0.50-0.95). Additionally, individuals with elevated UA levels had lower odds of prolonged LOS (OR = 0.23; 95% CI: 0.08-0.66). However, UA levels were not associated with in-hospital mortality (HR = 1.63; 95% CI: 0.94-2.82). CONCLUSION: Serum UA was inversely associated with LOS among children and adolescents, but no association was observed with in-hospital mortality.

Serologic profiling of D variants in donor routine: unveiling the impact on false-negative results and alloimmunization.

The high number of D variants can lead to the unnecessary use of Rh immune globulin, overuse of D- RBC units, and anti-D allommunization. D variant prevalence varies among ethnic groups, and knowledge of the main variants present in a specific population, their behavior in serologic tests, and their impact on clinical practice is crucial to define the best serologic tests for routine use. The present study aimed to explore the serologic profile of D variants and to determine which variants are most associated with false-negative D typing results and alloimmunization. Donor samples were selected in two study periods. During the first period, D typing was performed on a semi-automated instrument in microplates, and weak D tests were conducted in tube or gel tests. In the second period, D typing was carried out using an automated instrument with microplates, and weak D tests were performed in solid phase. Samples from patients typed as D+ with anti-D were also selected. All samples were characterized by molecular testing. A total of 37 RHD variants were identified. Discrepancies and atypical reactivity without anti-D formation were observed in 83.4 percent of the samples, discrepant D typing results between donations were seen in 12.3 percent, and D+ patients with anti-D comprised 4.3 percent. DAR1.2 was the most prevalent variant. Weak D type 38 was responsible for 75 percent of discrepant samples, followed by weak D type 11, predominantly detected by solid phase. Among the D variants related to alloimmunization, DIVa was the most prevalent, which was not recognized by serologic testing; the same was true for DIIIc. The results highlight the importance of selecting tests for donor screening capable of detecting weak D types 38 and 11, especially in populations where these variants are more prevalent. In pre-transfusion testing, it is crucial that D typing reagents demonstrate weak reactivity with DAR variants; having a serologic strategy to recognize DIVa and DIIIc is also valuable.

Characterization of flours from the aroeira leaf (Schinus terebinthifolius Raddi), obtained by different drying methods.

The present work aimed at the development and characterization of aroeira leaf flour (Schinus terebinthifolius Raddi), obtained by lyophilization and drying in an air circulation oven. The technological, physical, physico-chemical, morphological, functional, and microbiological aspects were analyzed. Physico-chemical analysis identified the following properties with values provided respectively for fresh leaves (FOin) and flours (FES and FLIO): low water activity (0.984, 0.370, 0.387 g/100 g), moisture (64.52, 5.37, 7.97 g /100 g), ash (2.69, 6.51, and 6.89 g/100 g), pH (0.89, 4.45, 4.48 g/100 g), lipids (0.84, 1.67, 5.23 g/100 g), protein (3.29, 8.23, 14.12 g/100 g), carbohydrates (17.02, 53.12, 33.02 g/100 g), ascorbic acid (19.70, 34.20, 36.90 mg/100 g). Sources of fiber from plant leaves and flours (11.64, 25.1, 32.89 g/100 g) showed increased levels of luminosity. For NMR, the presence of aliphatic and aromatic compounds with olefinic hydrogens and a derivative of gallic acid were detected. The most abundant minerals detected were potassium and calcium. Micrographs identified the presence of irregular, non-uniform, and sponge-like particles. The main sugars detected were: fructose, glucose, and maltose. Malic, succinic, citric, lactic, and formic acids were found. Fifteen phenolic compounds were identified in the samples, highlighting: kaempferol, catechin, and caffeic acid. The values ​​found for phenolics were (447, 716.66, 493.31 mg EAG/100 g), flavonoids (267.60, 267.60, 286.26 EC/100 g). Antioxidant activity was higher using the ABTS method rather than FRAP for analysis of FOin, FES, and FLIO. Since the flours of the aroeira leaf have an abundant matrix of nutrients with bioactive properties and antioxidant activity, they have a potential for technological and functional use when added to food.

Multi-omic QTL mapping in early developmental tissues reveals phenotypic and temporal complexity of regulatory variants underlying GWAS loci.

Most GWAS loci are presumed to affect gene regulation, however, only ∼43% colocalize with expression quantitative trait loci (eQTLs). To address this colocalization gap, we identify eQTLs, chromatin accessibility QTLs (caQTLs), and histone acetylation QTLs (haQTLs) using molecular samples from three early developmental (EDev) tissues. Through colocalization, we annotate 586 GWAS loci for 17 traits by QTL complexity, QTL phenotype, and QTL temporal specificity. We show that GWAS loci are highly enriched for colocalization with complex QTL modules that affect multiple elements (genes and/or peaks). We also demonstrate that caQTLs and haQTLs capture regulatory variations not associated with eQTLs and explain ∼49% of the functionally annotated GWAS loci. Additionally, we show that EDev-unique QTLs are strongly depleted for colocalizing with GWAS loci. By conducting one of the largest multi-omic QTL studies to date, we demonstrate that many GWAS loci exhibit phenotypic complexity and therefore, are missed by traditional eQTL analyses.

Single nucleotide polymorphism (SNP) rs4291 of the angiotensin-converting enzyme (ACE) gene is associated with the response to losartan treatment in hypertensive patients.

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.

Qualitative and quantitative changes in mitochondrial DNA associated with cervical cancer: A comprehensive review.

Cervical cancer is the fourth most commonly diagnosed cancer in women and is considered a preventable disease, as vaccination and screening programs effectively reduce its incidence and mortality rates. Disease physiopathology and malignant cell transformation is a complex process, but it is widely known that high-risk HPV (hrHPV) infection is a necessary risk factor for cancer development. Mitochondria, cell organelles with important bioenergetic and biosynthetic functions, are important for cell energy production, cell growth, and apoptosis. Mitochondrial DNA is a structure that is particularly susceptible to quantitative (mtDNA copy number variation) and qualitative (sequence variations) alterations that are associated with various types of cancer. Novel biomarkers with diagnostic and prognostic value in cervical cancer can be evaluated to provide higher specificity and complement hrHPV molecular testing, which is the most recommended method for primary screening. In accordance with this, this review aimed to assess mitochondrial alterations associated with cervical cancer in clinical cervicovaginal samples, in order to unravel their possible role as specific diagnostic and prognostic biomarkers for cervical malignancy, and also to guide the understanding of their involvement in carcinogenesis, HPV infection, and disease progression.

Complex regulatory networks influence pluripotent cell state transitions in human iPSCs.

Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Analyzing hundreds of hiPSCs derived from different individuals, we show the proportions of these pluripotent states vary considerably across lines. We discover 13 gene network modules (GNMs) and 13 regulatory network modules (RNMs), which are highly correlated with each other suggesting that the coordinated co-accessibility of regulatory elements in the RNMs likely underlie the coordinated expression of genes in the GNMs. Epigenetic analyses reveal that regulatory networks underlying self-renewal and pluripotency are more complex than previously realized. Genetic analyses identify thousands of regulatory variants that overlapped predicted transcription factor binding sites and are associated with chromatin accessibility in the hiPSCs. We show that the master regulator of pluripotency, the NANOG-OCT4 Complex, and its associated network are significantly enriched for regulatory variants with large effects, suggesting that they play a role in the varying cellular proportions of pluripotency states between hiPSCs. Our work bins tens of thousands of regulatory elements in hiPSCs into discrete regulatory networks, shows that pluripotency and self-renewal processes have a surprising level of regulatory complexity, and suggests that genetic factors may contribute to cell state transitions in human iPSC lines.

Does the Number of Comorbidities Predict Pain and Disability in Older Adults With Chronic Low Back Pain? A Longitudinal Study With 6- and 12-Month Follow-ups.

BACKGROUND AND PURPOSE: People who live longer often live with multimorbidity. Nevertheless, whether the presence of multimorbidity affects pain and disability in older adults with chronic low back pain (LBP) remains unclear. The aim of this study was to investigate whether multimorbidity predicts pain intensity and disability at 6- and 12-month follow-ups in older adults with chronic LBP. METHODS: This was a prospective, longitudinal study with 6- and 12-month follow-ups. Participants with chronic LBP (age ≥ 60 years) were recruited and interviewed at baseline, 6 months, and 12 months. Self-reported measures included the number of comorbidities, assessed through the Self-Administered Comorbidity Questionnaire, pain intensity, assessed with the 11-point Numerical Rating Scale, and disability, assessed with the Roland-Morris Disability Questionnaire. Data were analyzed using univariate and multivariate regression models. RESULTS AND DISCUSSION: A total of 220 participants were included. The number of comorbidities predicted pain intensity at 6-month (ß= 0.31 [95% CI: 0.12 to 0.50]) and 12-month (ß= 0.29 [95% CI: 0.08 to 0.50]) follow-ups. The number of comorbidities predicted disability at 6-month (ß= 0.55 [95% CI: 0.20 to 0.90]) and 12-month (ß= 0.40 [95% CI: 0.03 to 0.77]) follow-ups. CONCLUSION: The number of comorbidities at baseline predicted pain and disability at 6-month and 12-month follow-ups in older adults with chronic LBP. These results highlight the role of comorbidities as a predictive factor of pain and disability in patients with chronic LBP, emphasizing the need for timely and continuous interventions in older adults with multimorbidity to mitigate LBP-related pain and disability.

Machine learning for hospital readmission prediction in pediatric population.

BACKGROUND AND OBJECTIVE: Pediatric readmissions are a burden on patients, families, and the healthcare system. In order to identify patients at higher readmission risk, more accurate techniques, as machine learning (ML), could be a good strategy to expand the knowledge in this area. The aim of this study was to develop predictive models capable of identifying children and adolescents at high risk of potentially avoidable 30-day readmission using ML. METHODS: Retrospective cohort study was carried out with 9,080 patients under 18 years old admitted to a tertiary university hospital. Demographic, clinical, and biochemical data were collected from electronic databases. We randomly divided the dataset into training (75 %) and testing (25 %), applied downsampling, repeated cross-validation with five folds and ten repetitions, and the hyperparameter was optimized of each technique using a grid search via racing with ANOVA models. We applied six ML classification algorithms to build the predictive models, including classification and regression tree (CART), random forest (RF), gradient boosting machine (GBM), extreme gradient boosting (XGBoost), decision tree and logistic regression (LR). The area under the receiver operating curve (AUC), sensitivity, specificity, Youden's J-index and accuracy were used to evaluate the performance of each model. RESULTS: The avoidable 30-day hospital readmissions rate was 9.5 %. Some algorithms presented similar AUC, both in the dataset training and in the dataset testing, such as XGBoost, RF, GBM and CART. Considering the Youden's J-index, the algorithm that presented the best index was XGBoost with bagging imputation, with AUC of 0.814 (J-index of 0.484). Cancer diagnosis, age, red blood cells, leukocytes, red cell distribution width and sodium levels, elective admission, and multimorbidity were the most important characteristics to classify between readmission and non-readmission groups. CONCLUSION: Machine learning approaches, especially XGBoost, can predict potentially avoidable 30-day pediatric hospital readmission into tertiary assistance. If implemented in the computer hospital system, our model can help in the early and more accurate identification of patients at readmission risk, targeting health strategic interventions.

Simplesmente mães: construção compartilhada de tecnologias sobre pré-natal de mulheres com deficiência visual / Simply mothers: shared elaboration of technologies on prenatal care of visually impaired women / Simplemente madres: creación compartida de tecnologías sobre el control prenatal para mujeres con discapacidad visual

RESUMO Objetivo: Desenvolver tecnologias educacionais sobre pré-natal com e para mulheres deficientes visuais. Método: Estudo metodológico com interface participativa e abordagem qualitativa. Realizado em uma Unidade Técnica Especializada no município de Belém, Pará, Brasil. A produção de dados ocorreu entre agosto e setembro de 2021 com seis mulheres. Utilizou-se o DOSVOX como recurso de comunicação para que as participantes respondessem quatro instrumentos com vistas ao desenvolvimento das tecnologias. A análise foi de conteúdo temático. Resultados: As mulheres com deficiência visual querem respeito à sua autonomia, inclusão e informação dos profissionais. As tecnologias produzidas apontam as demandas específicas de mulheres com deficiência visual e a importância de preservar a autonomia durante a realização do pré-natal. Conclusão: Tecnologias produzidas de forma participativa apontam perspectivas e necessidades específicas das mulheres sobre o pré-natal e poderão subsidiar tanto o agir dos enfermeiros nas consultas como favorecer mulheres com deficiência visual durante o pré-natal.

ABSTRACT Objective: To develop educational technologies on prenatal care with and for visually impaired women. Method: A methodological study with a participatory interface and qualitative approach. It was carried out at a Specialized Technical Unit in the municipality of Belém, Pará, Brazil. Data production took place between August and September 2021 with six women. DOSVOX was used as a communication resource for the participants to answer four instruments with a view to developing the technologies. The analysis was of the thematic content type. Results: Women with visual impairment want respect for their autonomy, inclusion, and information from the professionals. The technologies produced point to the specific demands of visually impaired women and to the importance of preserving autonomy during prenatal care. Conclusion: Technologies produced in a participatory way point out women's specific perspectives and needs regarding prenatal care and may support both the nurses' actions in consultations and favor women with visual impairment during prenatal care.

RESUMEN Objetivo: Desarrollar tecnologías educativas sobre el control prenatal con y para mujeres con discapacidad visual. Método: Estudio metodológico con interfaz participativa y enfoque cualitativo. Realizado en una Unidad Técnica Especializada de la ciudad de Belém, Pará, Brasil. La producción de datos se realizó entre agosto y septiembre de 2021 con seis mujeres. Se utilizó DOSVOX como recurso de comunicación para que las participantes respondieran a cuatro instrumentos a fin de desarrollar las tecnologías. El análisis fue de contenido temático. Resultados: Las mujeres con discapacidad visual quieren que se respete su autonomía, inclusión e información por parte de los profesionales. Las tecnologías creadas ponen de manifiesto las demandas específicas de las mujeres con discapacidad visual y la importancia de preservar la autonomía durante el control prenatal. Conclusión: Las tecnologías creadas de manera participativa señalan las perspectivas y necesidades específicas de las mujeres con respecto al cuidado prenatal y pueden ayudar a los enfermeros en las consultas y a las mujeres con discapacidad visual durante el control prenatal.

Translation and cross-cultural adaptation of the "Protocolo de Avaliação Miofuncional Orofacial MBGR" from Brazilian Portuguese into English.

In health-related research, an increasing number of clinical assessment tools are translated and cross-culturally adapted for cross-national and cross-cultural studies and comparisons. However, when translating and cross-culturally adapting clinical assessment tools for use across new countries, cultures, or languages, we must follow a thorough method to reach semantic, idiomatic, experiential, and conceptual equivalences between translated and original versions. Therefore, in this study, we translated and cross-culturally adapted the Protocolo MBGR (Marchesan, Berretin-Felix, Genaro, and Rehder) from Brazilian Portuguese into English, following international guidelines, and named it "MBGR Protocol." To verify its content validity, we used the Content Validity Index. Results indicated excellent content validity: a Scale-Content Validity Index of 0.96 and 97% of all translation units with an Item-Content Validity Index of 1.00. Also, to prove its face validity and confirm whether it worked in the target population's linguistic-cultural setting, we used it with 35 subjects. Again, results demonstrated excellent face validity: in the pretest, 91% of all translation units were considered comprehensible and clear; in the pilot test, 98% of all translation units were considered comprehensible and clear. Thus, we concluded that the MBGR Protocol is promising to enhance the uptake of studies in Orofacial Myology worldwide and support researchers and health professionals in assessing and diagnosing orofacial myofunctional disorders in children, adolescents, adults, and the elderly. Also, it may support evidence-based practice and assist in standardizing assessment and diagnostic criteria. The MBGR Protocol should have its psychometric properties tested before being used in clinical practice or scientific research. Therefore, future studies are needed, and collaborations among researchers from South and North American countries are encouraged to create an international network and advance with knowledge and skills in the Orofacial Myology discipline.

G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. / Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão.

BACKGROUND: Central Illustration : G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. BACKGROUND: Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. OBJECTIVE: To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. METHOD: The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. RESULTS: The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). CONCLUSION: These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Effect of Dry Needling on Morphofunctional Capacity of Masticatory Muscles, and Bite Force in Patients with Temporomandibular Disorders of Muscular Origin / Efeito do Agulhamento a Seco na Capacidade Morfofuncional dos Músculos Mastigatórios e na Força de Mordida em Pacientes com Disfunções Temporomandibulares de Origem Muscular

The presence of myofascial trigger points in the masticatory muscles can lead to pain and may be related to temporomandibular dysfunction. The dry needling technique (DN) is employed for mechanical disruption and deactivation of trigger points in skeletal muscles. The purpose of this observational longitudinal clinical study was to determine the morphofunctional capacity of the masseter and temporalis muscles, and bite force in patients with temporomandibular disorders of muscular origin after DN of the masseter muscle. Twenty-one patients with the presence of trigger points in the masseter muscle were selected. Electromyographic activity of the masseter and temporalis muscles was assessed during the mandibular tasks of rest, protrusion, right and left laterality, and maximal voluntary contraction (MVC). Muscle thickness at rest and dental clenching at MVC was measured with ultrasound. Molar bite force (right and left) was analyzed with a digital dynamometer. Patients were evaluated before and seven days after intervention with DN. Data were subject to the paired t test for dependent samples (p<0.05). There was significant difference in the left masseter muscle in right laterality (p=0.01), right temporalis muscle thickness in MVC (p=0.05), and right (p=0.01) and left (p=0.008) molar bite force, after DN. The authors suggest that DN was efficient in the positive changes in the morphofunctional performance of the stomatognathic system. (AU)

A presença de pontos gatilhos miofasciais nos músculos mastigatórios pode gerar dor e estar relacionada à disfunção temporomandibular. A técnica de agulhamento a seco (AS) é utilizada para rompimento mecânico e desativação do ponto gatilho nos músculos esqueléticos. O objetivo deste estudo clínico longitudinal observacional foi determinar a capacidade morfofuncional dos músculos masseter e temporal, bem como a força de mordida, em pacientes com distúrbios temporomandibulares de origem muscular após AS no músculo masseter. Foram selecionados vinte e um pacientes com presença de pontos de gatilho no músculo masseter. A atividade eletromiográfica dos músculos masseter e temporal foi avaliada durante tarefas mandibulares de repouso, protrusão, lateralidade direita e esquerda, e contração voluntária máxima (CVM). A espessura muscular em repouso e a contração dental na CVM foram medidas por ultrassom. A força de mordida molar (direita e esquerda) foi analisada com um dinamômetro digital. Os pacientes foram avaliados antes e sete dias após a intervenção com DN. Os dados foram submetidos ao teste t pareado para amostras dependentes (p<0,05). Houve diferença significante no músculo masseter esquerdo na lateralidade direita (p=0,01), espessura do músculo temporal direito na CVM (p=0,05) e força de mordida molar direita (p=0,01) e esquerda (p=0,008), após AS. Os autores sugerem que o AS foi eficaz nas alterações positivas no desempenho morfofuncional do sistema estomatognático. (AU)

Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão / G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.

Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Retinol Levels and Severity of Patients with COVID-19.

The new coronavirus infection represents a serious threat to global health and economies. In this sense, it is paramount to know the nutritional factors that may be related to the prognosis of the disease. Evidence shows that vitamin A may play an important preventive and therapeutic role in supporting respiratory infections as in COVID-19. The aim of our study was to evaluate the association of vitamin A (retinol) status with the prognosis of the disease. A case-control study from a cohort study was conducted in Brazil between May and October 2020. The study population was chosen by convenience, consisting of participants diagnosed with COVID-19. Recruitment was carried out using different approaches, including through dissemination on social media and in four hospitals in the city of Natal/RN, Brazil, recruiting participants from the COVID-19 ward and hospitalized participants who tested positive for the disease. The participants were allocated into two groups according to severity, with a group of mild (n = 88) or critical (n = 106) patients and compared to a control group (selected before the pandemic, n = 46). The extraction of retinol serum was performed and analyzed using the high-performance liquid chromatography method (HPLC). The retinol level was calculated in mmol/L, and levels below 0.7 µmol/L (20 µg/dL) were considered to be a vitamin A deficiency. Our findings suggest that the participants with mild and critical COVID-19 had lower retinol levels compared to the healthy controls (p = 0.03). In addition, milder cases of COVID-19 were associated with increased symptoms and prolonged symptoms after 90 days since the beginning of infection. However, the survival analysis showed no association with higher cases of death among participants with vitamin A deficiency (p = 0.509). More studies are needed to understand how nutritional status, including vitamin A levels, can influence prognosis and is a risk factor for the development of long COVID syndrome.

The efficacy of neuromuscular training, with minimal or no equipment, on performance of youth athletes: A systematic review with meta-analysis.

OBJECTIVES: To investigate the effects of neuromuscular training, with minimal or no equipment, on physical performance of youth athletes. DESIGN: Systematic review with meta-analysis. METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, PEDro and SportDiscuss from inception to March/2022. SELECTION CRITERIA: youth athletes (15-24years), from Olympic team sports; used neuromuscular training 2-3 times/week for, at least, 6 weeks; had a control group/usual training group; physical performance as outcomes; randomized controlled trial. DATA SYNTHESIS: Pooled estimate of standardized mean difference (SMD), and 95% confidence interval (95%CI). RESULTS: Thirty-four studies (1111 participants) were included. Results showed that neuromuscular training improved power (SMD: 0.84 [95%CI: 0.58, 1.10]; n = 805; I2 = 64%), speed (SMD: -1.12 [95%CI: -1.68, -0.57]; n = 688; I2 = 90%) and agility (SMD: -1.21 [95%CI: -1.60, -0.83]; n = 571; I2 = 76%) compared to control group, but showed no difference between groups for muscle strength (Quadriceps SMD: 0.34 [95%CI: -0.02, 0.69]; n = 132; I2 = 0%, Hamstrings: SMD: 0.64 [95%CI: -0.04, 1.33]; n = 132; I2 = 71%), balance and flexibility. CONCLUSION: Clinically, neuromuscular training with minimal equipment may be useful for teams with limited resources to improve mainly athletes' power and agility, including those interventions that were designed to injury prevention. Future high-quality studies are likely to change these estimates.

Clinical trial registration has become more prevalent in physical therapy but it is still inadequate: A meta-research study.

BACKGROUND: A study using data from 2009 showed low prevalence and inadequate trial registration in physiotherapy. In 2013, a joint editorial recommended prospective registration in physiotherapy journals. Ten years later it is unclear whether the joint editorial achieved its intended benefit. OBJECTIVES: To investigate the proportion of randomized trials adequately registered and the extent of selective reporting of outcomes in trials of physiotherapy interventions published in 2019 and to compare these data with equivalent published data from 2009. DESIGN: Meta-research study. METHOD: A random sample of 200 trials published in 2019 was used. Evidence of registration was sought on trial registers and by contacting authors. Data from the article was compared with data from the trial registration. Data from this sample of trial published in 2019 were compared with equivalent published data from 2009. RESULTS: In 2019, the proportion of trials that were registered was 63% versus 34% in 2009 (absolute difference 29%). In 2019, 18% of the trials were prospectively registered compared to 6% in 2009 (absolute difference 12%). Unambiguous primary outcomes (i.e., method and timepoints of measurement clearly defined in the trial registry entry) were registered for 30% in 2019. Registration was adequate (i.e., prospective with unambiguous primary outcomes) for 8%, compared with 3% in 2009 (absolute difference 5%). Selective outcome reporting occurred in 73% of the trials in which it was assessable; in 2009 this proportion was 47% (absolute difference 26%). CONCLUSIONS: Registration of randomized trials in physiotherapy increased in the past decade, but it is still inadequate. More effort is still required to implement and enforce adequate registration.

Post-Covid condition and clinic characteristics associated with SARS-CoV-2 infection: a 2-year follow-up to Brazilian cases.

Until January 2023, Brazil recorded 37 million COVID-19 cases despite the decrease in mortality due to mass vaccination efforts against COVID-19. The infection continues to challenge researchers and health professionals with the persistent symptoms and onset manifestations after the acute phase of the disease, namely Post-Covid Condition (PCC). Being one of the countries with the highest infection rate, Brazil must prepare for a growing number of patients with chronic health consequences of COVID-19. Longitudinal studies that follow patients over extended periods are crucial in understanding the long-term impacts of COVID-19, including potential health consequences and the effects on quality of life. We describe the clinical profile of a cohort of COVID-19 patients infected during the first year of the pandemic in Brazil and a follow-up after two years to investigate the health impacts of SARS-CoV-2 infection. The first wave of SARS-CoV-2 infection in Brazil featured extensive drug misuse, notably the ineffective COVID kit comprised of ivermectin, antimalarials and azithromycin, and elevated in-hospital mortality. In the second phase of the study, Post-Covid Condition was reported by symptomatic COVID-19 subjects across different severity levels two years after infection. Long haulers are more likely to be women, previously hospitalized, and reported a range of symptoms from muscle pain to cognitive deficit. Our longitudinal study is essential to inform public health authorities to develop strategies and policies to control the spread of the virus and mitigate its impacts on society.