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Graphene and its derivatives have emerged in recent years as promising materials for use in regenerative medicine. It has been reported that graphene can mitigate inflammatory responses in the human body, which enhances the biological behavior of the biomaterial containing it. Moreover, the high chemical stability and large specific surface area of graphene favor the absorption, binding, and delivery of antibodies, drugs, enzymes, and other molecules. This work brings a short review on the use of graphene as a biomaterial, focusing on its processing, structure, properties, and applications. Besides, the potential use of this material in the biomedical field is addressed here, devoting significant attention to the Brazilian potential to develop and produce novel graphene-based composites for regenerative medicine. As discussed here, Brazil has universities and research centers of excellence with expertise and know-how in the preparation of graphitic materials, which is a result of more than two decades of investments. Regenerative medicine is a research field of strategic importance for Brazil, which is a consequence of the accelerated aging experienced by the Brazilian population in the last decades. Despite the efforts directed in recent years toward the development and use of graphene and its derivatives in the biomedical field, important obstacles must be addressed. Here we discuss these issues and initiatives taken in an attempt to overcome them.

Background: Atrial fibrillation (AF) frequently coexists with congestive heart failure (CHF). The increased susceptibility to AF in CHF has been attributed to a variety of structural and electrophysiological changes in the atria, particularly dilation and interstitial fibrosis. We evaluated atrial remodeling and AF vulnerability in a rat model of CHF induced by left ventricle (LV) radiofrequency (RF) ablation. Methods: Wistar rats were divided into 3 groups: RF-induced CHF (Ab, n = 36), CHF animals treated with spironolactone (AbSpi, n = 20) and sham controls (Sham, n = 29). After 12 weeks, animals underwent echocardiographic and electrophysiological evaluation and were sacrificed for histological (atrial fibrosis) and Western blotting (TGF-β1, collagen I/III, connexin 43 and CaV1.2) analysis. Results: Mild LV dysfunction and marked atrial enlargement were noted in both ablated groups. AF inducibility (episodes ≥2 s) increased in the Ab group compared to sham animals (31/36, 86%; vs. 15/29, 52%; p = 0.005), but did not differ from the AbSpi group (16/20, 80%; p = NS). Sustained AF (>30 s) was also more frequent in the Ab group compared to shams (56% vs. 28%; p = 0.04). Spironolactone reduced atrial fibrosis (p

Artrite reumatóide é uma doença difusa do tecido conjuntivo que se caracteriza pelo acometimento articular e sistêmico. Disfunções hematológicas como anemia ocorrem em até 65% dos pacientes, sendo a anemia das doenças crônicas a forma mais comum. A anemia hemolítica auto-imune pode estar associada à difusa do tecido conjuntivo, sendo classicamente associada ao lúpus eritematoso sistêmico e fazendo parte dos seus critérios de classificação. A presença de anemia hemolítica auto-imune em artrite reumatóide é relatada raramente na literatura e os mecanismos etiopatogênicos para o seu desenvolvimento ainda não estão esclarecidos. Descrevemos um caso de artrite reumatóide no adulto e outro de artrite reumatóide juvenil que desenvolveram anemia hemolítica auto-imune e discutimos os prováveis mecanismos etiopatogênicos envolvidos.Rheumatoid arthritis is a connective tissue disease characterized by articular and systemic involvement. Hematological abnormalities such as anemia may occur in up to 65% of the patients, with chronic disease anemia being the commonest form. Autoimmune hemolytic anemia can be associated with different connective tissue diseases, particularly systemic lupus erythematosus and it is part of its classification criteria. On the other hand, the presence of autoimmune hemolytic anemia in rheumatoid arthritis has rarely been described in the literature and the pathogenic mechanisms for its development remain unclear. We describe here a case of rheumatoid arthritis and another of juvenile rheumatoid arthritis that developed to autoimmune hemolytic anemia and present the probable etiopathogenic mechanisms.

Introdução: O vírus da Hepatite E (HEV) é responsável pelo desenvolvimento da hepatite E, e sua principal via de transmissão é fecal-oral. O genótipo 3 (HEV-3), zoonótico, está globalmente distribuído, sendo o consumo de carne suína mal cozida o principal fator de risco para infecção. No Brasil, o HEV está presente em suínos e produtos derivados, havendo ainda poucos relatos de infecção em humanos, embora os estudos sorológicos apontem para uma prevalência bem maior. A ausência de triagem rotineira dificulta a compreensão dessa infecção em nosso meio fazendo-se necessária a inclusão desse agente como hipótese diagnóstica nos casos de hepatite aguda sem etiologia definida. Resultados: Paciente masculino, 67 anos, deu entrada no Hospital das Clínicas da FMUSP com quadro de hepatite aguda apresentando os seguintes sintomas: náusea, dor abdominal, urina escura e fezes claras. Os níveis de enzimas hepáticas estavam elevados (AST = 2.616 U/L; ALT = 2.654 U/L), fosfatase alcalina de 256 U/l, gama-glutamil transpeptidase de 210 U/l e bilirrubina total de 11,6 mg/dL. A tomografia de abdome apresentou fígado de dimensões um pouco aumentadas, de contornos regulares, sem evidência de lesões focais. A infecção pelos vírus das hepatites A, B ou C foi descartada por ausência de marcadores sorológicos dessas infecções. Foi realizada a pesquisa do HEV por PCR em tempo real sendo o RNA viral detectado com carga viral de 222,44 U/ul, além disso a sorologia para pesquisa de anticorpos anti-HEV IgM e IgG foi reagente. O genoma dessa cepa de HEV foi caracterizado e o genótipo classificado como 3 subtipo f (HEV-3f). Na análise filogenética essa sequência viral agrupou-se com cepas do HEV detectadas em suínos da região Nordeste do Brasil. Conclusão: No Brasil até o presente momento apenas o genótipo 3 do HEV foi identificado infectando humanos e suínos. Curiosamente, o paciente infectado pelo HEV identificado neste estudo tinha um histórico de viagem recente para a cidade de Garanhuns - Pernambuco, onde foi relatada alta soroprevalência de HEV em suínos. A estreita relação filogenética do HEV isolado do paciente com cepas suínas isoladas no referido estado, em cidades próximas de onde o paciente esteve, sugere uma possível transmissão zoonótica do HEV nesta região. O estudo da diversidade genética do HEV é de grande relevância para o entendimento das vias de transmissão predominantes em nosso meio e para a avaliação da eficácia dos métodos moleculares utilizados para diagnóstico.

Perivascular adipose tissue (PVAT) regulates vascular tonus with an anticontractile effect, which may be dysfunctional in hypertension. An Egg White Hydrolysate (EWH), a bioactive food, restores endothelium dysfunction and reduces blood pressure levels in malignant hypertension. We aimed to evaluate whether dietary supplementation with EWH interferes with the PVAT function in the mesenteric resistance arteries (MRA) of DOCA-salt hypertensive animals and the mechanisms involved. Male rats were divided into 4 groups and treated for 8 weeks. For 4 weeks, DOCA-salt or vehicle-treated rats (SHAM) were induced, and after that, some rats were co-treated with DOCA-salt or vehicle plus EWH (1 g/kg/day) for 4 weeks more. MRA and/or their PVAT (mPVAT) were used for functional, molecular, and biochemical analysis. The anticontractile effect of mPVAT in response to norepinephrine (NE) was observed only in MRA rings with PVAT of the SHAM group, while this effect was abolished in DOCA-salt rings. The EWH treatment did not change the anticontractile effect of mPVAT in SHAM but partially restored it in DOCA-salt rats. Acute aliskiren incubation reduced NE-induced contraction only in MRA with PVAT of DOCA-salt rats. EWH prevented the overactivation of the renin levels and ACE activity in mPVAT of DOCA-salt rats; while did not change AT1R expression, but increased AT2R expression. In mPVAT, EWH blocked the increase of MDA, ROS and pro-inflammatory cytokines observed in DOCA-salt rats. EWH improved PVAT dysfunction in MRA of severe hypertension. This beneficial effect could be mediated by an ameliorated redox balance, inflammatory state, and RAS axis.

The purpose of this study is to assess the cardiometabolic responses of a lifestyle intervention (LI) conducted at home among breast cancer (BC) survivors during the two years of COVID-19 pandemic. A 3-month LI focused on diet and exercise was performed on thirty BC survivors (women; stages 0-II; non-metastatic; aged 53.6 ± 7.6 years; non-physically active) with a risk factor related to metabolic/endocrine diseases. Anthropometrics, cardiorespiratory fitness (V˙ O2max), physical activity level (PAL), adherence to the Mediterranean diet (MeDiet modified questionnaire), and several biomarkers (i.e., glycemia, insulin, insulin resistance [HOMA-IR] index, triglycerides, high- [HDL] and low- [LDL] density lipoproteins, total cholesterol, progesterone, testosterone, and hs-troponin) were evaluated before and 3-, 6-, 12-, and 24-month after the LI. Beneficial effects of the LI were observed on several variables (i.e., body mass index, waist circumference, MeDiet, PAL, V˙ O2max, glycemia, insulin, HOMA-IR index, LDL, total cholesterol, triglycerides, testosterone) after 3-month. The significant effect on Mediterranean diet adherence and V˙ O2max persisted up to the 24-month follow-up. Decreases in HOMA-IR index and triglycerides were observed up to 12-month, however did not persist afterward. This study provides evidence on the positive association between LI and cardiometabolic health in BC survivors.

Introdução/Objetivo: As infecções por Pseudomonas aeruginosa produtora de Metalobetalactamases (MBL) se configuram como uma das maiores ameaças à saúde pública. Os controladores de infecção, hoje se deparam com o esgotamento terapêutico, especialmente, se há expressão de metalobetalactamase. Assim, o objetivo foi delinear o perfil epidemiológico, clínico e microbiológico dessas infecções, dos pacientes internados em um hospital universitário de referência do Brasil, nos anos de 2021 e 2022. Métodos: Os dados foram coletados a partir de prontuários de pacientes internados em leitos de enfermaria e de Unidade de Terapia Intensiva, que, também, tinham seu acompanhamento pelo time Stewardship iniciado e tabulados em um uma planilha específica. Analisou-se os seguintes parâmetros: sexo, idade, motivo da internação, unidade de hospitalização, tipo de cultura, uso de ventilação mecânica, gene de resistência, perfil de sensibilidade, tratamento e desfecho. Aprovado pelo Comitê de Ética n° 3.697.674. Resultados: Foram identificados 13 pacientes com infecções por P. aeruginosa produtora de MBL. O sexo masculino foi o mais acometido (92,3%) e a média de idade foi de 68,3 anos. As infecções do respiratórias foram as mais prevalentes (38,4%), doenças cardiovasculares (30,8%) e neoplasias (23,1%). A maioria dos pacientes estavam internados em Unidade de Terapia Intensiva (61,5%) e os demais na Clínica Médica (38,5%). Em 77% dos casos houve uso de ventilação mecânica. As culturas do trato respiratório foi o exame microbiológico mais prevalente (84,6%). Todas as cepas isoladas possuíam o gene de resistência da enzima Imipenemase. Os isolados se mostraram resistentes a praticamente todos os antibioticos disponíveis no Brasil. Os antibióticos mais capazes de combater essas infecções in vitro foram a Polixina B (77% de cepas sensíveis) e a amicacina (7,7% de cepas sensíveis). A maioria pacientes (53,8%) não recebeu nenhum tratamento, seja por óbito precoce ou por melhora clínica e laboratorial no momento do resultado da cultura. A polimixina B foi o fármaco mais utilizado, compondo, total ou parcialmente, a estratégia terapêutica de 38,5% das situações. A taxa de mortalidade foi de 61,5%. Conclusão: Conclui-se que o tratamento de pacientes acometidos por infecções por cepas de P. aeruginosa produtoras de MBL representa um grande desafio nos hospitais, pela escassez de ATM e gravidade dos casos. Ressalta-se a importância de buscar novos tratamentos para esses patógenos.

Objective: Investigate the influence of posterior crossbite on masticatory and swallowing functions by videofluoroscopy examination and to analyze the effects of Rapid Maxillary Expansion (RME) on the same functions. Methods: A prospective longitudinal study was conducted on 32 children, 21 of them with posterior crossbite (10 girls and 11 boys, mean age 9.2 years, study group) and 11 children with no occlusal changes (6 girls and 5 boys, mean age 9.3 years, control group). The children were evaluated by an orthodontist for diagnosis, group characterization and occlusal treatment, by the otorhinolaryngology team for the assessment of respiratory symptoms, and by a speech therapist for videofluoroscopic evaluation of masticatory and swallowing parameters. The children with posterior crossbite were treated orthodontic ally using the Haas disjunctor for approximately six months and re-evaluated 5-months after removal of the appliance. Data were analyzed statistically by the Studentt-test for independent samples for comparison of the crossbite and control groups before and after treatment. Results: There was no significant difference in oral preparatory and oral transit times, nor in cycles and masticatory frequency, between the pre and post orthodontic treatment groups and the control group. Conclusion: Rapid maxillary expansion did not influence the masticatory and swallowing variables studied by videofluoroscopy. However, the data require caution in interpretation.

Objective: The use of parenteral nutrition (PN) formulations that do not contain iodine can contribute to the deficiency of this mineral, potentially leading to hypothyroidism and, ultimately, neurocognitive impairments. This study aimed to evaluate TSH alterations in newborns receiving PN. Methods: Retrospective study of neonatal intensive care unit patients receiving PN for > 15 days. Nutritional, anthropometric, and biochemical variables (TSH, T4, CRP) were analyzed. Hypothyroidism was defined by TSH > 10 mU/L. Results: Two hundred newborns were evaluated [156 (78%) preterm, 31±5 weeks of gestational age, 112 (56%) with very or extremely low birth weight]. The median (IQR) hospital stay was 68 (42-110) days, PN duration was 31 (21-47) days, and 188 (94%) patients also received enteral nutrition. Overall, 143 (71.5%) newborns underwent at least one TSH measurement. The prevalence of hypothyroidism was 10.5%. The Median PN duration in this group was 51 (34-109) days. Among those with hypothyroidism, 10 received Lugol's solution and six levothyroxine. Thirteen patients received prophylactic Lugol's solution with a median PN duration of 63 (48-197) days. TSH levels correlated positively with PN duration (r = 0.19, p = .02). Conclusions: The present data suggest that changes in TSH and T4 levels are present in neonates receiving PN for > 15 days, suggesting this population may be at risk for developing hypothyroidism. Therefore, the authors suggest that TSH and T4 measurements should be included as routine in neonatal patients receiving PN for > 15 days if PN formulations are not supplemented with iodine, and that iodine supplementation be provided as necessary.

Adherence to secondary prevention measures after acute coronary syndrome (ACS) is essential to prevent disease recurrence. In Brazil, the Brazilian Unified Health System (SUS, in Portuguese), and the private healthcare system (PHCS) coexist. We aimed to evaluate the adherence to secondary prevention in patients with ACS who were assisted by either SUS or PHCS. In this longitudinal prospective study, patients with ACS were admitted to the four cardiological reference hospitals of Sergipe, three of which assisted PHCS users, and one, SUS users. We analyzed the two patient care models with multiple logistic regression models for adherence to physical activity, pharmacotherapy, and smoking cessation. We enrolled 581 volunteers in this study: 44.1 % from SUS and 55.9 % from PHCS. PHCS users showed greater adherence to pharmacotherapy at both 30 and 180 (p = 0.001) days after ACS with better results in all classes of medications (p

Dapagliflozin has been demonstrated to improve glycemic control, blood pressure, and body weight in type 2 diabetes mellitus (T2D); indeed, it can also reduce the risk of progression to renal failure, of hospitalization for heart failure and of cardiovascular death. We aim to investigate the acute effect of Dapagliflozin on kidney function in the common clinical practice in T2D. This is a study including 1402 patients with T2D recruited from 11 centers in Lombardia, Italy, who were evaluated at baseline and after 6 months of treatment with Dapagliflozin 10 mg per day. The primary outcome of the study was the change in HbA1c, while the secondary outcomes were modification of weight, BMI, systolic and diastolic pressure, creatinine, eGFR and albuminuria status. After 24 weeks of treatment with Dapagliflozin, a reduction in Hb1Ac was observed (−0.6 ± 1.8%) as well as in BMI (−1.5 ± 5.2 kg/m2). Statistically significant changes were also found for systolic and diastolic blood pressure, cholesterol and triglycerides. Interestingly, a statistically significant acute improvement of kidney function was evident. Our analyses confirm the beneficial effects of dapagliflozin after 6 months of therapy, with improvements of glycemic and lipid profiles, blood pressure, BMI. Finally, an acute positive effect on albuminuria and KIDGO classes was observed during a 6 months treatment with dapagliflozin in patients with T2D.

Introduction: Malnutrition is associated with an increased risk of complications in hospitalized patients, and parenteral nutrition (PN) is used when oral or enteral feeding is not possible. This study aimed at analyzing associations between PN characteristics and infectious complications in hospitalized patients. Material and methods: This was a retrospective cohort study conducted in a tertiarycare university hospital. Data from consecutive adult patients submitted to PN (January 2016 to December 2017; ICU and ward) were reviewed by means of an electronic database. Patient’s clinical characteristics, PN prescription and catheter insertion procedure data were extracted and analyzed. The main outcome was the development of central line–associated bloodstream infection (CLABSI). The secondary outcomes were other infectious complications and mortality, as well as factors associated with CLABSI. Results: We analyzed 165 patients and 247 catheters used for parenteral nutrition infusion. The CLABSI rate was 6.47 per 1000 catheter-days. In the univariable analysis, CLABSI was associated with longer hospitalization time, longer PN time, longer catheter time, catheter insertion performed by a surgeon or a surgical resident, and procedures performed outside the ICU. In an extended time-dependent Cox regression, no variable was associated with a higher risk of CLABSI, and additional PN days did not increase the rate of CLABSI. The overall mortality rate was 24.8%. Only the patients’ comorbidity index was associated with death in the multivariable analysis. Discussion: In our study, patients who needed PN had an overall CLABSI rate of 6.47 per 1000 catheter-days. These outcomes were not associated with PN and catheter characteristics studied after adjustment for catheter time. The overall mortality rate was 24.8% and it was not associated with PN in multivariable analyses, only with Charlson comorbidity index.

O tratamento da criptococose baseia-se na administração inicial de anfotericina B com flucitosina, seguida de fase de consolidação e manutenção com fluconazol. Uma alternativa é o uso do fluconazol em monoterapia ou terapia combinada com outros antifúngicos. Desse modo, o fluconazol é o antifúngico mais utilizado no tratamento da criptococose. O tratamento de manutenção com fluconazol poderia favorecer o risco por surgimento de cepas resistentes, cuja prevalência é de 20% no mundo. O objetivo desse trabalho é descrever um caso clínico de criptococose disseminada por Cryptococcus gatti com falha terapêutica inicial por provável resistência ao fluconazol. Homem, 27 anos, com antecedente pessoal de Síndrome de Alport, transplantado renal há 3 anos, com quadro agudo de cefaleia e febre e tomografia computadorizada (TC) de crânio, com aparente diminuição de sulcos e do 3º ventrículo à direita. Punção liquórica, com 40 células, com predomínio linfomononuclear, pesquisa de Cryptococcus spp. em tinta da China positiva e antígeno 1/1024. TC de tórax com múltiplos nódulos e massas pulmonares bilaterais de até 3,2 cm e biópsia pulmonar mostrando processo inflamatório crônico com estruturas compatíveis com Cryptococcus sp. Prescritos Anfotericina B Lipossomal e 5-Flucitosina, mas com manutenção de positividade em cultura de líquor para Cryptococcus gatti, mesmo após 45 dias de tratamento. Antifungigrama com MIC de 16 g/mL para Fluconazol, optada pela troca por Voriconazol, com posterior negativação de cultura liquórica. Paciente manteve quadro pulmonar, não responsivo à terapia convencional, evoluindo com pneumotórax espontâneo e fístula brônquica de alto débito, evoluindo com complicações clínicas e óbito após quatro meses de tratamento. A resistência à fluconazol na criptococose foi documentada pela primeira vez em 1993 com aumento progressivo de prevalência de resistência ao fluconazol. Há evidência para uma relação entre MIC < 16 g/mL e uma melhor resposta ao fluconazol em comparação a MIC ≥ 16. Embora não haja consenso sobre o ponto de corte dos testes de sensibilidade ao fluconazol, pacientes que não apresentam evolução favorável e MICs elevados, deve-se considerar a substituição do antifúngico. No caso em questão, o paciente apresentou cura microbiológica da neurocriptococose após a troca para o voriconazol, mas houve manutenção do quadro pulmonar pela dificuldade de abordagem cirúrgica, pelo risco de formação de novas fístulas e morbidade do procedimento.

Introdução: As bactérias multirresistentes, nos últimos anos, tornou-se um problema dos hospitais ao redor do mundo; a cada ano, a incidência de pacientes colonizados com este perfil de infecção cresce, se estabelecendo como uma pandemia de difícil resolução. Dentre estas, os gram negativos produtores de carbapenemases e as VRE (enterococcus resistentes a vancomicina) destacam-se por sua recorrência nos hospitais brasileiros. Por esse motivo, é imprescindível a identificação precoce desses microrganismos por meio dos laboratórios de microbiologia e serviços de vigilância em saúde institucionais para iniciar os devidos protocolos de prevenção, como isolamento desses pacientes, bem como orientações acerca do tratamento adequado. Objetivo: Identificar o perfil de resistência bacteriana dos pacientes isolados em um hospital universitário. Metodologia: Foram analisados 715 pacientes isolados por suspeita de bactérias multirresistentes de um Hospital Universitário no Ceará por meio de planilhas de isolamento entre janeiro de 2017 e agosto de 2021 acompanhados pelo Serviço de Controle de Infecção Hospitalar institucional. Resultados: Dentre os 715 pacientes isolados, em 310 (43,33%) foram identificados microrganismos gram negativos com perfil de resistência aos carbapenêmicos, dos quais 185 (59,67%) eram K. pneumoniae, 45 (14,51%) eram P. aeruginosas e 80 (25,8%) eram A. baumannii; em 168 (23,49%) foram identificados VRE e 44 (6,15%) gram negativos produtores de Metalo-β-Lactamases, estas, por sua vez, foram identificadas entre 2019 e 2021. Conclusão: Denota-se que a resistência a carbapenêmicos é o perfil mais recorrente das bactérias isoladas, sendo a K. pneumoniae com a maior incidência, isso implica em um maior desafio terapêutico, pois as opções no mercado brasileiro são limitadas, além disso, o número crescente de bactérias Metalo-β-Lactamases evidencia uma conjuntura preocupante, uma vez que não há quaisquer tratamento on-label para este perfil, elevando assim, o estado de alerta entre as instituições de saúde brasileira para essas bactérias.

Given the benefits of physical activity for breast cancer survivals, this pilot study aims to assess the feasibility of the MOTIVE program at achieving and maintaining the recommended physical activity level in women diagnosed and treated breast cancer, over 16 weeks. We conduct a pilot-controlled study of 20 women diagnosed with breast cancer stage I, II or IIIa. In this study, women of Intervention Arm (n = 10) received the MOTIVE program. This group was compared to women of Control Arm (n = 10) who received only counselling. Health-related fitness measures, and quality of life were assessed at baseline (t0) and after 4 (t1), 8 (t2) and 16 (t3) weeks. Intervention Arm women reached the recommended physical activity guidelines at t1 and t2 (eff.size = 1.9 [1.0–3.1]), and 90% continued to be active, autonomously, at t3 (eff.size = 1.12 [0.21–2.12]). Intervention Arm participants’ arm strength, fitness levels and quality of life also improved over time. No significant improvements in outcome measures were observed in Control Arm participants. These results are encouraging and suggest that the MOTIVE program may be a viable, well tolerated and effective option to help breast cancer women reaching a stable physical activity level over time, which meets prevention-related goals.

The electrochemical conversion of CO2 to high-value molecules is an elegant alternative for combining CO2 utilization with renewable energy conversion and storage. Herein we report the preparation and characterization of indium catalysts for the electrochemical CO2 reduction to formate. Indium coatings were prepared by electrodeposition from a deep eutectic solvent (DES) comprising 1:2 M choline chloride and ethylene glycol (12CE). The electrochemical behavior of indium chloride in this DES was investigated by cyclic voltammetry (CV) on copper, glassy carbon (GC) and platinum electrodes. The effect of InCl3 concentration, electrolyte temperature and deposition method on the phase and morphology of the coatings were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Indium deposits on copper and carbon were deployed as catalysts for the CO2 electrolysis in aqueous media. Chemical analysis by HPLC, GC, and NMR revealed an optimum efficiency toward formate at −1.9 V vs. Ag/AgCl. Indium coatings prepared by potentiostatic deposition showed faradaic efficiencies (FE) up to 72.5%. Gas diffusion electrodes (GDE) coated with indium led to formate concentrations up to 76 mM and formation rates of 0.183 mmol cm−2 h−1, which was considerably superior to indium coatings on planar electrodes. Keywords: Carbon dioxide utilization, Indium electrodeposition, Electrodeposition from deep eutectic solvents, Electrochemical CO2 reduction, Indium gas diffusion electrodes

As alterações de mastigação e de deglutição em crianças com hipertrofia adenoamigdaliana precisam ser melhor caracterizadas. OBJETIVO: Avaliar a frequência das alterações miofuncionais autorreportadas pelos pais, e se há diferenças entre os padrões de alterações entre crianças com hipertrofia adenoamigdaliana e as com hipertrofia apenas adenoideana. MÉTODO: Aplicação de questionário e avaliação clínica fonoaudiológica em crianças com hipertrofia de tonsilas com idade entre 3 e 6 anos. Os dados reportados pelos pais foram comparados com os dados obtidos pela avaliação fonoaudiológica; além disso, os dados das crianças com hipertrofia adenoamigdaliana foram comparados com as com hipertrofia adenoideana. Desenho científico: coorte transversal. RESULTADOS: As alterações miofuncionais observadas pela fonoaudióloga foram muito mais frequentes do que as reportadas pelos pais e não houve concordância entre os dois achados. As crianças com hipertrofia adenoideana e as com hipertrofia adenoamigdaliana apresentaram o mesmo padrão de alterações miofuncionais. CONCLUSÃO: Os pais relacionam pouco a hipertrofia de tonsilas a alterações na mastigação e na deglutição. A causa da obstrução respiratória parece não interferir no padrão de alteração miofuncional.

OBJETIVO: Avaliar a prevalência de atraso e fatores associados aos escores de desenvolvimento em crianças nascidas prematuras. MÉTODOS: Estudo transversal para avaliar o desenvolvimento por escalas Bayley III, incluindo-se prematuros de muito baixo peso de 18 a 24 meses de idade corrigida, acompanhados no Ambulatório de Prematuros da instituição. Excluíram-se: malformação congênita, síndrome genética, infecção congênita sintomática ao nascimento, surdez e cegueira. As variáveis numéricas foram comparadas por teste t de Student ou Mann-Whitney, e as categóricas, por qui-quadrado ou teste exato de Fisher. Para análise dos fatores associados aos escores de desenvolvimento, utilizou-se a regressão linear, considerando-se significante p < 0,05. RESULTADOS: Das 58 crianças avaliadas, quatro (6,9%) apresentaram alteração cognitiva; quatro (6,9%), motora; 17 (29,3%), de linguagem; 16 (27,6%), socioemocional; e 22 (37,9%), de comportamento adaptativo. À regressão linear múltipla, os fatores classe socioeconômica CDE (-13,27; IC95% -21,23 a -5,31) e dependência de oxigênio com 36 semanas de idade corrigida (-8,75; IC95% -17,10 a -0,39) diminuíram o escore cognitivo. A leucomalácia periventricular diminuiu o escore cognitivo (-15,21; IC95% -27,61 a -2,81), motor (-10,67; IC95% -19,74 a -1,59) e de comportamento adaptativo (-21,52; IC95% -35,60 a -7,44). O sexo feminino se associou ao maior escore motor (10,67; IC95% 2,77-12,97), de linguagem (15,74; IC95% 7,39-24,09) e socioemocional (10,27; IC95% 1,08-19,46). CONCLUSÕES: Prematuros de muito baixo peso apresentaram com maior frequência alterações na linguagem, comportamento adaptativo e socioemocional. As variáveis classe socioeconômica CDE, leucomalácia periventricular, displasia broncopulmonar e sexo masculino contribuíram para reduzir os escores de desenvolvimento.

OBJETIVOS: Descrever a metodologia de preparo de dois aditivos, líquido e em pó, derivados do leite humano e comparar a constituição com aditivo comercial FM85®. MÉTODOS: Foram utilizadas 40 amostras de leite humano para o preparo dos suplementos líquido e em pó. Ambos passaram por três fases de preparo: desnate, evaporação e retirada da lactose. Após essas fases, o suplemento líquido está pronto, e o em pó necessita da quarta fase - a liofilização. Em cada amostra dos suplementos líquido e em pó, foram adicionados, respectivamente, 80 mL (grupo I) e 100 mL (grupo II) de pool de leite humano de banco. Para comparação, 20 amostras de 100 mL do pool foram acrescidas de 5 g do suplemento FM85® (Nestlé) (grupo III). Realizaram-se análises de hidratos de carbono, proteína, lipídios, cálcio, fósforo, sódio, osmolalidade e conteúdo calórico, considerando diferença significativa p < 0,05. RESULTADOS: Os grupos I, II e III mostraram, respectivamente, os seguintes resultados: proteínas = 1,81, 2,38 e 1,96 g/dL (p < 0,001); hidratos de carbono = 6,70, 7,25 e 10,06 g/dL (p = 0,006); gordura = 3,75, 3,75 e 3,73 g/dL (p = 0,96); cálcio = 36,92, 44,75 e 79,37 mg/dL (p = 0,001); fósforo = 20,02, 23,28 e 56,30 mg/dL (p = 0,02); sódio = 14,32, 14,40 e 20,33 mEq/L (p = 0,143); osmolalidade = 391,45, 412,47 e 431, 00 mOsmol/kgH2O (p = 0,074); e conteúdo calórico = 67,78, 72,27 e 81,65 kcal (p = 0,001). CONCLUSÃO: Os aditivos estudados diferem significativamente do aditivo comercial FM85® em alguns de seus constituintes, e a sua constituição pode ou não atender às quantidades de nutrientes propostas pelas recomendações mais recentes.

Resumo: Contexto: A debilidade muscular tem impacto significativo na qualidade de vida do indivíduo com doença pulmonar obstrutiva crónica (DPOC), correlacionando-se com o número de exacerbações e a mortalidade. Medir a força muscular torna-se, portanto, de extrema importância. A ausência de padronização quanto ao número de séries e intervalo de recuperação no protocolo de avaliação isocinética pode gerar resultados díspares, dificultando a compreensão e a comparação a entre os estudos. Objectivo: Análise do efeito de duas séries e três intervalos de repouso na medida de força isocinética do quadríceps, a fim de identificar o protocolo adequado para a realização do teste. Métodos: Indivíduos com DPOC grave ou muito grave realizaram três testes isocinéticos para avaliação da musculatura extensora do joelho, à velocidade angular de 60°·sâ1, com intervalos de recuperação de 30, 60 ou 120 segundos. Cada teste consistiu em duas séries de cinco repetições, nas quais foram mensurados pico de torque, trabalho total e índice de fadiga. Resultados: Nos 20 indivíduos estudados (66,1±7,4 anos, 70±10,8 kg, 167,4±± 6,2 cm, VEF1 36,5±10,1% do predito) não houve diferença significativa nos valores de pico de torque, trabalho total e índice de fadiga, independente do número de séries ou da duração do intervalo de recuperação entre elas. Conclusão: Em indivíduos com DPOC grave ou muito grave, a força muscular do quadríceps pode ser avaliada por meio de protocolo isocinético composto por uma série de contracções com cinco repetições; se forem realizadas duas séries, 30 segundos de intervalo entre elas é suficiente para garantir a recuperação muscular.Rev Port Pneumol 2010; XVI (5): 717-736 Abstract: Rationale: Muscle debility has a significant impact on health-related quality of life in subjects with chronic obstructive pulmonary disease (COPD), and is correlated to exacerbation and even mortality. Assessing muscle strength is extremely relevant. Lack of standardisation in numbers of sets and rest interval in isokinetic test protocol can lead to distinct results, making comprehension and comparisons among studies difficult. Aim: To analyse the effect of two sets and three different rest intervals on isokinetic strength measurement of quadriceps tests, in order to define the adequate test protocol. Methods: Subjects with severe or very severe COPD underwent three isokinetic tests to evaluate knee extensor muscle strength, at an angular velocity of 60°·sâ1, with rest intervals of 30, 60 and 120 seconds. Each test consisted of two sets of five repetitions, during which peak torque, total work and fatigue index were measured. Results: In 20 studied subjects (66.1±7.4 years, 70±10.8 kg, 167.4±6.2 cm, FEV1 36.5±10.1%), there were no significant differences in peak torque, total work and fatigue index, independent of number of sets or rest interval between sets. Conclusion: In subjects with severe or very severe COPD, quadriceps muscle strength can be evaluated by an isokinetic protocol with one set of five repetitions. If two sets are performed, a rest interval of 30 seconds is enough to ensure muscle recovery between sets.Rev Port Pneumol 2010; XVI (5): 717-736 Palavras-chave: Doença pulmonar obstrutiva crónica, força muscular, teste isocinético, padrões de referência, Key-words: Chronic obstructive pulmonary disease, muscle strength, isokinetic test, reference standards

Contexto: A debilidade muscular tem impacto significativo na qualidade de vida do indivíduo com doença pulmonar obstrutiva crónica (DPOC), correlacionando-se com o número de exacerbações e a mortalidade. Medir a força muscular torna-se, portanto, de extrema importância. A ausência de padronização quanto ao número de séries e intervalo de recuperação no protocolo de avaliação isocinética pode gerar resultados díspares, dificultando a compreensão e a comparação a entre os estudos. Objectivo: Análise do efeito de duas séries e três intervalos de repouso na medida de força isocinética do quadríceps, a fim de identificar o protocolo adequado para a realização do teste. Métodos: Indivíduos com DPOC grave ou muito grave realizaram três testes isocinéticos para avaliação da musculatura extensora do joelho, à velocidade angular de 60°.s-1, com intervalos de recuperação de 30, 60 ou 120 segundos. Cada teste consistiu em duas séries de cinco repetições, nas quais foram mensurados pico de torque, trabalho total e índice de fadiga. Resultados: Nos 20 indivíduos estudados (66,1 ± 7,4 anos, 70 ± 10,8 kg, 167,4 ± ± 6,2 cm, VEF1 36,5 ± 10,1% do predito) não houve diferença significativa nos valores de pico de torque, trabalho total e índice de fadiga, independente do número de séries ou da duração do intervalo de recuperação entre elas. Conclusão: Em indivíduos com DPOC grave ou muito grave, a força muscular do quadríceps pode ser avaliada por meio de protocolo isocinético composto por uma série de contracções com cinco repetições; se forem realizadas duas séries, 30 segundos de intervalo entre elas é suficiente para garantir a recuperação muscular.Rationale: Muscle debility has a significant impact on health-related quality of life in subjects with chronic obstructive pulmonary disease (COPD), and is correlated to exacerbation and even mortality. Assessing muscle strength is extremely relevant. Lack of standardisation in numbers of sets and rest interval in isokinetic test protocol can lead to distinct results, making comprehension and comparisons among studies difficult. Aim: To analyse the effect of two sets and three different rest intervals on isokinetic strength measurement of quadriceps tests, in order to define the adequate test protocol. Methods: Subjects with severe or very severe COPD underwent three isokinetic tests to evaluate knee extensor muscle strength, at an angular velocity of 60°.s-1, with rest intervals of 30, 60 and 120 seconds. Each test consisted of two sets of five repetitions, during which peak torque, total work and fatigue index were measured. Results: In 20 studied subjects (66.1 ± 7.4 years, 70 ± 10.8kg, 167.4 ± 6.2cm, FEV1 36.5 ± 10.1%), there were no significant differences in peak torque, total work and fatigue index, independent of number of sets or rest interval between sets. Conclusion: In subjects with severe or very severe COPD, quadriceps muscle strength can be evaluated by an isokinetic protocol with one set of five repetitions. If two sets are performed, a rest interval of 30 seconds is enough to ensure muscle recovery between sets.

We evaluated the diagnostic performance of a Cryptosporidium immunoenzymatic assay (ELISA). Fecal samples were collected from 94 HIV-seropositive patients. All specimens were processed with a commercially-available ELISA to detect C. parvum specific coproantigen and with a modified Ziehl-Neelsen stain (ZNm) microscope exam. Overall, sensitivity of the immunoenzymatic test was 100%, with a specificity of 96%; positive and negative predictive values were 89% and 100%, respectively. The commercial ELISA and ZNm proved to be valuable diagnostic tools for Cryptosporidium infection.

Aims: Although accelerometer- and pedometer-based physical activity (PA) interventions can increase PA, there is no solid evidence for their benefits in patients with type 2 diabetes (T2DM). The aim of this systematic review and meta-analysis of randomized controlled clinical trials (RCTs) was to determine the effects of accelerometer- and pedometer-based PA interventions on hemoglobin A1c (HbA1c), fasting glucose, weight, BMI, blood pressure, lipids, and PA in adults with T2DM., Data Synthesis: Records from MEDLINE/PubMed, EMBASE, LILACS, and Scopus were searched from inception through March 28th, 2022. RCTs of at least two weeks of duration evaluated the effectiveness of pedometers or accelerometers as motivating tools for increasing PA in T2DM patients. This study was registered with PROSPERO and followed the PRISMA reporting guide. Of the 7131 non-duplicated articles retrieved, 24 RCTs (1969 patients) were included. The mean baseline HbA1c of the experimental group of included studies varied from 6.3 ± 0.9 % to 9.0 ± 0.01 %. The accelerometer- and pedometer-based PA interventions resulted in a greater improvement in HbA1c (-0.22 %; 95%CI, -0.4 % to -0.05 %; I 2  = 77 %) and triglycerides (-13.11 mg/dL; 95%CI, -25.21 to -1.02; I 2  = 22 %) versus control participants. Pedometer ambulatory use as a motivating tool significantly increased PA by 2,131 steps/day (95 % CI, 1,348 to 2,914; I 2  = 74 %) in T2DM patients., Conclusions: Pedometers and accelerometers are associated with reductions in HbA1c and triglycerides when used as motivating tools. Larger and higher-quality studies are required to determine the full effects of PA as motivated by trackers in T2DM population., Competing Interests: Conflicts of interest The authors have nothing to disclose., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: Vascular dysfunction and elevated circulating dipeptidyl peptidase 4 (DPP4) activity are both reported to be involved in the progression of heart failure (HF). While the cardiac benefits of DPP4 inhibitors (DPP4i) have been extensively studied, little is known about the effects of DPP4i on vascular dysfunction in nondiabetic HF. This study tested the hypothesis that vildagliptin (DPP4i) mitigates aortic hyperreactivity in male HF rats., Materials and Methods: Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation to HF induction or sham operation (SO). Six weeks after surgery, radiofrequency-ablated rats who developed HF were treated with vildagliptin (120 mg⸱kg -1 ⸱day -1 ) or vehicle for 4 weeks. Thoracic aorta reactivity, dihydroethidium fluorescence, immunoblotting experiments, and enzyme-linked immunosorbent assays were performed., Key Findings: DPP4i ameliorated the hypercontractility of HF aortas to the α-adrenoceptor agonist phenylephrine towards SO levels. In HF, the reduced endothelium and nitric oxide (NO) anticontractile effect on phenylephrine response was restored by DPP4i. At the molecular level, this vasoprotective effect of DPP4i was accompanied by (i) reduced oxidative stress and NADPH oxidase 2 (Nox2) expression, (ii) enhanced total endothelial nitric oxide synthase (eNOS) expression and phosphorylation at Ser1177, and (iii) increased PKA activation, which acts upstream of eNOS. Additionally, DPP4i restored the higher serum angiotensin II concentration towards SO., Significance: Our data demonstrate that DPP4i ameliorates aortic hypercontractility, most likely by enhancing NO bioavailability, showing that the DPP4i-induced cardioprotection in male HF may arise from effects not only in the heart but also in conductance arteries., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests associated with the manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Blood vessels are surrounded by perivascular adipose tissue (PVAT), which plays an important role in vascular tonus regulation due to its anticontractile effect; however, this effect is impaired in obesity. We previously demonstrated that miRNA-22 is involved in obesity-related metabolic disorders. However, the impact of miRNA-22 on vascular reactivity and PVAT function is unknown., Aim: To investigate the role of miRNA-22 on vascular reactivity and its impact on obesity-induced PVAT dysfunction., Main Methods: Wild-type and miRNA-22 knockout (KO) mice were fed a control or a high-fat (HF) diet. To characterize the vascular response, concentration-responses curves to noradrenaline were performed in PVAT- or PVAT+ thoracic aortic rings in absence and presence of L-NAME. Expression of adipogenic and thermogenic markers and NOS isoforms were evaluated by western blotting or qPCR., Key Findings: HF diet and miRNA-22 deletion reduced noradrenaline-induced contraction in PVAT- aortic rings. Additionally, miRNA-22 deletion increased noradrenaline-induced contraction in PVAT+ aortic rings without affecting its sensitivity; however, this effect was not observed in miRNA-22 KO mice fed a HF diet. Interestingly, miRNA-22 deletion reduced the contraction of aortic rings to noradrenaline via a NOS-dependent mechanism. Moreover, HF diet abolished the NOS-mediated anticontractile effect of PVAT, which was attenuated by miRNA-22 deletion. Mechanistically, we found that PVAT from miRNA-22 KO mice fed a HF diet presented increased protein expression of nNOS., Significance: These results suggest that miRNA-22 is important for aorta reactivity under physiological circumstances and its deletion attenuates the loss of the NOS-mediated anticontractile effect of PVAT in obesity., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Indigenous Brazilian peoples have faced an unparalleled increase in the rate of cardiovascular diseases following rapid nutritional transition to more urban diets. We aimed to conduct a systematic review and meta-analysis to evaluate the association between urbanisation (including data from Amazon rainforest deforestation) and cardiometabolic risk factors and outcomes., Methods: In this systematic review and meta-analysis, we searched Pubmed, Embase, Web of Science, and Scopus for articles published in any language between the year 1950 and March 10, 2022. Studies conducted in Indigenous Brazilian adults that evaluated metabolic health were included. Data for deforestation was obtained by the Amazon Deforestation Monitoring Project. Cardiovascular mortality was obtained from the Brazilian Health registry. Two independent reviewers evaluated studies for risk of bias, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The main outcomes assessed were the prevalence of obesity and related cardiometabolic risk factors among Indigenous Brazilian peoples and its association with urbanisation. Summary data were extracted from published reports for the meta-analyses. We calculated pooled estimates of the prevalence of each cardiometabolic outcome by using a random-effects model (DerSimonian-Laird method). This study is registered with the International Prospective Register of Systematic Reviews, CRD42021285480., Findings: 46 studies were identified, including a total of 20 574 adults from at least 33 Indigenous Brazilian ethnicities. Meta-analyses of the prevalence of obesity showed that there were higher rates of obesity (midwest region: 23% [95% CI 17-29]; and south region 23% [13-34]) and hypertension (south region: 30% [10-50]) in Indigenous peoples living in urban regions of Brazil, while the lowest rates of obesity (11% [95% CI 8-15]) and hypertension (1% [1-2]) were observed in those in the less urbanised (north) regions of Brazil. The prevalence of obesity was 3·5 times higher in participants living in urbanised Indigenous territories (28%) than in those living in lands with >80% native Amazon rainforest (8%). In meta-analyses that evaluated blood pressure level, there was no incremental change in blood pressure with ageing in Indigenous peoples who lived according to traditional lifestyle, in contrast to those living in urbanised regions. For Indigenous men with traditional lifestyles, systolic blood pressure changed from 109·8 mm Hg to 104·4 mm Hg between the youngest (<30 years) and the oldest (>60 years) age groups, and diastolic blood pressure changed from 69·8 mm Hg to 66·1 mm Hg. For Indigenous women with traditional lifestyles, systolic blood pressure was 100·0 mm Hg for the youngest age group with no changes for older age groups, and diastolic blood pressure was 62 mm Hg for the youngest age group with no changes for older age groups. For Indigenous men with urbanised lifestyles, systolic blood pressure changed from 117·3 mm Hg to 124·9 mm Hg between the youngest and the oldest age groups, and diastolic blood pressure changed from 72·7 mm Hg to 76·4 mm Hg. For Indigenous women with urbanised lifestyles, systolic blood pressure changed from 110·0 mm Hg to 116·0 mm Hg between the youngest and the oldest age groups, and diastolic blood pressure changed from 68·3 mm Hg to 74·0 mm Hg. For the years 1997 and 2019, the cardiovascular mortality rate in individuals living in the southeast region (the most urbanised) was 2·5 times greater than that observed in the north. Conversely, the incremental rise in cardiovascular mortality in the past two decades among Indigenous Brazilians living in the north or northeast (2·7 times increase) stands in stark contrast to the stable rates in those living in already urbanised regions., Interpretation: The macrosocial changes of Indigenous peoples' traditional ways of living consequent to urbanisation are associated with an increased prevalence of adverse cardiometabolic outcomes. These data highlight the urgent need for environmental policies to ensure the conservation of the natural ecosystem within Indigenous territories, as well as the development of socio-health policies to improve the cardiovascular health of Indigenous Brazilians peoples living in urban areas., Funding: None., Competing Interests: Declaration of interests CKK reports research grants from Boehringer Ingelheim, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: The lung is an important target organ damage in intestinal ischemia/reperfusion (II/R), but mechanisms involved in II/R-induced pulmonary artery (PA) dysfunction, as well as its treatment, are not clear. The present study aimed to investigate the mechanisms involved in the II/R-induced PA dysfunction and a possible protective role of acute simvastatin pretreatment., Main Methods: Male Wistar rats were subjected to occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion (II/R) or sham-operated surgery (sham). In some rats, simvastatin (20 mg/kg, oral gavage) was administrated 1 h before II/R., Key Findings: II/R reduced acetylcholine-induced relaxation and phenylephrine-induced contraction of PA segments, which were prevented by acute simvastatin pretreatment in vivo or restored by inducible nitric oxide synthase (iNOS) inhibition in situ with 1400 W. Elevated reactive oxygen species (ROS) levels and higher nuclear translocation of nuclear factor kappa B (NFκB) subunit p65 were observed in PA of II/R rats and prevented by simvastatin. Moreover, simvastatin increased superoxide dismutase (SOD) activity and endothelial nitric oxide synthase (eNOS) expression in PA of the II/R group as well as prevented the increased levels of interleukin (IL)-1β and IL-6 in lung explants following II/R., Significance: The study suggests that pretreatment with a single dose of simvastatin prevents the II/R-induced increase of inflammatory factors and oxidative stress, as well as PA endothelial dysfunction and adrenergic hyporreactivity. Therefore, acute simvastatin administration could be therapeutic for pulmonary vascular disease in patients suffering from intestinal ischemic events., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Nitric oxide synthases (NOSs) are key enzymes regulating vascular function. Previously, we reported that β-adrenergic (β-AR) overstimulation, a common feature of cardiovascular diseases, did not impair endothelium-dependent vasodilation, although it resulted in endothelial NOS (eNOS) uncoupling and reduced NO bioavailability. In addition to NO, neuronal NOS (nNOS) produces H 2 O 2 , which contributes to vasodilation. However, there is limited information regarding vascular β-AR signaling and nNOS. In the present study, we assessed the possible role of nNOS-derived H 2 O 2 and caveolins on endothelial vasodilation function following β-AR overstimulation., Main Methods: Male C57BL/6 wild-type and nNOS knockout mice (nNOS -/- ) were treated with the β-AR agonist isoproterenol (ISO, 15 mg·kg -1 ·day -1 , s.c.) or vehicle (VHE) for seven days. Relaxation responses of aortic rings were evaluated using wire myograph and H 2 O 2 by Amplex Red., Key Findings: Acetylcholine- or calcium ionophore A23187-induced endothelium-dependent relaxation was similar in aortic rings from VHE and ISO. However, this relaxation was significantly reduced in aortas from ISO compared to VHE when (1) caveolae were disrupted, (2) nNOS was pharmacologically inhibited or genetically suppressed and (3) H 2 O 2 was scavenged. NOS-derived H 2 O 2 production was higher in the aortas of ISO mice than in those of VHE mice. Aortas from ISO-treated mice showed increased expression of caveolin-1, nNOS and catalase, while caveolin-3 expression did not change., Significance: The results suggest a role of caveolin-1 and the nNOS/H 2 O 2 vasodilatory pathway in endothelium-dependent relaxation following β-AR overstimulation and reinforce the protective role of nNOS in cardiovascular diseases associated with high adrenergic tone., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Parenteral nutrition (PN) is an available option for nutritional therapy and is often required in the hospital setting to overcome malnutrition., Objectives: The aim of this study was to assess whether PN is associated with an increased risk of mortality or infectious complications in all groups of hospitalized patients compared with those receiving other nutritional support strategies., Methods: For this systematic review and meta-analysis MEDLINE, Embase, Cochrane Central, Scopus, clinicaltrials.gov, and Web of Science were searched for randomized controlled trials (RCTs) and observational studies with parallel groups that explored the effect of PN on mortality and infectious complications, published until March 2021. Two independent reviewers extracted the data and assessed the risk of bias. Fixed-effects meta-analysis was performed to compare the groups from RCTs. Trial sequential analysis (TSA) was used to identify whether the results were sufficient to reach definitive conclusions., Results: Of the 83 included studies that compared patients receiving PN with those receiving other strategies, 67 RCTs were included in the meta-analysis. PN was not associated with a higher risk of mortality (RR: 1.01; 95% CI: 0.95, 1.07). On the other hand, PN was associated with a higher risk of infectious events (RR: 1.23; 95% CI: 1.12, 1.36). PN was specifically associated with abdominal infection and catheter infection. The TSA showed that there were sufficient data to make numerical conclusions about mortality, any infectious event, and abdominal infectious complications., Conclusions: This study suggests that although PN is not associated with greater mortality in hospitalized patients, it is associated with infectious complications. Through TSA, definite conclusions about survival and infection rates could be made.This review was registered at www.crd.york.ac.uk/prospero/ as CRD42018075599., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Uncoupling protein 2 (UCP2) plays an important role in energy expenditure regulation. Previous studies have associated the common -866G/A (rs659366) and Ins/Del polymorphisms in the UCP2 gene with metabolic and obesity-related phenotypes. However, it is still unclear whether these polymorphisms influence weight loss after bariatric surgery., Objectives: To investigate whether UCP2 -866G/A and Ins/Del polymorphisms are associated with weight loss outcomes after bariatric surgery., Setting: Longitudinal study in a university hospital., Methods: We retrospectively evaluated 186 patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for clinical and laboratory characteristics in the preoperative period, 6, 12, and 18 months after RYGB. The -866G/A (rs659366) polymorphism was genotyped using real-time PCR, while the Ins/Del polymorphism was genotyped by direct separation of PCR products in 2.5% agarose gels., Results: Patients with the -866A/A genotype showed higher body mass index (BMI) after 6, 12, and 18 months of surgery and excess body weight after 6 and 12 months compared with G/G patients. They also showed lower excess weight loss (EWL%) after 6 and 12 months of surgery. Ins allele carriers (Ins/Ins + Ins/Del) had lower delta (Δ) BMI 12 months after surgery compared with Del/Del patients. Accordingly, patients carrying haplotypes with ≥2 risk alleles of these polymorphisms had higher BMI and excess weight and lower EWL% during follow-up., Conclusion: UCP2 -866A/A genotype is associated with higher BMI and excess weight and lower EWL% during an 18-month follow-up of patients who underwent RYGB, while the Ins allele seems to be associated with lower ΔBMI 12 months after surgery. Further studies are needed to confirm the associations of the -866G/A and Ins/Del polymorphisms with weight loss after bariatric surgery., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Critically ill patients with body mass index (BMI) < 20 kg/m 2 have worse outcomes than normal/overweight patients possibly because underweight is a marker of malnutrition. To assess the effects of nutrition therapy in this population during the first week of an ICU stay., Methods: Prospective, 2-centre, observational study. Nutritional evaluations were performed between days 2 and 3 (first) and between days 5 and 7 (second) of ICU admission. In the first evaluation, patients were divided into non-fed (without nutritional support) and early-fed (those already receiving nutritional support) groups. In the second evaluation, patients were divided according to caloric intake (≥or<20 kcal/kg) and protein intake (≥or<1.3 g of protein/kg)., Results: Of the 4236 patients screened and 342 were included in the cohort. Mortality was 58.5% (median 21 [11-38.25] days of follow-up). Unadjusted patient survival was worse in the non-fed group than in the early-fed group (HR 1.66; 95%CI, 1.18 to 2.32). There was no difference in mortality between groups after adjusting for the SOFA score on the day of the evaluation. At the second evaluation, unadjusted analysis showed better in-hospital survival in patients with higher caloric (HR0.58; 95%CI, 0.40 to 0.86) and protein intake (HR0.59; 95%CI, 0.42 to 0.82); there was no association between mortality and caloric or protein intake after adjusting for the SOFA score on the day of the evaluation., Conclusion: Nutritional therapy in the first week of ICU stay did not affect vital outcome after adjusting for the SOFA score on the day of the evaluation in underweight critically ill patients., Clinical Trial Registry: ClinicalTrials.gov number NCT03398343., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The amount and quality of carbohydrates are important determinants of plasma glucose after meals. Regarding fiber content, it is unclear whether the intake of soluble fibers from foods or supplements has an equally beneficial effect on lowering postprandial glucose. Objective: The aim of our study was to compare the acute effect of soluble fiber intake from foods or supplements after a common meal on postprandial plasma glucose and plasma insulin in patients with type 2 diabetes (T2D). Design: A randomized crossover clinical trial was conducted in patients with T2D. Patients consumed isocaloric breakfasts (mean ± SD: 369.8 ± 9.4 kcal) with high amounts of fiber from diet food sources (total fiber: 9.7 g; soluble fiber: 5.4 g), high amounts of soluble fiber from guar gum supplement (total fiber: 9.1 g; soluble fiber: 5.4 g), and normal amounts of fiber (total fiber: 2.4 g; soluble fiber: 0.8 g). Primary outcomes were postprandial plasma glucose and insulin (0-180 min). Data were analyzed by repeated measures ANOVA and post hoc Bonferroni test. Results: A total of 19 patients [aged 65.8 ± 7.3 y; median (IQR), 10 (5-9) y of T2D duration; glycated hemoglobin 7.0% ± 0.8%; body mass index (in kg/m 2 ) 28.2 ± 2.9] completed 57 meal tests. After breakfast, the incremental area under the curve (iAUC) for plasma glucose [mg/dL · min; mean (95% CI)] did not differ between high fiber from diet (HFD) [7861 (6257, 9465)] and high fiber from supplement (HFS) [7847 (5605, 10,090)] ( P = 1.00) and both were lower than usual fiber (UF) [9527 (7549, 11,504)] ( P = 0.014 and P = 0.037, respectively). iAUCs [μIU/mL · min; mean (95% CI)] did not differ ( P = 0.877): HFD [3781 (2513, 5050)], HFS [4006 (2711, 5302), and UF [4315 (3027, 5603)]. Conclusions: Higher fiber intake was associated with lower postprandial glucose at breakfast, and the intake of soluble fiber from food and supplement had a similar effect in patients with T2D. This trial was registered at clinicaltrials.gov as NCT02204384., (© 2017 American Society for Nutrition.)

Objectives: This study aimed to assess 6-month outcomes in patients with implantable cardioverter-defibrillators (ICDs) undergoing renal sympathetic denervation (RSD) for refractory ventricular arrhythmias (VAs)., Background: ICDs are generally indicated for patients at high risk of malignant VAs. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of VAs., Methods: A total of 10 patients with refractory VA underwent RSD. Underlying conditions were Chagas disease (n = 6), nonischemic dilated cardiomyopathy (n = 2), and ischemic cardiomyopathy (n = 2). Information on the number of ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes and device therapies (antitachycardia pacing/shocks) in the previous 6 months as well as 1 and 6 months post-treatment was obtained from ICD interrogation., Results: The median number of VT/VF episodes/antitachycardia pacing/shocks 6 months before RSD was 28.5 (range 1 to 106)/20.5 (range 0 to 52)/8 (range 0 to 88), respectively, and was reduced to 1 (range 0 to 17)/0 (range 0 to 7)/0 (range 0 to 3) at 1 month and 0 (range 0 to 9)/0 (range 0 to 7)/0 (range 0 to 3) at 6 months afterward, respectively. There were no major procedure-related complications. Two patients experienced sustained VT within the first week; in both cases, no further episodes occurred during follow-up. Two patients were nonresponders: 1 with persistent idioventricular rhythm and 1 with multiple renal arteries and incomplete ablation. Three patients died during follow-up. None of the deaths was attributed to VA., Conclusions: In patients with ICDs and refractory VAs, RSD was associated with reduced arrhythmic burden with no procedure-related complications. Randomized controlled trials investigating RSD for treatment of refractory VAs in patients with increased sympathetic activity are needed., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to investigate whether β-adrenoceptor (β-AR) overstimulation induced by in vivo treatment with isoproterenol (ISO) alters vascular reactivity and nitric oxide (NO) production and signaling in pulmonary arteries., Main Methods: Vehicle or ISO (0.3mgkg(-1)day(-1)) was administered daily to male Wistar rats. After 7days, the jugular vein was cannulated to assess right ventricular (RV) systolic pressure (SP) and end diastolic pressure (EDP). The extralobar pulmonary arteries were isolated to evaluate the relaxation responses, protein expression (Western blot), NO production (diaminofluorescein-2 fluorescence), and cyclic guanosine 3',5'-monophosphate (cGMP) levels (enzyme immunoassay kit)., Key Findings: ISO treatment induced RV hypertrophy; however, no differences in RV-SP and EDP were observed. The pulmonary arteries from the ISO-treated group showed enhanced relaxation to acetylcholine that was abolished by the NO synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (l-NAME); whereas relaxation elicited by sodium nitroprusside, ISO, metaproterenol, mirabegron, or KCl was not affected by ISO treatment. ISO-treated rats displayed enhanced endothelial NOS (eNOS) and vasodilator-stimulated phosphoprotein (VASP) expression in the pulmonary arteries, while phosphodiesterase-5 protein expression decreased. ISO treatment increased NO and cGMP levels and did not induce eNOS uncoupling., Significance: The present data indicate that β-AR overactivation enhances the endothelium-dependent relaxation of pulmonary arteries. This effect was linked to an increase in eNOS-derived NO production, cGMP formation and VASP content and to a decrease in phosphodiesterase-5 expression. Therefore, elevated NO bioactivity through cGMP/VASP signaling could represent a protective mechanism of β-AR overactivation on pulmonary circulation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Acute brachial plexus neuropathy is characterized by acute onset of shoulder girdle and arm pain, followed by weakness of the shoulder and arm muscles. It affects primarily nerves of the upper trunk of the brachial plexus and the long thoracic nerve. Cranial nerve involvement is an infrequent association and implies a diagnostic challenge. We report a unique case of acute brachial plexus neuropathy with involvement of the cranial nerves IX, X, XI and XII., Case Report: Fifty six year-old woman who developed acute dysphonia, dysphagia and left shoulder pain, followed, six days later, by left arm weakness. Needle examination showed only fibrillation potentials and positive sharp waves in the left deltoid muscle. MRI of the brachial plexus shows enlargement of the trunks, cords and terminal branches, with mild gadolinium enhancement., Discussion: This case illustrates the unique presentation of neuralgic amyotrophy with involvement of nerves outside the brachial plexus, and the importance of MRI for diagnosis, in the absence of electrophysiologic involvement., (© 2013 Elsevier B.V. All rights reserved.)

Background/objectives: Therapy using bone marrow (BM) cells has been tested experimentally and clinically due to the potential ability to restore cardiac function by regenerating lost myocytes or increasing the survival of tissues at risk after myocardial infarction (MI). In this study we aimed to evaluate whether BM-derived mononuclear cell (MNC) implantation can positively influence the post-MI structural remodeling, contractility and Ca(2+)-handling proteins of the remote non-infarcted tissue in rats., Methods and Results: After 48 h of MI induction, saline or BM-MNC were injected. Six weeks later, MI scars were slightly smaller and thicker, and cardiac dilatation was just partially prevented by cell therapy. However, the cardiac performance under hemodynamic stress was totally preserved in the BM-MNC treated group if compared to the untreated group, associated with normal contractility of remote myocardium as analyzed in vitro. The impaired post-rest potentiation of contractile force, associated with decreased protein expression of the sarcoplasmic reticulum Ca(2+)-ATPase and phosphorylated-phospholamban and overexpression of Na(+)/Ca(2+) exchanger, were prevented by BM-MNC, indicating preservation of the Ca(2+) handling. Finally, pathological changes on remodeled remote tissue such as myocyte hypertrophy, interstitial fibrosis and capillary rarefaction were also mitigated by cell therapy., Conclusions: BM-MNC therapy was able to prevent cardiac structural and molecular remodeling after MI, avoiding pathological changes on Ca(2+)-handling proteins and preserving contractile behavior of the viable myocardium, which could be the major contributor to the improvements of global cardiac performance after cell transplantation despite that scar tissue still exists., (© 2013.)

Neurally mediated reflex syncope, more commonly known as vasovagal syncope (VVS), remains the most common cause of transient loss of consciousness and syncope in all age groups. Most evidence assessing treatment of VVS derived from randomized clinical trials is limited. Multiple modalities of both nonpharmacologic and pharmacologic strategies have been tested, with conflicting results. The treatment of VVS has been directed toward interventions that interrupt the reflex response at different levels, hypothetically preventing the onset of syncope. This article reviews the available evidence of the different nonpharmacologic and pharmacologic therapies available for the treatment of recurrent VVS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: Na(+), K(+)-ATPase activity contributes to the regulation of vascular contractility and it has been suggested that vascular Na(+), K(+)-ATPase activity may be altered during the progression of diabetes; however the mechanisms involved in the altered Na(+), K(+)-ATPase activity changes remain unclear. Thus, the aim of the present study was to evaluate ouabain-sensitive Na(+), K(+)-ATPase activity and the mechanism(s) responsible for any alterations on this activity in aortas from 1- and 4-week streptozotocin-pretreated (50 mg kg(-1), i.v.) rats., Main Methods: Aortic rings were used to evaluate the relaxation induced by KCl (1-10mM) in the presence and absence of ouabain (0.1 mmol/L) as an index of ouabain-sensitive Na(+), K(+)-ATPase activity. Protein expression of COX-2 and p-PKC-betaII in aortas were also investigated., Key Findings: Ouabain-sensitive Na(+), K(+)-ATPase activity was unaltered following 1-week of streptozotocin administration, but was increased in the 4-week diabetic aorta (27%). Endothelium removal or nitric oxide synthase inhibition with l-NAME decreased ouabain-sensitive Na(+), K(+)-ATPase activity only in control aortas. In denuded aortic rings, indomethacin, NS-398, ridogrel or Gö-6976 normalized ouabain-sensitive Na(+), K(+)-ATPase activity in 4-week diabetic rats. In addition, COX-2 (51%) and p-PKC-betaII (59%) protein expression were increased in 4-week diabetic aortas compared to controls., Significance: In conclusion, diabetes led to a time-dependent increase in ouabain-sensitive Na(+), K(+)-ATPase activity. The main mechanism involved in this activation is the release of TxA(2)/PGH(2) by COX-2 in smooth muscle cells, linked to activation of the PKC pathway., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Spleen or spleen plus bone marrow cells from (BALB/cxC57Bl/6)F1 donors were transferred into BALB/c recipients 21 days before skin or cardiac transplantation. Prolonged graft survival was observed on recipients treated with the mixture of donor-derived cells as compared to those treated with spleen cells alone. We evaluated the expression of CD45RB and CD44 by splenic CD4+ and CD8+ T cells 7 and 21 days after donor cell transfer. The populations of CD8+CD45RBlow and CD8+CD44high cells were significantly decreased in mice pre-treated with donor spleen and bone marrow cells as compared to animals treated with spleen cells only, although these cells expanded in both groups when compared to an earlier time-point. No differences were observed regarding CD4+ T cell population when recipients of donor-derived cells were compared. An enhanced production of IL-10 was observed seven days after transplantation in the supernatants of spleen cell cultures of mice treated with spleen and bone marrow cells. Taken together these data suggest that donor-derived bone marrow cells modulate the sensitization of the recipient by semi-allogeneic spleen cells in part by delaying the generation of activated/memory CD8+ T cells leading to enhanced graft survival.

Chronic ouabain treatment produces hypertension acting on the central nervous system and at vascular levels. However, cardiac effects in this model of hypertension are still poorly understood. Hence, the effects of hypertension induced by chronic ouabain administration ( approximately 8 microg day(-1), s.c.) for 5 weeks on the cardiac function were studied in Wistar rats. Ouabain induces hypertension but not myocardial hypertrophy. Awake ouabain-treated rats present an increment of the left ventricular systolic pressure and of the maximum positive and negative dP/dt. Isolated papillary muscles from ouabain-treated rats present an increment in isometric force, and this effect was present even when inotropic interventions (external Ca(2+) increment and increased heart rate) were performed. However, the sarcoplasmic reticulum activity and the SERCA-2 protein expression did not change. On the other hand, the activity of myosin ATPase increased without changes in myosin heavy chain protein expression. In addition, the expression of alpha(1) and alpha(2) isoforms of Na(+), K(+)-ATPase also increased in the left ventricle from ouabain-hypertensive rats. The present results showed positive inotropic and lusitropic effects in hearts from awake ouabain-treated rats, which are associated with an increment of the isometric force development and of the activity of myosin ATPase and expression of catalytic subunits of the Na(+), K(+)-ATPase.

Objective: To obtain and analyze the electrocardiogram and systolic blood pressure of cats before, during, and after a continuous infusion of propofol., Study Design: Prospective, uncontrolled experimental trial., Animals: Twenty healthy adult crossbred male and female cats aged between 3 and 5 years, weighing 2.8-5.0 kg (mean 3.9 kg)., Methods: Cats were pre-medicated with acepromazine 0.1 mg kg(-1) subcutaneously and anesthesia was induced with intravenous (IV) propofol 6 mg kg(-1) and maintained with a continuous infusion of propofol at 0.5 mg kg(-1) minute(-1) for 60 minutes. Electrocardiographic parameters and systolic blood pressure obtained by Doppler ultrasound were recorded before pre-medication (T0), 30 (T30), and 60 (T60) minutes after beginning the continuous infusion, and 30 minutes after its cessation (T90). Repeated measures anova was used to perform statistical analysis., Results: A significant decrease in heart rate was observed at all time points when compared with T0 values. The PR interval increased significantly at T60 and T90. Systolic blood pressures during anesthesia were significantly lower than at T0 and T90., Conclusion and Clinical Relevance: The changes seen were not clinically important in normal cats but given the reduction in heart rate and systolic blood pressure, careful consideration should be given before using this technique in patients in which hypotension or a reduction in heart rate would be poorly tolerated.

L-NAME (LN) induces hypertension by blocking nitric oxide (NO) synthesis. It produces vascular hyperreactivity to phenylephrine (PHE) associated with a reduced vascular Na+, K+-ATPase activity. The aim of this work was to investigate whether products of the cyclooxygenase pathway are involved in alterations of vascular reactivity and Na+-pump activity in the tail artery from LN-induced hypertension rats. Four groups of rats were used: Control (CT, normotensive), LN (50 mg/kg/day, hypertensive), indomethacin (Indo-4 mg/kg/day, normotensive), and LN plus Indo (LN + Indo, partially prevented hypertension). All drugs were administered in drinking water during 7 days. In isolated rat tail vascular beds; the reactivity to PHE, acetylcholine (ACh), sodium nitroprusside (SNP), the functional activity of the Na+, K+-ATPase (K+-induced relaxation) and the modulation of PHE-induced vasoconstriction by constitutively available NO were evaluated. LN increased vascular sensitivity (pD2) and reactivity (Emax) to PHE and Indo blocked the effect of LN on Emax without changing pD2. Emax and pD2 values for ACh were reduced by LN and partially reverted by Indo. SNP-induced vasodilatation was similar in all groups. LN reduced the activity of Na+, K+-ATPase and Indo prevented LN effects. LN also abolished NO ability to modulate PHE-induced contractions. This effect was partially prevented by Indo suggesting that products from the cyclooxygenase pathway might reduce NO actions. Indo itself did not affect vascular reactivity to PHE, ACh or SNP or the Na+,K+-ATPase activity. Results suggested that products from cyclooxygenase pathway are involved in the genesis or maintenance of LN-induced hypertension, playing a role in the increased vascular reactivity, in the reduction of the endothelium-dependent relaxation and in the inhibition of the functional activity of the Na+, K+-ATPase.