The importance of the location of the N-terminus in successful protein folding in vivo and in vitro.

Protein folding in the cell often begins during translation. Many proteins fold more efficiently cotranslationally than when refolding from a denatured state. Changing the vectorial synthesis of the polypeptide chain through circular permutation could impact functional, soluble protein expression and interactions with cellular proteostasis factors. Here, we measure the solubility and function of every possible circular permutant (CP) of HaloTag in Escherichia coli cell lysate using a gel-based assay, and in living E. coli cells via FACS-seq. We find that 78% of HaloTag CPs retain protein function, though a subset of these proteins are also highly aggregation-prone. We examine the function of each CP in E. coli cells lacking the cotranslational chaperone trigger factor and the intracellular protease Lon and find no significant changes in function as a result of modifying the cellular proteostasis network. Finally, we biophysically characterize two topologically interesting CPs in vitro via circular dichroism and hydrogen-deuterium exchange coupled with mass spectrometry to reveal changes in global stability and folding kinetics with circular permutation. For CP33, we identify a change in the refolding intermediate as compared to wild-type (WT) HaloTag. Finally, we show that the strongest predictor of aggregation-prone expression in cells is the introduction of termini within the refolding intermediate. These results, in addition to our finding that termini insertion within the conformationally restrained core is most disruptive to protein function, indicate that successful folding of circular permutants may depend more on changes in folding pathway and termini insertion in flexible regions than on the availability of proteostasis factors.

Association between multimorbidity and hospitalization in older adults: systematic review and meta-analysis.

BACKGROUND: Multimorbidity is defined as the presence of multiple chronic conditions in the same individual. Multimorbidity is more prevalent in older adults and can lead to several adverse health outcomes. METHODS: We systematically reviewed evidence from observational studies to verify the association between multimorbidity and hospitalization in older adults. Furthermore, we also aimed to identify whether it changes according to gender, advanced age, institutionalization, and wealth of the country of residence. We searched the PubMed, Embase and Scopus databases from December 2020 to April 2021. The analysed outcomes were as follows: hospitalization, length of stay and hospital readmission. RESULTS: Of the 6,948 studies identified in the databases, 33 were included in this review. From the meta-analysis results, it was found that multimorbidity, regardless of the country's wealth, was linked to hospitalization in older adults (OR = 2.52, CI 95% = 1.87-3.38). Both definitions of multimorbidity, ≥2 (OR = 2.35, 95% CI = 1.34-4.12) and ≥3 morbidities (OR = 2.52, 95% CI = 1.87-3.38), were associated with hospitalization. Regardless of gender, multimorbidity was associated with hospitalization (OR = 1.98, 95% CI = 1.67-2.34) and with readmission (OR = 1.07, 95% CI = 1.04-1.09). However, it was not possible to verify the association between multimorbidity and length of stay. CONCLUSIONS: Multimorbidity was linked to a higher hospitalization risk, and this risk was not affected by the country's wealth and patient's gender. Multimorbidity was also linked to a higher hospital readmission rate in older adults. PROSPERO Registration (Registration number: CRD42021229328).

Pain in Patients With Chronic Kidney Disease Undergoing Hemodialysis: A Systematic Review.

AIMS: To assess the presence of pain, its location, intensity, and effects on the daily activities of patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). PARTICIPANTS/SUBJECTS: Patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). DESIGN: A systematic review. METHODS: We carried out search for articles published until December 2020, including publications in Portuguese, English, and Spanish during the past 15 years (2005-2020), using the Embase, SciELO, PubMed, and Web of Science databases. The following information was collected: type of pain, pain treatment, pain assessment instrument, prevalence of pain, location, and influence of pain on quality of life. RESULTS: Twenty-five studies were selected for a systematic review. These studies involved a total of 98,162 adult and elderly patients with CKD who were undergoing HD. There was a high prevalence of pain in patients with CKD on HD. The most frequent sites of pain were the head, back, bones, chest, and the upper and lower limbs. The presence of acute, chronic, neuropathic pain, and myalgia was also reported in the studies. In addition, there was a higher frequency of moderate and severe pain, which influenced daily activities, the ability to walk, mood, relationships with other people, sleep, and work in patients on dialysis. CONCLUSIONS: The analyzed studies suggest that acute and chronic pain is a prevalent complaint in adults and elderly patients undergoing HD. There was a higher frequency of moderate and severe pain in different parts of the body, and pain interfered with everyday activities.

[Mapping the implementation characteristics of new Medicine programs in Brazilian federal universitiesMapeo de las características de implementación de los nuevos programas de medicina en universidades federales brasileñas]. / Mapeamento das características da implantação de novos cursos de Medicina em universidades federais brasileiras.

OBJECTIVE: To map the implementation characteristics of Medicine programs established in Brazilian federal universities from 2013 onwards. METHODS: A qualitative and quantitative exploratory study was performed. Newly created Medicine programs were identified in federal universities, with analysis of pedagogical frameworks and interviews with students, faculty, and health care professionals from associated health care services. Data were analyzed using qualitative and quantitative methods. RESULTS: Thirty new Medicine programs were identified, of which 24 were visited. All the new programs were located outside large urban centers and capitals, across the five Brazilian macro-regions, and adopted various formative configurations in an attempt to overcome fragmentation of content with active methodologies and formative evaluations. The healthcare network is used for training as a means to meet the challenge of academic-health service-community integration, with the aim of providing critical education focused on public health. The establishment of the Medicine programs facilitated to a limited extent the retention of faculty in remote areas and promoted the access of local students and the creation of residency programs, which are powerful strategies to enhance the retention of medical professionals. CONCLUSIONS: Variations were observed among the programs in the manner of implementation and adherence to the National Curriculum Guidelines for Medicine, published in 2014. The construction of medical training models that appropriately address local specificities and the requirements of the Unified Health System in its formative role for health care may contribute to reduce health inequalities.

OBJETIVO: Mapear las características de implementación de los programas de Medicina establecidos en las universidades federales brasileñas a partir de 2013. MÉTODOS: Se realizó un estudio exploratorio cualitativo y cuantitativo. Se identificaron los programas de medicina recién creados en las universidades federales, se anlizaron los marcos pedagógicos y se entrevistaron estudiantes, profesores y profesionales de la salud de los servicios de salud asociados. Los datos fueron analizados usando métodos cualitativos y cuantitativos. RESULTADOS: Se identificaron 30 nuevos programas de medicina, de los cuales se visitaron 24. Todos los nuevos programas se ubicaron fuera de los grandes centros urbanos y capitales en las cinco macrorregiones brasileñas y adoptaron diversas configuraciones formativas en un intento de superar la fragmentación de contenido con metodologías activas y evaluaciones formativas. La red de salud se empleó para la formación como un medio para facilitar la integración entre los ámbitos académico, de servicios de salud y la comunidad, con el objetivo de proporcionar una educación crítica centrada en la salud pública. El establecimiento de los programas de medicina facilitó en cierta medida la retención del profesorado en zonas remotas y promovió el acceso de los estudiantes locales y la creación de programas de residencia, que son estrategias importantes para mejorar la retención de los profesionales médicos. CONCLUSIONES: Se observaron variaciones entre los programas en cuanto a la manera de aplicar y cumplir las Directrices Curriculares Nacionales de Medicina, publicadas en 2014. La construcción de modelos de formación médica que aborden adecuadamente las especificidades locales y los requisitos del Sistema Único de Salud en su función formativa para la atención de la salud puede contribuir a reducir las desigualdades en materia de salud.

Folding and binding pathways of BH3-only proteins are encoded within their intrinsically disordered sequence, not templated by partner proteins.

Intrinsically disordered regions are present in one-third of eukaryotic proteins and are overrepresented in cellular processes such as signaling, suggesting that intrinsically disordered proteins (IDPs) may have a functional advantage over folded proteins. Upon interacting with a partner macromolecule, a subset of IDPs can fold and bind to form a well-defined three-dimensional conformation. For example, disordered BH3-only proteins bind promiscuously to a large number of homologous BCL-2 family proteins, where they fold to a helical structure in a groove on the BCL-2-like protein surface. As two protein chains are involved in the folding reaction, and the structure is only formed in the presence of the partner macromolecule, this raises the question of where the folding information is encoded. Here, we examine these coupled folding and binding reactions to determine which component determines the folding and binding pathway. Using Φ value analysis to compare transition state interactions between the disordered BH3-only proteins PUMA and BID and the folded BCL-2-like proteins A1 and MCL-1, we found that, even though the BH3-only protein is disordered in isolation and requires a stabilizing partner to fold, its folding and binding pathway is encoded in the IDP itself; the reaction is not templated by the folded partner. We suggest that, by encoding both its transition state and level of residual structure, an IDP can evolve a specific kinetic profile, which could be a crucial functional advantage of disorder.

Disorder drives cooperative folding in a multidomain protein.

Many human proteins contain intrinsically disordered regions, and disorder in these proteins can be fundamental to their function-for example, facilitating transient but specific binding, promoting allostery, or allowing efficient posttranslational modification. SasG, a multidomain protein implicated in host colonization and biofilm formation in Staphylococcus aureus, provides another example of how disorder can play an important role. Approximately one-half of the domains in the extracellular repetitive region of SasG are intrinsically unfolded in isolation, but these E domains fold in the context of their neighboring folded G5 domains. We have previously shown that the intrinsic disorder of the E domains mediates long-range cooperativity between nonneighboring G5 domains, allowing SasG to form a long, rod-like, mechanically strong structure. Here, we show that the disorder of the E domains coupled with the remarkable stability of the interdomain interface result in cooperative folding kinetics across long distances. Formation of a small structural nucleus at one end of the molecule results in rapid structure formation over a distance of 10 nm, which is likely to be important for the maintenance of the structural integrity of SasG. Moreover, if this normal folding nucleus is disrupted by mutation, the interdomain interface is sufficiently stable to drive the folding of adjacent E and G5 domains along a parallel folding pathway, thus maintaining cooperative folding.

[Importance of local management for delivery of primary health care according to Alma-Ata principlesImportancia de la gestión local para una atención primaria de salud según las propuestas de Alma-Ata]. / Importância do gerenciamento local para uma atenção primária à saúde nos moldes de Alma-Ata.

OBJECTIVE: To describe the characteristics of the management process in primary health care units as well as the profile of managers, and to discuss the implications of these elements for the attainment of Unified Health System principles in Brazil in accordance with the propositions of the Alma-Ata Declaration. METHOD: This descriptive, cross-sectional study used data collected with the Primary Care Service Quality Assessment tool (QualiAB), a self-administered, web-based instrument. QualiAB was voluntarily answered by 157 unit managers from 41 municipalities in the state of São Paulo from October to December 2014. RESULTS: Of 157 units, 67 (42.7%) were family health care units and 58 (36.9%) were "traditional" units; 95 (60.5%) were located in urban peripheries. At the time of the study, eight (5.0%) units did not have a manager and eight (5.0%) were managed by the city health secretary. Almost 80% of the managers were nurses and performed multiple tasks in addition to management. Multidisciplinary support (technical supervision as a means of continuing education) was available in 75 (47.7%) units; 60 (38.2%) units did not have any kind of multidisciplinary support. Participation in evaluative processes was mentioned in 130 (82.8%) units. The main results of evaluations were planning and reprogramming of activities with the engagement of the multiprofessional team in 40 units (25.5%) and definition of an annual activity plan in 38 (24.2%). Twenty-nine units (17.8%) did not have access to the results of evaluations. CONCLUSION: The study supports the importance of work process management and the need to (re)invest in training and recognition of local management as a strategy to produce primary health care that is capable of promoting health as a right and a condition of citizenship.

OBJETIVO: Describir las características de la gestión de las unidades de atención primaria de salud y el perfil de los gerentes, y analizar las implicaciones de esos elementos en la puesta en práctica de los principios del Sistema Único de Salud de Brasil de forma coherente con las propuestas de Alma- Ata. MÉTODOS: Estudio descriptivo, transversal, con datos recolectados a través del cuestionario de Evaluación de la Calidad de Servicios de Atención Básica (QualiAB), un instrumento autoadministrado a través de Internet. En total 157 gerentes de Unidades Básicas de Salud de 41 municipios del estado de São Paulo respondieron voluntariamente el QualiAB entre octubre y diciembre de 2014. RESULTADOS: De las 157 unidades, 67 (42,7%) eran unidades salud de la familia y 58 (36,9%) eran unidades básicas de salud de organización "tradicional"; 95 (60,5%) estan ubicadas en una región urbana periférica. En el momento del estudio, ocho (5,0%) unidades no poseían gerente y ocho (5,0%) eran gestionadas por secretarios municipales de salud. Casi el 80% de los gerentes eran enfermeros y desempeñaban múltiples funciones además de la gerencia. En 75 (47,7%) unidades se disponía de apoyo multidisciplinario (supervisión técnica como forma de educación permanente); 60 (38,2%) unidades no contaban con ningún tipo de apoyo multidisciplinario. La participación en procesos de evaluación fue referida por 130 (82,8%) servicios. Las principales modificaciones inducidas por las evaluaciones fueron la planificación y reprogramación de las actividades con participación del equipo multiprofesional en 40 unidades (25,5%) y la definición de un plan anual de actividades en 38 (24,2%). No tuvieron acceso a los resultados de las evaluaciones 29 unidades (17,8%). CONCLUSIÓN: El estudio subraya la importancia de la gestión del trabajo y la necesidad de reinvertir en la formación y valorización de la gestión local como estrategia para hacer efectiva una atención primaria de salud capaz de promover la salud como derecho y condición de ciudadanía.

Determinants of eating patterns and nutrient intake among adolescent athletes: a systematic review.

BACKGROUND: This review aims to update the influences of sport modalities, sport performance, and non-exercise-related determinant, on eating patterns and nutrient intake outcomes among adolescent competitive athletes. METHODS: The PubMed and Scopus databases were searched for the last 20 years. Observational and intervention studies of all languages on eating patterns and nutrient intake in adolescent (10- to 19-year-old) competitive athletes were included. Study quality and risk of bias were assessed using a Downs and Black instrument. Moreover, the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) evidence system was used to assess the strength of the body of evidence. RESULTS: Regarding outcomes of 21 included articles, 95.2% of studies focused on nutrient analysis, whereas few of the included articles reported eating patterns. As determinants, most studies analyzed the influences of sport-related (n = 10) and demographic factors (n = 8), among which only sport modalities were significantly associated with nutrient intake. Age and sex were not significantly associated with nutrient intake. All studies were observational, and most were cross-sectional (n = 17) and conducted in developed countries such as the United States and European nations. Most studies evaluated boys, and the sport that received the most attention was soccer. CONCLUSIONS: Athletes do not adjust their nutrient intake or food choice to the demands of the training load or different training sessions, while sport modalities significantly influenced nutrient intake. Moreover, results concerning demographic determinants were inconsistent and thus remain inconclusive. TRIAL REGISTRATION: Prospero CRD42016043310 .

Primary health care organization in municipalities of São Paulo, Brazil: a model of care aligned with the Brazilian Unified National Health System's guidelines. / Organização da atenção primária à saúde de municípios de São Paulo, Brasil: modelo de atenção e coerência com as diretrizes do Sistema Único de Saúde.

This study analyzes the main organization patterns used by primary health care (PHC) services in municipal networks and evaluates them according to indicators of local management-administration interface. Evaluative research analyzed 461 municipalities in São Paulo, Brazil, that participated in the Primary Care Services Quality Assessment Survey (QualiAB) in 2017/2018, classified according to the organizational arrangements composition of 2,472 PHC services. Eight indicators of local management and administration were selected to evaluate the identified patterns. Results indicate two groups of municipalities: homogeneous, with services presenting the same arrangement (43.6%); and heterogeneous, with different arrangements (56.4%). These were subdivided into seven patterns that ranged from homogeneous-traditional, homogeneous-Family Health Strategy, homogeneous-mixed, and different combinations in the heterogeneous group. All indicators showed significant differences between groups (p < 0.001), especially the homogeneous-traditional group, which presented an organizational pattern far from the desired model of a comprehensive and problem-solving PHC. Those integrated with family health units (FHU) and basic health units with community health workers and/or family health teams (BHU/FHU) showed a pattern closer to a comprehensive model - with planning and evaluation actions committed to the local reality and qualification of care. Implementation of federal and state policies are essential for defining the PHC health care model adopted by municipalities.

Este trabalho tem como objetivo analisar os principais padrões de organização das redes municipais de serviços de atenção primária à saúde (APS) e avaliá-los segundo os indicadores de interface entre gestão e gerenciamento local. Trata-se de pesquisa avaliativa que analisou 461 municípios de São Paulo, Brasil, que participaram do Inquérito de Avaliação da Qualidade de Serviços de Atenção Básica (QualiAB) em 2017/2018, classificados segundo a composição dos arranjos organizacionais de 2.472 serviços de APS. Para avaliar os padrões identificados, foram selecionados oito indicadores de gestão e gerenciamento local. Os resultados apontam dois grupos de municípios: homogêneos, com serviços de um mesmo arranjo (43,6%); e heterogêneos, com diferentes arranjos (56,4%). Os grupos foram subdivididos em sete padrões que variaram entre homogêneo-tradicional, homogêneo-Estratégia Saúde da Família, homogêneo-misto e diferentes combinações no grupo heterogêneo. Todos os indicadores apontaram diferenças significativas entre os grupos (p < 0,001), com destaque para o grupo homogêneo-tradicional, com padrão organizacional distante do modelo desejado para uma APS abrangente e resolutiva, enquanto aqueles com unidades de saúde da família (USF), e com unidades básicas com agentes comunitários de saúde e/ou equipes de saúde da família (UBS/USF) demonstraram um padrão mais aproximado desse modelo - com ações de planejamento e avaliação comprometidos com a realidade local e com a qualificação do trabalho. Discute-se a importância das políticas implementadas pela gestão federal e estadual e seu poder de indução na definição do modelo de atenção à saúde na APS dos municípios.

El trabajo tiene el objetivo de analizar los principales patrones de organización de las redes municipales de servicios de atención primaria de salud (APS) y evaluarlos conforme los indicadores de interfaz entre la dirección y gestión local. Se trata de una investigación evaluativa que analizó 461 municipios de São Paulo, Brasil, que participaron de la Encuesta de Evaluación de la Calidad de los Servicios de Atención Primaria (QualiAB) en 2017/2018, clasificados según la composición de los arreglos organizativos de 2.472 servicios de APS. Para evaluar los patrones identificados, se seleccionaron ocho indicadores de dirección y gestión local. Los resultados indican dos grupos de municipios: homogéneos, con servicios de un mismo arreglo (43,6%) e heterogéneos, con arreglos diferentes (56,4%). Los grupos se subdividieron en siete patrones que iban desde homogéneo-tradicional, homogéneo-Estrategia de Salud de la Familia, homogéneo-mixto y diferentes combinaciones en el grupo heterogéneo. Todos los indicadores señalaron diferencias significativas entre los grupos (p < 0,001), con destaque para el grupo homogéneo-tradicional, con patrón organizativo alejado del modelo deseado para una APS completa y resolutiva, mientras aquellos con unidades de salud de la familia (USF), y con unidades básicas con agentes comunitarios de salud y/o equipos de salud de la familia (UBS/USF) demostraron un patrón más cercano a este modelo -con acciones de planificación y evaluación comprometidas con la realidad local y con la calificación del trabajo. Se discute la importancia de las políticas implementadas por la gestión federal y la gestión estatal y su poder de inducción para definir el modelo de atención a la salud en la APS de los municipios.

Disability prevention, detection and assistance in primary health care services in the state of São Paulo, Brazil. / Prevenção, detecção e assistência à deficiência em serviços de atenção primária à saúde do Estado de São Paulo, Brasil.

The objective of this study was to assess the performance of primary health care (PHC) services for disability prevention, detection and assistance in the state of São Paulo. The study included 2739 health services, from 514 municipalities. 128 organizational quality indicators of the QualiAB instrument referring to the evaluative dimension "Attention to disability in primary health care services". The association of health care performance score of each domain with independent variables, health assessment, and support network were tested using of multiple linear regression. The performance percentage was 61.6% for all domains, 73.6% for structure (inputs and human resources), 68.7% for qualification of prenatal care, 56.1% for qualification of child health care, 55.8% for prevention of disabilities related to chronic conditions, and 53.9% for attention to people with disabilities and caregivers. There was a significant association with variables related to the type of service and participation in service evaluations. PHC services still perform incipient actions for the prevention, surveillance and diagnosis of disabilities as well as for comprehensive care for people with disabilities.

O objetivo do trabalho consiste em avaliar o desempenho de serviços de atenção primária à saúde (APS) do estado de São Paulo para prevenção, detecção e assistência à deficiência. Realizou-se uma pesquisa avaliativa em 2.739 serviços de saúde em 514 municípios com 128 indicadores da qualidade organizacional do instrumento QualiAB referentes à dimensão avaliativa "Atenção à deficiência em serviços de atenção primária à saúde". Foram utilizadas medidas de desempenho e associações entre os escores de cada domínio e variáveis independentes sobre planejamento, avaliação em saúde e rede de apoio, por meio de regressão linear múltipla. O percentual de desempenho para a dimensão foi de 61,6%, para o domínio estrutura (insumos e recursos humanos), 73,6%, para qualificação da atenção ao pré-natal, 68,7%, qualificação da atenção à saúde da criança, 56,1%, prevenção de incapacidades relacionadas a condições crônicas, 55,8%, e atenção à pessoa com deficiência e ao cuidador, 53,9%. Houve associação significativa com variáveis relacionadas ao tipo de serviço e de participação em avaliações de serviços. Os serviços de APS ainda realizam ações incipientes para prevenção, vigilância e diagnóstico das deficiências, assim como para a atenção integral a pessoas com deficiência.

Congenital syphilis: performance of primary care services in São Paulo, 2017.

OBJECTIVE: To evaluate congenital syphilis prevention actions in primary health care services in the state of São Paulo. METHODS: Cross-sectional evaluative research that used indicators extracted from the Survey of Evaluation and Monitoring of Primary Care Services ( Avaliação e Monitoramento de Serviços da Atenção Básica - QualiAB) in the state of São Paulo in 2017. An evaluative matrix composed of 31 indicators of prevention of congenital syphilis, categorized into four domains of analysis: diagnosis and treatment of acquired syphilis (10); basic infrastructure and resources (7); prevention of congenital syphilis during prenatal care (7); and educational actions and prevention of sexually transmitted infections (7). The frequency of services with positive responses for each indicator and the percentage of service performance were calculated based on the proportion of indicators reported per service and the overall average observed. Subsequently, services were classified into four quality groups, and associations between groups and each indicator, type of organizational arrangement and location were estimated. RESULTS: 2,565 services participated, located in 503 municipalities, with an overall average performance of 74.9%. The domain "diagnosis and treatment of acquired syphilis" had the highest performance (89.8%), followed by "infrastructure and basic resources" (79.5%), "prevention of congenital syphilis in prenatal care" (73.3%) and "educational actions and prevention of sexually transmitted infections" (56.8%). There was a significant difference between quality groups and all indicators and types of organizational arrangements. CONCLUSIONS: The evaluated services have limitations in the development of actions to prevent congenital syphilis, mainly related to health education and actions included in prenatal care, such as screening and adequate treatment of pregnant women and their partners. Changes are needed in the work process, with the expansion of educational and surveillance actions, as well as the qualification of the teams to effectively comply with the protocols.

Relationship between depression and quality of life among students: a systematic review and meta-analysis.

The objectives of this systematic review were to estimate the prevalence of depression and to identify the relationship between depression and quality of life (QOL) among high school and university students. Literature search was performed in the Scopus, Embase, PubMed, Scielo, CINAHL and Web of Science databases, following the PRISMA methodology. The results were presented through descriptive approaches and meta-analysis. Thirty-six studies met the eligibility criteria, and twenty-six were included in the meta-analysis. The prevalence of depressive symptoms was 27% (95% CI 0.21-0.33) among students, being high school and university students was 25% (95% CI 0.14-0.37) and 27% (95% CI 0.20-0.34), respectively, and most studies have shown that depression was associated with low QOL. Among the limitations of the study is the difficulty of generalizing the results found, considering the large sample of health students. New studies should be conducted considering the severity, duration, and patterns of depressive symptoms in high school and university students, to better understand the relationship between depression and QOL.

Prevalence and Risk Factors of Musculoskeletal Disorders in Basketball Players: Systematic Review and Meta-Analysis.

Musculoskeletal disorders characteristically induce pain and limitations in mobility, ability, and overall functioning. In athletes, including basketball players, disorders such as back pain, postural changes, and spinal injuries are common. This systematic review aimed to evaluate the prevalence of back pain and musculoskeletal disorders in basketball players and ascertain the associated factors. Methods: The Embase, PubMed, and Scopus databases were searched for studies published in English without a time limit. Using STATA, meta-analyses were performed to estimate the prevalence of pain and musculoskeletal disorders of the back and spine. Results: Of the 4135 articles identified, 33 studies were included in this review, with 27 studies included in the meta-analysis. Of these, 21 were used for the meta-analysis of back pain, 6 articles were used for the meta-analysis of spinal injury, and 2 studies were used for the meta-analysis of postural changes. The overall prevalence of back pain was 43% [95% CI, -1% to 88%]; of these, the prevalence of neck pain was 36% [95% CI, 22-50%], the prevalence of back pain was 16% [95% CI, 4-28%], the prevalence of low back pain was 26% [95% CI, 16-37%], the prevalence of thoracic spine pain was 6% [95% CI, 3-9%]. The combined prevalence of spinal injury and spondylolysis was 10% [95% CI, 4-15%], with a prevalence of spondylolysis of 14% [95% CI, 0.1-27%]. The combined prevalence of hyperkyphosis and hyperlordosis was 30% [95% CI, 9-51%]. In conclusion, we found a high prevalence of neck pain, followed by low back pain and back pain, in basketball players. Thus, prevention programs are important to improve health and sports performance.

Prognostic Impact of AGR3 Protein Expression in Breast Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the clinicopathological significance and prognosis of the expression of the anterior gradient 3 (AGR3) protein in women with breast cancer. DATA SOURCES: The PubMed, CINAHL, EMBASE, Scopus, and Web of Science databases were searched for studies published in English and without restrictions regarding the year of publication. The search terms were: breast cancer AND anterior gradient 3 OR AGR3 expression. STUDY SELECTION: We included observational or interventional studies, studies on AGR3 protein expression by immunohistochemistry, and studies on invasive breast cancer. Case reports, studies with animals, and reviews were excluded. In total, 4 studies were included, containing 713 cases of breast cancer. DATA COLLECTION: Data were extracted on clinicopathological characteristics and survival. A meta-analysis of the prevalence of AGR3 expression was performed according to the clinicopathological characteristics, hazard ratios (HRs), and overall survival and disease-free survival. DATA SYNTHESIS: The expression of AGR3 was found in 62% of the cases, and it was associated with histological grade II, positivity of estrogen and progesterone receptors, low expression of ki67, recurrence or distant metastasis, and lumen subtypes. In patients with low and intermediate histological grades, AGR3 expression was associated with worse overall survival (HR: 2.39; 95% confidence interval [95%CI]: 0.628-4.159; p = 0.008) and worse disease-free survival (HR: 3.856; 95%CI: 1.026-6.686; p = 0.008). CONCLUSION: The AGR3 protein may be a biomarker for the early detection of breast cancer and predict prognosis in luminal subtypes. In addition, in patients with low and intermediate histological grades, AGR3 protein expression may indicate an unfavorable prognosis in relation to survival.

OBJETIVO: Investigar o significado clinicopatológico e prognóstico da expressão da proteína anterior gradient 3 (AGR3) em mulheres com câncer de mama. FONTES DE DADOS: Utilizamos as bases de dados PubMed, CINAHL, EMBASE, Scopus e Web of Science para pesquisar estudos em inglês, sem restrições quanto ao ano de publicação. Os termos buscados foram: breast cancer AND anterior gradient 3 OR AGR3 expression. SELEçãO DOS ESTUDOS: Foram incluídos estudos observacionais ou intervencionais, estudos sobre a expressão da proteína AGR3 por imuno-histoquímica, e estudos sobre câncer de mama invasivo. Excluíram-se relatos de casos, estudos com animais e revisões. Quatro estudos foram selecionados, que continham 713 casos de câncer de mama. COLETA DE DADOS: Foram extraídos dados relativos a características clinicopatológicas e sobrevida. A metanálise da prevalência da expressão de AGR3 foi realizada conforme as características clinicopatológicas, razões de risco (RRs) e sobrevida global (SG) e sobrevida livre de doença (SLD). SíNTESE DOS DADOS: Encontrou-se expressão de AGR3 em 62% dos casos, que se associou com grau histológico II, positividade de receptores de estrogênio e progesterona, baixa expressão de ki67, recorrência ou metástase à distância e subtipos luminais. Em pacientes com graus histológicos baixo e intermediário, a expressão de AGR3 conferiu pior SG (RR: 2,39; intervalo de confiança de 95% [IC95%]: 0,628­4,159; p = 0,008) e pior SLD (RR: 3,856; IC95%: 1,026­6,686; p = 0,008). CONCLUSãO: A AGR3 pode ser um biomarcador para a detecção precoce do câncer de mama e predizer o prognóstico em subtipos luminais. Em graus histológicos baixo e intermediário, a expressão da proteína AGR3 pode indicar um prognóstico desfavorável em relação à sobrevida.

Indicators of Eating Disorders in Sexually Abused Brazilian Adolescents: Family and School Contexts.

Eating disorders, characterized by abnormal eating behaviors, are among a wide variety of psychiatric conditions that mainly affect children and adolescents. These disorders have a multifactorial origin and can be associated with restrictive diets, negative feelings, harmful family relationships, and post-traumatic stress. Thus, this study's objective was to evaluate the association between indicators of eating disorders and family and school contexts in Brazilian adolescents who previously experienced sexual abuse and examine the findings based on sex. National School Health Survey data were utilized. Among 102,301 students between 11 and 19 years of age, 4124 reported having experienced sexual abuse and were included in this study. Self-report questionnaires were used to assess participants' health status and the presence of risk behaviors, which were examined through multivariate analysis using a Poisson regression model. The results indicated positive relationships between self-induced vomiting, laxative misuse, and other purgative methods and infrequent meals with family, hunger, and the presence of violence in students' daily lives, regardless of sex (p < 0.05). In addition, body dissatisfaction and negative feelings about one's body were associated with having been bullied or teased by schoolmates for both sexes (p < 0.05). Distant relationships with parents were associated with purgative methods and body dissatisfaction among female students (p < 0.05). In conclusion, body dissatisfaction, negative feelings about one's body, laxative misuse, self-induced vomiting, and purgative methods were found to be associated with factors in family and school contexts such as hunger, infrequent meals with family, family violence, distant relationships with parents, and bullying at school in adolescents who have previously experienced sexual abuse.

Motor performance and back pain in children and adolescents: A systematic review.

BACKGROUND AND OBJECTIVE: Motor performance during childhood and adolescence is recognized as a relevant determinant of present and future health, but its effects on back pain (BP) remain unclear. In this systematic review, we aimed to identify the association between motor performance and BP in children and adolescents. DATABASES AND DATA TREATMENT: A literature search was performed in the MEDLINE, Scopus, Embase, SPORTDiscus and CINAHL databases. We included cross-sectional, cohort, case-control and controlled clinical trials (data from control groups). The inclusion criteria were as follows: (a) participants aged 6-19 years; (b) assessment motor performance components; (c) assessment of BP and (d) reported measures of association. The risk of bias was assessed by the Downs and Black instrument and the quality of evidence by the grading of recommendations, assessment, development and evaluation (GRADE). RESULTS: A total of 2360 articles were identified, 25 of which were included in our systematic review. Of the 25 studies, 19 were evaluated as having a low risk of bias. GRADE indicated that 20 studies presented low or very low quality. Most of the studies evaluated flexibility (n = 16), muscle endurance (n = 18) and muscle strength (n = 9). Aerobic capacity, balance and speed were also examined in some studies (n < 5). Overall, motor performance (flexibility, muscle endurance, muscle strength, aerobic capacity, balance and speed) was not associated with BP. Most of the results were inconsistent because of the lack of studies, risk of bias and low quality of evidence. Only trunk extensor muscle endurance was associated with decreased BP with moderate quality of the supporting evidence. Prospective studies with a low risk of bias are warranted to further clarify this relationship in childhood and adolescence and findings may support more targeted and effective health promotion interventions. SIGNIFICANCE: This systematic review shows that motor performance (flexibility, muscle endurance, muscle strength, aerobic capacity, balance and speed) was not associated with BP in children and adolescents. Most of the results were inconsistent because of the lack of studies, risk of bias and low quality of evidence. Only trunk extensor muscle endurance was associated with decreased BP with moderate quality of supporting evidence.

Microscopy-based cellular contractility assay for adult, neonatal, and hiPSC cardiomyocytes.

This protocol provides instructions to acquire high-quality cellular contractility data from adult, neonatal, and human induced pluripotent stem cell-derived cardiomyocytes. Contractility parameters are key to unravel mechanisms underlying cardiac pathologies, yet difficulties in acquiring data can compromise measurement accuracy and reproducibility. We provide optimized steps for microscope and camera setup, as well as cellular selection criteria for different cardiomyocyte cell types, aiming to obtain robust and reliable data. Moreover, we use CONTRACTIONWAVE software to analyze and show the optimized results. For complete details on the use and execution of this profile, please refer to Scalzo et al. (2021).

Antitumor effects of oleandrin in different types of cancers: Systematic review.

Oleandrin, a cardiac glycoside isolated from the leaves of Nerium oleander, has known effects on the heart. Evidence from recent studies have highlighted its potential for anticancer properties. Therefore, we aimed to investigate the effects of oleandrin on cancer cell proliferation, viability and apoptosis in vitro and in vivo. We performed a systematic search in six electronic databases up to Jan 2022. We extracted information about the effects of oleandrin on cell proliferation, cell viability, apoptosis and/or cell cycle arrest in in vitro studies, and the effects on tumor size and volume in animal experimental models. We have retrieved 775 scientific studies. 14 studies met the inclusion criteria. They investigated the effects of oleandrin on breast, lung, pancreatic, colon, prostate, colorectal, oral, ovarian, glioma, melanoma, glioblastoma, osteosarcoma, and histiocytic lymphoma cancers. Overall, in vitro studies demonstrated that oleandrin was able to inhibit cell proliferation, decrease cell viability, and induce apoptosis and/or cell cycle arrest. In addition, oleandrin had an effect on reducing mean tumor size and volume in animal studies. Oleandrin, as a cytotoxic agent, demonstrated antitumor effects in different types of cancers, however important clinical limitations remain a concern. These results encourage future studies to verify the applicability of oleandrin in antineoplastic therapeutic protocols human and veterinary medicine, the investigation of antimetastatic properties, as well as the potential increase in patient survival and the decrease of tumor markers.

Sedentary behavior, physical inactivity, abdominal obesity and obesity in adults and older adults: A systematic review and meta-analysis.

BACKGROUND: Sedentary behavior and physical inactivity may increase the risk of obesity. This systematic review and meta-analysis aimed to investigate: i) the prevalence/incidence of sedentary behavior and physical inactivity, ii) the association of sedentary behavior and physical inactivity with obesity, and iii) the objective and subjective measures, diagnostic criteria, and cut-off points to estimate sedentary behavior and physical inactivity in adults and older adults with obesity. METHODS: We conducted a systematic review and meta-analysis in PubMed, Scielo, Lilacs, and Cochrane Library databases. A meta-analysis of a random-effects model was performed to estimate the combined prevalence of sedentary behavior and physical inactivity and their association with obesity. RESULTS: Twenty-three studies involving 638,000 adults and older adults were included in the systematic review. A meta-analysis was conducted with 111,851 individuals with obesity. The combined prevalence of sedentary behavior was 31% (95% CI, 23-41%), and physical inactivity was 43% (95% CI, 31-55%). Significant associations between obesity and sedentary behavior (OR 1.45, 95% CI, 1.21-1.75) and physical inactivity (OR 1.52, 95% CI, 1.23-1.87) were found. Nine studies have used objective measures to assess physical activity levels, such as accelerometers and pedometers, whereas fourteen applied subjective methods and self-reported questionnaires. CONCLUSIONS: As expected, we found elevated rates of sedentary behavior and physical inactivity in individuals with obesity and a positive risk association. The wide range of objective and subjective measures, methods and cut-offs resulted in great variations of physical inactivity and sedentary behavior estimates. TRIAL REGISTRATION: PROSPERO (CRD42016037747).

Barriers to high school and university students' physical activity: A systematic review.

Physical inactivity commonly occurs throughout one's life, particularly during adolescence and young adulthood. Multiple factors can negatively influence participation in physical activity, but there has been no review examining the barriers to physical activity among high school and university students. Therefore, the aim of this systematic review was to summarize evidence of barriers to the practice of physical activity among high school and university students. The literature search was conducted without time limits using five databases, including CINAHL, Cochrane Library, Embase, PubMed, and Scopus. In total, 59 studies (37 with high school students [n = 22,908] and 22 with university students [n = 15,411]) were included. The main barriers identified in high school and university students were lack of time, lack of motivation, and lack of accessible places. These findings may be useful in designing and implementing evidence-informed interventions and programs for physical activity promotion in students.