Application progress of mesenchymal stem cells in islet transplantation for type 1 diabetes mellitus / 器官移植

Islet transplantation is considered as one of the most effective approach for type 1 diabetes mellitus, although its efficacy is limited by several factors. Anoxia, stress and rejection occurring during the isolation, culturing and transplantation of islets may have impact on the outcome of the islet transplantation. Due to the biological properties such as anti-inflammation, angiogenetic promotion and immune regulation, mesenchymal stem cells (MSCs) are all the way focused by researchers. Additionally, exosome, a derivative of MSC, also plays an import role in regulating anoxia-induced oxidative stress modulation, angiogenetic promotion, and immune regulation. MSC-based islet transplantation may be a useful therapeutic tool in treating type 1 diabetes. Therefore, in this review, the potential effect of MSC prior and posterior to the operation of the islet transplantation, its clinical application as well as its limitations were reviewed, aiming to offer insights into the future application of islet transplantation in treating type 1 diabetes.

Validity of the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) in individuals with Chronic Obstructive Pulmonary Disease in Brazil / Validación de la Escala de Fatiga, Functional Assessment Of Chronic Illness Therapy Fatigue Scale (FACIT-F) en individuos con enfermedad pulmonar obstructiva crónica en Brasil / Validade da Escala de Fadiga, Functional Assessment Of Chronic Illness Therapy Fatigue Scale (FACIT-F) em indivíduos com Doença Pulmonar Obstrutiva Crônica no Brasil

ABSTRACT Fatigue is one of the most prevalent symptoms in individuals with Chronic Obstructive Pulmonary Disease (COPD), but it is poorly evaluated. The Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) is one of the main instruments used to measure fatigue. However, this instrument has not yet been validated for the Brazilian population with COPD. This study aimed to investigate the validity of the FACIT-F fatigue scale in individuals with COPD. In a cross-sectional study, the impact of symptoms (COPD Assessment Test - CAT), dyspnea (modified Medical Research Council - MRC scale), functional capacity (six-minute step test - 6MST), exertional fatigue (Borg modified scale at the end of 6MST), and the FACIT-F scale to assess multidimensional fatigue were evaluated. Concurrent validity was assessed by associating the FACIT-F with the CAT, and convergent validity by associating it with the number of steps, perceived exertional fatigue, and dyspnea. Discriminant validity was assessed by comparing fatigue with the dyspnea severity strata. In total, 92 participants were studied (69.9±8.8 years, FEV1: 48.4% of predicted). The FACIT-F presented an average of 30.1±10.9 points, strong concurrent validity with the CAT (r=-0.80), strong convergent validity with dyspnea (r=−0.66), and low with exercise capacity (r=0.40) and fatigue on exertion (r=-0.44). FACIT-F was effective in discriminating groups with different intensities of dyspnea. Conclusion: The FACIT-F is a valid tool for assessing fatigue in the Brazilian population with COPD.

RESUMEN La fatiga es uno de los síntomas más frecuentes en los individuos con enfermedad pulmonar obstructiva crónica (EPOC), pero su evaluación sigue siendo deficiente. Uno de los principales instrumentos utilizados para medir la fatiga es la Functional assessment of chronic illness therapy fatigue scale (FACIT-F). Sin embargo, este instrumento aún no ha sido validado para la población con EPOC en Brasil. En este contexto, el objetivo de este estudio fue investigar la validez de la escala de fatiga FACIT-F en individuos con EPOC. El estudio transversal evaluó el impacto de los síntomas (COPD Assessment Test -CAT), de la disnea (escala modificada del Consejo de Investigación Médica -MRC), de la capacidad funcional (prueba de pasos de seis minutos -6MST), de la fatiga de esfuerzo (escala modificada de Borg al final de la 6MST) y de la escala FACIT-F para evaluar la fatiga multidimensional. La validez concurrente se evaluó asociando la escala con el CAT, y la validez convergente la asoció con el número de pasos, la fatiga al esfuerzo percibida y la disnea. La validez discriminante se evaluó comparando la fatiga con los estratos de gravedad de la disnea. Se estudió a 92 participantes (69,9±8,8 años, VEF1: 48,4% del predicho). La FACIT-F tuvo una puntuación media de 30,1±10,9, fuerte validez concurrente con el CAT (r=-0,80), fuerte validez convergente con la disnea (r=-0,66) y baja con la capacidad de ejercicio (r=0,40) y con la fatiga de esfuerzo (r=-0,44). La FACIT-F fue eficaz para distinguir grupos con diferentes intensidades de disnea, por lo que muestra ser un instrumento válido para evaluar la fatiga en la población brasileña con EPOC.

RESUMO A fadiga é um dos sintomas mais prevalentes nos indivíduos com Doença Pulmonar Obstrutiva Crônica (DPOC), porém, ainda é pouco avaliada. Um dos principais instrumentos utilizados para mensurar a fadiga é a functional assessment of chronic illness therapy fatigue scale (Facit-F). Entretanto, este instrumento ainda não foi validado para a população com DPOC no Brasil. Dessa forma, o objetivo deste estudo foi investigar a validade da escala de fadiga Facit-F em indivíduos com DPOC. Em um estudo transversal, foram avaliados o impacto dos sintomas (COPD Assessment Test - CAT), a dispneia (escala do Medical Research Council - MRC modificada), a capacidade funcional (teste do degrau de seis Minutos - TD6), a fadiga no esforço (escala de Borg modificada ao final do TD6) e a escala Facit-F para avaliar a fadiga multidimensional. A validade concorrente foi avaliada pela associação da escala com o CAT, e a validade convergente pela associação desta com o número de degraus, percepção de fadiga no esforço e a dispneia. A validade discriminante foi avaliada comparando a fadiga com os estratos da gravidade da dispneia. Foram estudados 92 participantes (69,9±8,8 anos, VEF1: 48,4% do previsto). A Facit-F apresentou uma média de 30,1±10,9 pontos, validade concorrente forte com o CAT (r=-0,80), validade convergente forte com a dispneia (r=-0,66) e baixa com a capacidade de exercício (r=0,40) e com a fadiga ao esforço (r=-0,44). A Facit-F foi eficaz em discriminar grupos com diferentes intensidades de dispneia, portanto é um instrumento válido para a avaliação da fadiga na população brasileira com DPOC.

Recuperación de la frecuencia cardíaca en pacientes con enfermedad pulmonar intersticial difusa

Introducción: La enfermedad pulmonar intersticial difusa no soporta el ejercicio, debido a la sensación de disnea y fatiga durante el esfuerzo de baja intensidad. La recuperación de la frecuencia cardíaca se relaciona con el desempeño en el test de caminata de los seis minutos. Objetivo: Determinar las diferencias sociodemográficas de la función y la capacidad pulmonar en pacientes con enfermedad intersticial difusa, a partir de la recuperación de la frecuencia cardíaca durante el test de caminata de los seis minutos. Métodos: Se realizó un estudio descriptivo de corte transversal. Se calculó la recuperación de la frecuencia cardíaca a partir de la diferencia entre el final del test y los cinco minutos de la prueba. Se conformaron dos grupos de comparación, anormal versus normal, en variables sociodemográficas de la función pulmonar y la capacidad funcional. Resultados: Se vincularon 38 pacientes en el grupo normal y en el anormal 26. En el primero predominaron la edad de 62,26 ± 15,82 y los hombres (52,6 %); mientras que en el grupo anormal los años promediaron entre 58,77 ± 13,23 y sobresalieron las mujeres (61,5 %). Se presentó un valor p < 0,05 del grupo recuperación de la frecuencia anormal en la distancia recorrida, disnea y fatiga al final, un minuto y a los cinco minutos de culminar el test. Conclusiones: Los pacientes con enfermedad pulmonar intersticial difusa con una recuperación de la frecuencia cardíaca anormal presentaron peores resultados en la distancia recorrida, volumen de oxígeno, los equivalentes metabólicos, disnea y fatiga de los miembros inferiores.

Introduction: Diffuse interstitial lung disease does not tolerate exercise, due to the sensation of dyspnea and fatigue during low-intensity exertion. Heart rate recovery is related to performance in the six-minute walk test. Objective: To determine sociodemographic differences in lung function and capacity in patients with diffuse interstitial lung disease, based on heart rate recovery during the 6-minute walk test. Methods: A descriptive cross-sectional study was performed. Heart rate recovery was calculated from the difference between the end of the test and the five minutes of the test. Two comparison groups were formed, abnormal versus normal, in sociodemographic variables of pulmonary function and functional capacity. Results: 38 patients were included in the normal group and 26 in the abnormal group. In the normal group, age was 62.26 ± 15.82 and men were predominant (52.6 %); while in the abnormal group, age averaged 58.77 ± 13.23 and women were predominant (61.5 %). A p-value < 0.05 of the abnormal frequency recovery group was presented in the distance run, dyspnea at the end, fatigue at the end, 1 minute and at 5 minutes after the culmination of the test. Conclusions: Patients with diffuse interstitial lung disease with abnormal heart rate recovery had worse results in distance run, oxygen volume, metabolic equivalents, dyspnea and lower limb fatigue.

Murciélagos como vectores de enfermedades virales e impacto en la salud humana

Introducción: Los murciélagos se destacan por ser los únicos mamíferos voladores, con alrededor de 1 400 especies que cumplen un rol fundamental como controladores de plagas y polinizadores de plantas nocturnas. Sin embargo, su influencia sobre la salud humana se ha evidenciado cada vez más, en particular después del surgimiento de brotes epidémicos de enfermedades virales asociadas a estos mamíferos. Objetivo: Analizar la influencia de los murciélagos en la salud humana, centrándose en su papel como portadores de enfermedades virales y su potencial como reservorios y vectores de enfermedades. Métodos: Se realizó una revisión bibliográfica de la literatura utilizando descriptores MeSH y términos como: Animals, Wild Chiroptera, Virus Diseases, Zoonoses, Disease Vectors, Disease Reservoirs, Public Health, bats, Communicable Disease Control, Disease Outbreaks, Prevention and Control. Se revisaron 1 442 artículos en bases de datos y documentos oficiales, se seleccionaron las fuentes relevantes con Mendeley Desktop 1.19.4. y se obtuvieron al final 47 artículos. Resultados: Existen varias especies de murciélagos que pueden afectar la salud del ser humano y que albergan en especial virus de las familias Filoviridae, Coronaviridae y Paramixoviridae. Los murciélagos se consideran incubadoras óptimas para la propagación de virus debido a su sistema inmune único que lo hace resistente a estos agentes infecciosos. Conclusiones: La vigilancia y monitoreo de los murciélagos, junto con acciones de educación pública y una gestión adecuada de sus hábitats, son fundamentales para la detección temprana y prevención de la transmisión de nuevos virus de estos mamíferos a los humanos.

Introduction: Bats are the only flight mammals, with around 1,400 species playing critical roles as pest controllers and nocturnal plant pollinators. However, its impact on human health has become increasingly evident, especially after the appearance of epidemic outbreaks of viral diseases related to these mammals. Objetive: To analyze the influence of bats on human health, focusing on their role as carriers of viral diseases and their potential as reservoirs and vectors of diseases. Methods: A literature bibliographical review was conducted using MeSH descriptors and keywords such as: Animals, Wild Chiroptera, Virus Diseases, Zoonosis, Disease Vectors, Disease Reservoirs, Public Health, bats, Communicable Disease Control, Disease Outbreaks, Prevention and Control. 1442 articles in databases and official documents were reviewed, selecting the relevant sources with Mendeley Desktop 1.19.4., obtaining 47 articles at the end. Results: There are several species of bats that can affect human health and that mainly harbor viruses from the Filoviridae families, Coronaviridae and Paramyxoviridae. Bats are considered optimal incubators for the spread of the virus due to their unique immune system that makes them particularly resistant to these infectious agents. Conclusions: Surveillance and monitoring of bats, together with public education actions and proper management of their habitats, are essential for early detection and prevention of transmission of new viruses from these mammals to humans.

Avaliação da concordância entre os resultados da genotipagem do polimorfismo C/T-13910 e do teste de tolerância à lactose: um estudo retrospectivo populacional no Brasil / Evaluation of agreement between c/t-13910 polymorphism genotyping results and lactose tolerance test results: a retrospective population-based study in brazil

ABSTRACT Background: Lactose tolerant test (LTT) is the most broadly used diagnostic test for lactose intolerance in Brazil, is an indirect, minimally invasive and a low-cost test that is widely available in primary care and useful in clinical practice. The C/T-13910 polymorphism in lactase persistence has been well characterized in Caucasian populations, but there are no studies evaluating the concordance between C/T-13910 polymorphism genotyping results and LTT results in Brazil, where the population is highly mixed. Objective: We aimed to evaluate agreement between presence of C/T-13910 polymorphism genotyping and malabsorption in LTT results. Methods: This is a retrospective analysis of a Brazilian population whose data were collected from a single laboratory database present in several Brazilian states. Results of individuals who underwent both genetic testing for lactose intolerance (C/T-13910 polymorphism genotyping) and an LTT from April 2016 until February 2019 were analysed to evaluate agreement between tests. Groups were classified according to age (<10-year-old (yo), 10-17 yo, ≥18 yo groups) and state of residence (São Paulo or Rio Grande do Sul). Results: Among the 404 patients evaluated, there was agreement between the genotyping and LTT results in 325 (80.4%) patients and discordance in 79 (19.6%) patients (k=0.42 -moderate agreement). Regarding the genotype, 47 patients with genotype C/C (lactase nonpersistence) had normal LTT results, and 32 with genotype C/T or T/T (indicating lactase persistence) had abnormal LTT results. Neither age nor state of residence (Rio Grande do Sul or São Paulo) affected the agreement between test results. Conclusion: Considering the moderate agreement between C/T-13910 polymorphism genotyping and LTT results (κ=0.42) in the Brazilian population, we hypothesize that an analysis of other polymorphisms could be a strategy to improve the agreement between genotyping and established tests and suggest that additional studies should focus on exploring this approach.

RESUMO Contexto: O teste de tolerancia à lactose (TTL) é ampliamente utilizado por ser minimamente invasivo e de baixo custo, disponível na atenção primária e muito útil na prática clínica. Está bem estabelecido o polimorfismo C/T-13910 na persistência da lactase em populações caucasianas, mas não há estudos avaliando a concordância entre os resultados da genotipagem do polimorfismo C/T-13910 e do TTL no Brasil, onde a população é altamente miscigenada. Objetivo: Avaliar a concordância entre a presença do polimorfismo C/T-13910 e a má absorção nos resultados do TTL. Métodos: Análise retrospectiva de dados coletados de um laboratorio presente em vários estados brasileiros. Os resultados dos pacientes que realizaram um teste genético para intolerância à lactose (genotipagem do polimorfismo C/T-13910) e um TTL de abril de 2016 a fevereiro de 2019 foram analisados para avaliar a concordância entre os testes. Os grupos foram classificados de acordo com a idade (<10 anos; 10-17 anos, ≥18 anos) e estado de residência (São Paulo ou Rio Grande do Sul). Resultados: Entre os 404 pacientes avaliados, houve concordância entre os resultados de genotipagem e TTL em 325 (80,4%) pacientes e discordância em 79 (19,6%) pacientes (K=0,42 - concordância moderada). Em relação ao genótipo, 47 pacientes com genótipo C/C (não persistência de lactase) apresentaram TTL normal e 32 com genótipo C/T ou T/T (indicando persistência da lactase) apresentaram TTL anormal. A idade e o estado de residência (Rio Grande do Sul ou São Paulo) não afetaram a concordância entre os resultados dos exames. Conclusão: Considerando a concordância moderada entre a genotipagem do polimorfismo C/T-13910 e os resultados de TTL (κ=0,42) na população brasileira, sugerimos que a análise de outros polimorfismos poderia ser uma estratégia para melhorar a concordância entre os testes.

Enfermedades asociadas e indicadores metabólicos en personas con esquizofrenia / Associated Diseases and Metabolic Indicators in Schizophrenic Individuals

La esquizofrenia es una enfermedad que está caracterizada por su complejidad psicopatológica agravada por una frecuente asociación de enfermedades físicas como la obesidad, la intolerancia a la glucosa, la diabetes y la dislipidemia. Además, indicadores metabólicos como la glucemia, el colesterol y los triglicéridos en sangre, así como la obesidad, tienen relevancia en estos pacientes, según lo planteado en la literatura especializada sobre el tema. Por otra parte, las enfermedades físicas asociadas como los indicadores metabólicos, tienen su impacto en el sistema nervioso central con independencia de la esquizofrenia. La suma de los trastornos mentales y físicos implica la necesidad de atender ambos problemas simultáneamente y se recomienda la intervención interdisciplinaria. El protocolo de actuación para la atención de los pacientes con esquizofrenia y psicosis relacionadas en el Hospital Clínico Quirúrgico Hermanos Ameijeiras es un ejemplo del abordaje señalado(AU)

Schizophrenia is a disease characterized by a psychopathological complexity, aggravated by frequent association of physical diseases such as obesity, glucose intolerance, diabetes and dyslipidemia. In addition, there are other metabolic indicators such as blood glucose, cholesterol and triglycerides which are relevant in these patients, and the international literature has been suggested so. On the other hand, both associated physical diseases and metabolic indicators have their impact on the central nervous system in addition to schizophrenia. The sum of mental and physical disorders implies the need to address both problems simultaneously, which is why interdisciplinary intervention is recommended. Hermanos Ameijeiras Clinical Surgical Hospital is an example of the action protocol for patients with schizophrenia and psychosis(AU)

Avaliação Cardiodinâmica Não Invasiva por Cardiografia de Impedância durante o Teste de Caminhada de Seis Minutos em Pacientes com Insuficiência Cardíaca / Non-Invasive Assessment of Cardiodynamics by Impedance Cardiography during the Six-Minute Walk Test in Patients with Heart Failure

Resumo Fundamento O Teste de Caminhada de seis Minutos (TC6M) é comumente usado para avaliar pacientes com insuficiência cardíaca. No entanto, vários fatores clínicos podem influenciar a distância percorrida pelos pacientes no teste. A cardiografia de impedância (CI) na avaliação morfológica é uma ferramenta útil para avaliar a hemodinâmica cardíaca de maneira não invasiva. Objetivo Este estudo teve como objetivo comparar as respostas de aceleração e desaceleração do Débito Cardíaco (DC), da Frequência Cardíaca (FC), e do Volume Sistólico (VS) ao TC6M de indivíduos com insuficiência cardíaca e fração de ejeção reduzida (ICFEr) com as de controles sadios. Métodos Este é um estudo transversal observacional. O DC, a FC, o VS e o Índice Cardíaco (IC) foram avaliados antes, durante e após o TC6M por CI. O nível de significância adotado na análise estatística foi 5%. Resultados Foram incluídos 27 participantes (13 com ICFEr e 14 controles sadios). A aceleração do DC e da FC foi significativamente diferente entre os grupos (p<0,01 e p=0,039, respectivamente). Encontramos diferenças significativas no VS, no DC e no IC entre os grupos (p<0,01). A regressão linear mostrou uma contribuição deficiente do VS à mudança no DC no grupo com ICFEr (22,9% versus 57,4%). Conclusão O principal resultado deste estudo foi o fato de que indivíduos com ICFEr apresentaram valores mais baixos de aceleração do DC e da FC durante o teste de exercício submáximo em comparação a controles sadios. Isso pode indicar um desequilíbrio na resposta autonômica ao exercício nessa condição.

Abstract Background The six-minute walk test (6MWT) is commonly used to evaluate heart failure (HF) patients. However, several clinical factors can influence the distance walked in the test. Signal-morphology impedance cardiography (SM-ICG) is a useful tool to noninvasively assess hemodynamics. Objective This study aimed to compare cardiac output (CO), heart rate (HR), and stroke volume (SV) acceleration and deceleration responses to 6MWT in individuals with HF and reduced ejection fraction (HFrEF) and healthy controls. Methods This is a cross-sectional observational study. CO, HR, SV and cardiac index (CI) were evaluated before, during, and after the 6MWT assessed by SM-ICG. The level of significance adopted in the statistical analysis was 5%. Results Twenty-seven participants were included (13 HFrEF and 14 healthy controls). CO and HR acceleration significantly differed between groups (p<0.01; p=0.039, respectively). We found significant differences in SV, CO and CI between groups (p<0.01). Linear regression showed an impaired SV contribution to CO change in HFrEF group (22.9% versus 57.4%). Conclusion The main finding of the study was that individuals with HFrEF showed lower CO and HR acceleration values during the submaximal exercise test compared to healthy controls. This may indicate an imbalance in the autonomic response to exercise in this condition.

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

ABSTRACT Introduction: Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD. Objective and Method: Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD. Results: Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls. Conclusion: Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.

COVID-19 en las embarazadas. Riesgo de las complicaciones durante el embarazo y en el neonato / COVID-19 in pregnant women. Risk of complications during pregnancy and in the newborn

Sobre el tema COVID-19 se han publicado múltiples estudios que reflejan su elevada incidencia, transmisibilidad, morbilidad y mortalidad, con gran repercusión y severidad en los grupos poblacionales de riesgo. El embarazo no escapa a ello, y la inmunosupresión fisiológica que se presenta en esta condición, hace a la gestante y al neonato, ser más susceptibles a las enfermedades infecciosas. El objetivo de esta comunicación es profundizar en la fisiopatología y la repercusión de la enfermedad COVID-19 en las gestantes y el neonato, para mejorar el conocimiento relacionado con el tema, el cual repercutirá en un mejor manejo de estos pacientes. Para ello, se realizó una revisión de investigaciones publicadas en el período comprendido entre enero y diciembre de 2021, en las bases de datos: SciELO, SCOPUS, Medline, Dialnet, Cumed y Lilacs. De los 44 artículos obtenidos inicialmente, 33 cumplieron los criterios de inclusión.

Several studies on COVID-19 have been published reflecting its high incidence, transmissibility, morbidity and mortality, with great repercussions and severity in population groups at risk. Pregnancy does not escape from this, and the physiological immunosuppression that occurs in this condition makes the pregnant woman and the newborn more susceptible to infectious diseases. The objective of this communication is to deepen the pathophysiology and the repercussion of the COVID-19 disease in pregnant women and the newborn in order to improve knowledge related to the subject, which will have an impact on better management of these patients. For this, a review of research published between January and December 2021 was carried out in the databases such as SciELO, SCOPUS, Medline, Dialnet, Cumed and Lilacs. A number of 33 articles met the inclusion criteria from 44 initially obtained.

Fatores correlacionados a intolerância ao exercício na alta de pacientes hospitalizados por COVID-19 / Factors correlated to exercise intolerance upon discharge in patients hospitalized for COVID-19

Objetivo: Verificar a prevalência da intolerância ao exercício e a correlação com o perfil sociodemográfico, clínico, de hospitalização e função física na alta de pacientes hospitalizados pela COVID-19. Métodos: Estudo transversal com 52 pacientes internados por COVID-19 no Hospital Santa Casa de Misericórdia de Vitória, Espírito Santo. Coletou-se informações no momento da alta quanto ao perfil sociodemográfico, clínico, de hospitalização e função física, através de questionário semiestruturado, prontuário eletrônico, escalas e testes. Utilizou-se o Medical Research Council Modificado (mMRC) para graduar a dispneia, o Medical Research Council (MRC) para avaliar força muscular periférica, a manovacuometria, através das pressões inspiratória e expiratória máximas, para mensurar força muscular respiratória e a Medida de Independência Funcional (MIF) para funcionalidade. A variável desfecho, tolerância ao exercício, foi medida pelo Teste de Sentar e Levantar de 1 minuto. Resultados: Todos participantes apresentaram intolerância ao exercício no momento da alta hospitalar. O desempenho no teste de sentar e levantar foi inversamente correlacionado com o grau de dispneia e diretamente com a força muscular inspiratória, pontuação total da Medida de Independência Funcional, domínios de autocuidado, locomoção, mobilidade (p 0,019), e controle de esfíncter Conclusão: A prevalência da intolerância ao exercício na alta por COVID-19 foi de 100%, e estava correlacionada com o grau de dispneia, força muscular inspiratória e funcionalidade para autocuidado, locomoção, mobilidade e controle de esfíncter. Destaca-se a avaliação da tolerância ao exercício como importante preditor de sequelas pós-COVID-19, capaz de avaliar a interação entre diversos sistemas orgânicos.

Objective: To verify the prevalence of exercise intolerance and the correlation with the sociodemographic, clinical, hospitalization and physical function profile at discharge of patients hospitalized for COVID-19. Methods: Cross-sectional study with 52 patients hospitalized for COVID-19 at Hospital Santa Casa de Misericórdia in Vitória, Espírito Santo. Information was collected at discharge regarding the sociodemographic, clinical, hospitalization and physical function profile, through a semi-structured questionnaire, electronic medical record, scales and tests. The Modified Medical Research Council (mMRC) was used to grade dyspnea, the Medical Research Council (MRC) was used to assess peripheral muscle strength, manovacuometry, through maximal inspiratory and expiratory pressures, to measure respiratory muscle strength and the Independence Measure Functional (MIF) for functionality. The outcome variable, exercise tolerance, was measured by the 1-minute Sit and Stand Test. Results: All participants presented exercise intolerance at discharge. Performance in the 1-minute Sit and Stand Test was inversely correlated with the degree of dyspnea and directly with inspiratory muscle strength, total score on the Independence Measure Functional, self-care domains, locomotion, mobility and sphincter control. Conclusion: The prevalence of exercise intolerance at discharge due to COVID-19 was 100%, and was correlated with the degree of dyspnea, inspiratory muscle strength and functionality for self-care, locomotion, mobility and sphincter control. The assessment of exercise tolerance stands out as an important predictor of sequelae after COVID-19, capable of assessing the interaction between different

USPSTF and ISPAD Guidelines on Screening for Prediabetes and Type 2 Diabetes in Children and Adolescents

The rising trends of obesity, metabolic syndrome and diabetes in adults are worrisome globally. The majority of antecedents to adult noncommunicable diseases begin in childhood. Type 2 diabetes is recognized as one of the major diseases that contribute to the NCD burden in childhood. Recently, the US Preventive Services Task Force (USPSTF) and the International Society for Pediatric and Adolescent Diabetes (ISPAD) released their guidelines on diagnosis and management of prediabetes and diabetes in children targeted screening for youth-onset type 2 diabetes is suggested in at-risk children (obese, positive family history of type 2 diabetes, etc.), while the role of screening asymptomatic children is not substantiated. Obesity and insulin resistance are important risk factors for type 2 diabetes. The cutoffs of fasting plasma glucose for the diagnosis of prediabetes and diabetes are >100 to 125 and ?126 mg/dL, respectively. This update briefly summarizes the recommendations on screening for youth-onset prediabetes and type 2 diabetes.

La prueba cardiopulmonar de ejercicio contribuye a determinar con precisión el riesgo en pacientes con hipertensión pulmonar de bajo riesgo / Cardiopulmonary Exercise Testing Contributes to Accurate Risk Assessment in Patients with Low-risk Pulmonary Hypertension

RESUMEN Introducción : Las guías europeas de hipertensión arterial pulmonar (HAP) estratifican el riesgo valiéndose de características clínicas y estudios complementarios entre los cuales está la prueba cardiopulmonar de ejercicio (PCPE), de la cual toma en cuenta 3 parámetros: el consumo de O2 (VO2) pico, su porcentaje respecto del predicho y la pendiente ventilación minuto/ producción de dióxido de carbono (VE/VCO2). Sin embargo, ninguno de los modelos que validaron esta forma de estratificar el riesgo incluyeron la PCPE entre sus variables. Objetivos : Determinar qué proporción de pacientes con HAP del grupo I considerados de bajo riesgo y que caminan >440 metros en la prueba de caminata de 6 minutos (PC6M) tienen en la PCPE parámetros considerados de riesgo moderado o alto. Material y métodos : Se incluyeron pacientes >18 años con diagnóstico de HAP del grupo I considerados de bajo riesgo con una PC6M >400 metros a los que se les realizó una PCPE en la que se registró el VO2 pico, su porcentaje respecto del VO2 predicho y la pendiente VE/VCO2. Se determinó qué proporción de pacientes presentaban estos parámetros en un estrato de riesgo mayor a bajo riesgo (VO2 pico <15 ml/kg/min, su porcentaje respecto del predicho <65% y la pendiente VE/VCO2 >36). Resultados : Se incluyeron 18 pacientes. A pesar de ser pacientes de bajo riesgo y con buena clase funcional todos presentaron un VO2 pico menor al 85% del predicho, lo cual determina un deterioro al menos leve de la capacidad funcional. Un único paciente (6%) presentó los tres parámetros evaluados en bajo riesgo, 8 pacientes (44%) tuvieron al menos un parámetro alterado, 7 pacientes (39%) presentaron 2 parámetros alterados y en 2 pacientes (11%) todos los parámetros estuvieron alterados. Los parámetros que más frecuentemente se vieron alterados fueron el porcentaje respecto del VO2 predicho y la pendiente VE/VCO2, en el 67% de los casos. Solo 4 pacientes presentaron un VO2 pico <15 ml/k/m. Ningún paciente presentó valores de VO2 pico o porcentaje respecto del predicho en la categoría de alto riesgo. Sin embargo, 6 pacientes (33%) presentaron una pendiente VE/VCO2 considerada de alto riesgo. Conclusión : El 94% de los pacientes considerados de bajo riesgo presentaron al menos una variable en la PCPE que no corresponde a un perfil de riesgo bajo. La pendiente VE/VCO2 y el porcentaje de VO2 pico respecto del predicho fueron las variables más frecuentemente alteradas. La pendiente VE/VCO2 fue la única que mostró valores considerados de alto riesgo. La PCPE podría tener un lugar en la estratificación de precisión de pacientes de bajo riesgo. El valor de este hallazgo deberá ser evaluado en estudios prospectivos, al tiempo que genera las bases para el planteo de hipótesis respecto de la estratificación de riesgo y la intensidad del tratamiento en pacientes que aparentan estar en bajo riesgo.

ABSTRACT Background : European guidelines for pulmonary arterial hypertension (PAH) stratify the risk using clinical characteristics and complementary studies, including the cardiopulmonary exercise test (CPET). This takes into account 3 parameters: peak O2 consumption (peak VO2), its percentage with respect to the predicted VO2, and the minute ventilation/carbon dioxide production (VE/VCO2) slope. However, none of the models that validated this way of stratifying risk included PCPE among their variables. Objectives : To determine what proportion of patients with group I PAH considered to be at low risk and who walk >440 meters in the 6-minute walk test (6MWT) have parameters considered to be of moderate or high risk in the PCPE. Methods : Patients >18 years of age, diagnosed with group I PAH at low risk of events, who walked >440 meters in the 6MWT and had NT-proBNP value <300 pg/dL were included. A CPET was performed in which the peak VO2, its percentage with respect to the predicted VO2, and the VE/VCO2 slope were recorded. It was determined what proportion of patients presented these parameters in a higher than low risk stratum (peak VO2 consumption ≤15 ml/min/Kg, its percentage with respect to the predicted VO2 ≤65% and the VE/VCO2 slope ≥36). Results : Eighteen patients were included. Despite being low-risk patients with a good functional class, all patients presented a peak VO2 less than 85% of predicted, which determines a deterioration of functional capacity. A single patient (6%) presented the three parameters evaluated at low risk, 8 patients (44%) had at least one altered parameter, 7 patients (39%) presented 2 altered parameters and in 2 patients (11%) all parameters were altered. The parameters that were most frequently altered were the percentage of predicted peak VO2 and the VE/VCO2 slope in 67% of the cases. Only 4 patients presented a peak VO2 <15 ml/kg/m. No patient presented peak VO2 values or percentage of predicted VO2 in the high-risk category. However, 6 patients (33%) presented a high-risk VE/VCO2 slope. Conclusion : Majority (92%) of the patients considered low risk and who walk more than 440 meters in 6 minutes presented at least one altered variable in the CPET. The VE/VCO2 slope and the percentage of predicted peak VO2 consumption were the most frequently altered variables. The VE/VCO2 slope was the only one that showed values considered high risk. CPET could have a place in the precision stratification of low-risk patients. The value of this finding should be evaluated in prospective studies.

Prevalence of Undiagnosed Diabetes and Impaired Glucose Tolerance in a Semi-urban Population from Calicut City

Though the prevalence of Diabetes is increasing worldwide, a thorough knowledge of the prevalence of undiagnosed Diabetes a pre-diabetes is lacking. This study from India is to evaluate the prevalence of asymptomatic diabetes among adults with comorbidities and without any history of Diabetes. Prevalence of asymptomatic individuals with Diabetes and impaired glucose tolerancewas 3% and 15%, respectively. The high prevalence found in the study raises concern over the health care indices and the need for urgent public health action to control the pandemic. Regular screening for Diabetes in adults is required to prevent complications of long-term diabetes

Research and application progress in adoptive re-transfusion of regulatory cells in organ transplantation / 器官移植

Rejection and adverse reactions caused by long-term use of immunosuppressants severely affect the survival rate and quality of life of organ transplant recipients. Immune tolerance induction plays a key role in improving the survival rate and quality of life of organ transplant recipients. In recent years, tremendous progress has been achieved in adoptive re-transfusion of regulatory cells. In this article, research progress in regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC) and regulatory B cell (Breg) in animal experiment and clinical application was reviewed, and the main clinical problems of adoptive re-transfusion of regulatory cells, the application of chimeric antigen receptor Treg and the concept of cell therapy in immune evaluation were summarized, aiming to deepen the understanding of regulatory cell therapy, promote the application of regulatory cells in immune tolerance of organ transplantation, and improve clinical efficacy of organ transplantation and the quality of life of recipients.

Effect of apatinib combined with fluzoparib on proliferation ability of human ovarian cancer cisplatin-resistant cells / 肿瘤研究与临床

Objective:To investigate the effect of apatinib and fluzoparib on the proliferation ability of cisplatin-resistant human ovarian cancer cells.Methods:Human ovarian cancer cells SKOV3 and cisplatin-resistant SKOV3/DDP cells of human ovarian cancer were treated with different concentrations of 1, 2, 4, 8, 16, 32, 64,128 μg/ml cisplatin at different times; CCK-8 method was used to detect the proliferation rate and half-inhibitory concentration ( IC50) of SKOV3 and SKOV3/DDP cells, and the drug-resistance fold of SKOV3/DDP cell was also calculated. SKOV3/DDP cells were treated with different concentrations of apatinib (4, 8, 16, 32, 64 μmol/L) and fluzoparib (148.15, 222.22, 333.33, 500.00, 750.00 μmol/L) for 24 h, 48 h and 72 h, respectively; the cell proliferation rate was determined by using CCK-8 method and IC50 was calculated. SKOV3/DDP cells were divided into the blank control group (cells untreated with drugs), cisplatin group, cisplatin + apatinib group, cisplatin + fluzoparib group, cisplatin + fluzoparib + apatinib group, and drug intervention was given in each group; the inhibition rate of cells in each group was detected by using CCK8 method. Results:The proliferation rate of SKOV3 cells treated with the same concentration of cisplatin for the same time was lower than that of SKOV3/DDP cells, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 4, 8, 16, 32, 64 μmol/L apatinib was 742.1μmol/L at 24 h, 156.8 μmol/L at 48 h, and 77.5 μmol/L at 72 h. Compared with the control group, the proliferation rate of SKOV3/DDP cells treated with apatinib at an effective concentration greater than 32 μmol/L was significantly decreased, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 148.15, 222.22, 333.33, 500.00, 750.00 μmol/L fluzoparib was 878.5 μmol/L at 24 h, 406.7 μmol/L at 48 h, and 283.3μmol/L at 72 h. When the effective concentration of fluzoparib was more than 333.33 μmol/L for 24 h, the proliferation rate of SKOV3/DDP cells was lower than that of the control group, and the differences were statistically significant (all P < 0.05). Compared with the control group, the proliferation rate of SKOV3/DDP cells was decreased when the effective concentration was more than 148.15 μmol/L at 48 h and 72 h, and the differences were statistically significant (all P < 0.05). The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib group was lower than that of 5 μg/ml cisplatin group [(40.4±1.4)% vs. (62.7±1.4)%, t = 20.22, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(5.2±0.4)% vs. (62.7±1.4)%, t = 52.04, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(0.3±0.8)% vs. (62.7±1.4)%, t = 53.98, P < 0.001]. The 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group had the lowest proliferation rate of SKOV3/DDP cells, which was lower than that of 5μg/ml cisplatin + 64 μmol/L apatinib group and 5 μg/ml cisplatin + 290 μmol/L fluzoparib group (all P < 0.001). Conclusions:Apatinib and fluzoparib can enhance the sensitivity of human ovarian cancer cisplatin-resistant cells SKOV3/DDP to cisplatin, and the combination of drugs can produce the stronger inhibitory effects and reverse cisplatin resistance of ovarian cancer.

Chronic infection of hepatitis B virus and cellular immunity / 中华微生物学和免疫学杂志

The persistent infection of hepatitis B virus (HBV) is the result of lacking specific immunity against the virus. This state is also called immune tolerance to HBV. In most cases, acute HBV infection in adults can induce specific immune response which can clear the virus. Perinatal HBV infection, however, usually progresses to chronic infection, indicating a defect in HBV-specific immune response. A typical specific immune response includes four processes, which were antigen presentation, specific CD4 + T cell activation, specific CD8 + T cell activation and B cell activation. There must be some dysfunctions in some or all of the four processes during chronic HBV infection. This article discussed the relationship between chronic HBV infection and cellular immunity, hoping to provide a reference for further study on the reconstitution of specific immunity against HBV.

Efficacy of different enteral nutrition drugs for severe acute pancreatitis and their gastrointestinal tolerance / 中国药房

OBJECTIVE To compare the efficacy of different enteral nutrition （EN） drugs for severe acute pancreatitis （SAP） and their gastrointestinal tolerance. METHODS A total of 118 SAP patients admitted to the Pancreatic Center of Jiangsu Provincial People’s Hospital from January 1， 2022 to June 30， 2023 were collected and divided into short-peptide EN drugs （SP） group （41 cases）， dietary fiber-free intact protein EN drugs （TP-MCT） group （40 cases） and dietary fiber-containing intact protein EN drugs （TPF-DM） group （37 cases） according to the types of EN. All three groups of patients were given continuous pumps of EN drugs via nasal feeding for 24 hours， with a target energy dose of 25-30 kcal/kg. The blood nutritional indexes [albumin （ALB）， total protein （TP）， hemoglobin （Hb）， globulin （GLB）]， inflammation indexes [white blood cells （WBC）， percentage of neutrophils （N%）， procalcitonin （PCT）， C-reactive protein （CRP）， interleukin-6 （IL-6）]， clinical outcomes indexes [time of stay in the intensive care unit （ICU）， length of hospital stay， duration of resuming oral diet， the rate of cases without improvement， mortality rate] and the occurrence of gastrointestinal tolerance were collected from 3 groups before medication and 7 d after medication. RESULTS After treatment， ALB and TP in 3 groups were significantly higher than before treatment （P＜0.05）； CRP and N% of 3 groups， PCT of TP-MCT group and IL-6 of SP group were significantly lower than corresponding group before medication （P＜ 0.05）； PCT of TP-MCT group and IL-6 of SP group were significantly lower than those of other two groups at corresponding period （P＜0.05）. There were no statistical significances in ALB， TP， CRP or N% among the three groups after medication， and in Hb， GLB or WBC among the three groups before and after treatment （P＞0.05）. There was no significant difference in clinical outcome indexes among 3 groups （P＞0.05）. The incidence of gastrointestinal adverse reactions in the TP-MCT group was the lowest （32.50%）， and significantly lower than those in the SP group （46.34%） and TPF-DM group （48.65%） （P＜0.05）. CONCLUSIONS Different EN preparations can improve the nutritional status and reduce the inflammatory response in SAP patients to different extents， among which SP and TP-MCT are more effective， and TP-MCT shows the better gastrointestinal tolerance.

Study on the mechanism of VEGF inducing tolerogenic dendritic cells in oral squamous cell carcinoma / 口腔医学

Objective@#To investigate the mechanism of vascular endothelial growth factor(VEGF) inducing tolerogenic dendritic cells(DCs) in oral squamous cell carcinoma (OSCC).@*Methods@#The DCs were divided into four groups: Control group (DC), VEGF group (VEGF added into DC), Co-culture group (DC co-cultured with SCC7) and Anti-VEGF group (anti-VEGF antibody added into DC co-cultured with SCC7). Flow cytometry (FCM) was used to detect DC surface markers. To detect the effect of DC on proliferation activity of T lymphocyte, the experiment included five groups: Nc group (T lymphocyte), Control group (T lymphocyte added into DC), VEGF group (T lymphocyte + DC + VEGF), Co-culture group (T lymphocyte + DC + supernatant of SCC7) and Anti-VEGF group (T lymphocyte + DC + supernatant of SCC7 + anti-VEGF antibody). Subsequently, the mixed lymphocyte reaction(MLR) was conducted. The expression levels of indole-2, 3-doxygenase(IDO)and programmed cell death 1 ligand 1(PD-L1)in DC were detected by western blot, real time PCR and FCM respectively. For the cytotoxic lymphocyte (CTL) assay, SCC7 cells and CTLs were mixed and CTL-mediated SCC7 cells cytotoxicity was tested. The experiment included four groups: Control group (T lymphocyte + DC), IDO inhibition group (T lymphocyte + DC + IDO inhibitor), Anti-PD-L1 antibody group (T lymphocyte + DC + anti-PD-L1 antibody) and Combination group (T lymphocyte + DC + IDO inhibitor + anti-PD-L1 antibody). The SCC7 tumor-bearing mice treated with IDO inhibitor and the anti-PD-L1 antibody were sacrificed and the tumor inhibition rate and the spleen index were determined. @*Results@#Compared with Control group, exogenous VEGF or SCC7 co-culture inhibited the relative number of DC expressing CD11C, CD80, CD86, CD40 and MHC Ⅱ. The positive DCs were increased in the Anti-VEGF group compared with VEGF or Co-culture group. In VEGF or Co-culture group, the number of T cells stimulated by SCC7-pulsed DCs was decreased compared with Control group. However, the ability of Anti-VEGF group to induce T cell proliferation was significantly increased compared with VEGF or Co-culture group. Significantly increased expression of IDO and PD-L1 were observed in VEGF and Co-culture group. However, this was partially reversed by addition of anti-VEGF antibody into the co-culture system. Compared with Control group, the expressions of CD11C and CD86 in DC in both the IDO inhibition group and Anti-PD-L1 antibody group were increased, and were significantly higher in the Combination group compared with the single drug groups. The similar results were exhibited in MLR and CTL assay. In vivo, the results revealed that the tumors obtained from the mice in three experimental groups were smaller than those in the control group. Furthermore, the tumor volume of the Combination group was the smallest. The spleen index of each group was calculated and the results showed the spleen index of the three experimental groups was significantly higher than that of Control group.@*Conclusion@#VEGF in OSCC micro-environment inhibits the maturation and function of DC that are transformed into tolerogenic DC by high expression of IDO and PD-L1.

Research progress on radiobiological effects of ferroptosis in cancer / 中华放射肿瘤学杂志

Ferroptosis is a new form of regulated cell death discovered in recent years, which is iron-dependent cell death characterized by peroxidation of polyunsaturated fatty acid phospholipids. Recent studies have shown that radiotherapy can induce ferroptosis in cancer cells via ionizing radiation. Targeting ferroptosis plays a synergistic role in tumor suppression with radiation, which not only further deepens the connotation of radiobiology, but also provides a new perspective for tumor radiosensitization. This review systematically summarizes the occurrence and defense of ferroptosis, focusing on the key role of ferroptosis in the radiobiological effects of tumor cells and the potential application of ferroptosis in radiosensitization.

Study on the inhibitory effect of UBE2T on radiosensitivity of lung adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.