Two-way attack on IAPP proteotoxicity with implications for diabetes

Funding Information: This study was supported by FCT–Fundação para a Ciência e a Tecnologia (grants UIDB/04567/2020 and UIDP/ 04567/2020 to CBIOS, PTDC/BIA-MOL/31104/2017, and PhD grants PD/BD/135504/2018 to AFR and UI/BD/151421/2021 to SF. RM is funded by FCT Scientific Employment Stimulus contract with the reference number CEEC/04567/ CBIOS/2020. Authors also acknowledge COFAC/ILIND – Cooperativa De Formação e Animação Cultural CRL/Instituto Lusófono de Investigação e Desenvolvimento (grant COFAC/ILIND/CBIOS/2/2021). iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Fundação para a Ciência e Tecnologia (FCT) / Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged (UIDB/04462/2020 and UIDP/04462/2020). CNS acknowledge the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 804229. JAB gratefully acknowledges FCT-Fundação para a Ciência e a Tecnologia, I.P. through MOSTMICRO-ITQB R&D Unit-UIDB/04612/2020 and LS4FUTURE Associated Laboratory-LA/P/0087/2020, and by the framework of Article 23 of Decree-Law No.57/2017 of August 29. Publisher Copyright: Copyright © 2022 Raimundo, Ferreira, Pobre, Lopes-da-Silva, Brito, dos Santos, Saraiva, dos Santos and Menezes.Introduction: Diabetes is one of the major metabolic diseases worldwide. Despite being a complex systemic pathology, the aggregation and deposition of Islet Amyloid Polypeptide (IAPP), or amylin, is a recognized histopathological marker of the disease. Although IAPP proteotoxicity represents an important trigger of β-cell dysfunction and ultimately death, its exploitation as a therapeutic tool remains underdeveloped. The bioactivity of (poly)phenols towards inhibition of pathological protein aggregation is well known, however, most of the identified molecules have limited bioavailability. Methods: Using a strategy combining in silico, cell-free and cell studies, we scrutinized a unique in-house collection of (poly)phenol metabolites predicted to appear in the human circulation after (poly)phenols ingestion. Results: We identified urolithin B as a potent inhibitor of IAPP aggregation and a powerful modulator of cell homeostasis pathways. Urolithin B was shown to affect IAPP aggregation pattern, delaying the formation of amyloid fibrils and altering their size and morphology. The molecular mechanisms underlying urolithin B-mediated protection include protein clearance pathways, mitochondrial function, and cell cycle ultimately rescuing IAPP-mediated cell dysfunction and death. Discussion: In brief, our study uncovered urolithin B as a novel small molecule targeting IAPP pathological aggregation with potential to be exploited as a therapeutic tool for mitigating cellular dysfunction in diabetes. Resulting from the colonic metabolism of dietary ellagic acid in the human body, urolithin B bioactivity has the potential to be explored in nutritional, nutraceutical, and pharmacological perspectives.publishersversionpublishe

A importância do combate e prevenção da obesidade infantil: uma revisão de literatura / The importance of combat and prevention of childhood obesity: a literature review

Os dados sobre a obesidade infantil são alarmantes. É estimado pela Organização Mundial de Saúde (OMS) que, até 2025, o número de crianças obesas no planeta será em torno dos 75 milhões. Registros do Instituto Brasileiro de Geografia e Estatística (IBGE) mostram que uma em cada três crianças de 5 a 9 anos no país tem sobrepeso. É de grande importância que seja feita a análise do estado nutricional para verificar as condições de saúde dos indivíduos. A cada dia, a população brasileira passa por um rápido e complexo processo de transição nutricional, onde se evidencia o constante aumento de peso levando as pessoas ao sobrepeso. Segundo a OMS, a obesidade é identificada como um dos principais problemas de saúde pública do século, devido ao seu alcance mundial. Este estudo tem por objetivo identificar quais estratégias de prevenção da obesidade infantil são descritas na literatura dos últimos 11 anos. O presente estudo trata-se de uma revisão narrativa da literatura sobre o combate e a prevenção da obesidade infantil. O estudo foi desenvolvido seguindo algumas etapas de buscas. As intervenções dos 11 estudos analisados variam, e discorrem sobre as ações de políticas públicas; auxílio profissional para avaliar as curvas de crescimento e o estado nutricional da criança; a criação de programas de saúde; promoção da alimentação saudável nas escolas; regulamentação das propagandas de alimentos; aconselhamento e acesso à informação por parte dos pais e responsáveis; formação dos profissionais de saúde; acesso a recursos para atividade física; educação alimentar e nutricional; melhora da qualidade das aulas de educação física; entrevista motivacional; projetos comunitários; e a compreensão das variáveis de influência familiar nos estilos de vida das crianças. De acordo com a análise desses artigos, observa-se que já existem diversas estratégias para o combate e a prevenção da obesidade infantil; sendo imprescindível traçá-las de forma eficaz para o sucesso dos métodos escolhidos

Acute Auditory Stimulation with Different Styles of Music Influences Cardiac Autonomic Regulation in Men

Background: No clear evidence is available in the literature regarding the acute effect of different styles of music on cardiac autonomic control. Objectives: The present study aimed to evaluate the acute effects of classical baroque and heavy metal musical auditory stimulation on Heart Rate Variability (HRV) in healthy men. Patients and Methods: In this study, HRV was analyzed regarding time (SDNN, RMSSD, NN50, and pNN50) and frequency domain (LF, HF, and LF / HF) in 12 healthy men. HRV was recorded at seated rest for 10 minutes. Subsequently, the participants were exposed to classical baroque or heavy metal music for five minutes through an earphone at seated rest. After exposure to the first song, they remained at rest for five minutes and they were again exposed to classical baroque or heavy metal music. The music sequence was random for each individual. Standard statistical methods were used for calculation of means and standard deviations. Besides, ANOVA and Friedman test were used for parametric and non-parametric distributions, respectively. Results: While listening to heavy metal music, SDNN was reduced compared to the baseline (P = 0.023). In addition, the LF index (ms2 and nu) was reduced during exposure to both heavy metal and classical baroque musical auditory stimulation compared to the control condition (P = 0.010 and P = 0.048, respectively). However, the HF index (ms2) was reduced only during auditory stimulation with music heavy metal (P = 0.01). The LF/HF ratio on the other hand decreased during auditory stimulation with classical baroque music (P = 0.019). Conclusions: Acute auditory stimulation with the selected heavy metal musical auditory stimulation decreased the sympathetic and parasympathetic modulation on the heart, while exposure to a selected classical baroque music reduced sympathetic regulation on the heart

Roteiro para a "Acreditação" de serviços de atendimento à criança em unidades sanitárias

An evaluation model in order to judge the adequacy of services that give attention to children in public health centers at the local level is presented by the authors. The study was based essentially on and follows the same style preconized by the Discipline of Maternal Health of the S. Paulo University School of Public Health. For each of the seven parameters (physycal plan, material resources, human resources, functioning, programming and coordination with other services, programmes and institutions, personnel training and internal prophylactical activities) sets of items are presented as requisites for mark-gaining. The method is proposed as useful for the detection of deficiencies and the planning of improvements in the area of child care at the local level.É apresentado um roteiro para se aplicar o processo da "Acreditação" nos serviços de atendimento à criança em unidades sanitárias. O método, preconizado pela Disciplina Higiene Materna da Faculdade de Saúde Pública da Universidade de São Paulo, prevê normalização de pré-requisitos básicos essenciais para a boa implementação de programas da área no âmbito de atuação de unidades sanitárias

Relation between web-blight disease and common bean yield

O relacionamento entre murcha da teia micélica (Thanatephorus cucumeris Frank.) do feijoeiro comum (Phaseolus vulgaris L.) e produção de grãos foi estudado em condições de Trópico Úmido na região da Transamazônica. Utilizaram-se os dados obtidos de 24 diferentes epidemias reguladas com aplicações de fungicidas, em condições de campo. Foram testados três métodos para relacionar severidade de doença com rendimento: 1. método de ponto crítico; 2. método de pontos múltiplos; e 3. área sob curva de progresso de doença. Não houve correlação entre severidade de doença no estádio vegetativo e produção de grãos. A fase de enchimento de vagens foi identificada como ponto crítico para relacionar severidade de doença com produção de grãos da cultivar Rico 23. Os resultados demonstraram que para a determinação de perda em produção de grãos de feijoeiro, causada por murcha da teia micélica, o modelo de ponto crítico é mais adequado.The disease-yield relationship was studied in web-blight (Thanatephorus cucumeris Frank.) of common beans (Phaseolus vulgaris L.) under humid tropic conditions of Transamazon region. Data obtained from 24 different epidemics regulated by the application of fungicidal sprays were utilized. Three methods were tested for relating disease severities to grain yield: 1. critical-point method, 2. multiple-point method, 3. area under disease progress curve. There was no correlation between disease severities at vegetative growth stage and yield. Pod-filling stage was identified as critical for relating disease to grain yield in the cultivar Rico-23. The results further demonstrated that the loss in yield could be determined with reasonable accuracy utilizing the critical-point model

Chemical constituents from three medicinal plants: Piper renitens, Siparuna guianensis and Alternanthera brasiliana

Chemical study of three medicinal plants: from leaves of Piper renitens (Miq.) Yunck, Piperaceae, and Siparuna guianensis Aubl., Siparunaceae, and from flowers of Alternanthera brasiliana (L.) Kuntze, Amaranthaceae, resulted in isolation of nine compounds: three steroids, β-sitosterol, stigmasterol from P. renitens and sitosterol-3-O-β-D-glucopyranoside from A. brasiliana, the diterpene kaurane ent-kauran-16α,17-diol from P. renitens, two derivatives kaempferol-methylether, kumatakenine (kaempferol-3,7-dimethylether) and kaempferol-3,7,3'-trimethylether from S. guianensis and three flavones, crysoeriol (5,7,4'-trihydroxy-3'-methoxyflavone), tricin (5,7,4'-trihydroxy-3',5'-dimethoxyflavone) and 7-O-β-D-glucopyranoside-5,4'-dihydroxy-3'-methoxyflavone from A. brasiliana. Compounds structures were determinate using 1D and 2D ¹H NMR and 13C spectral data, mass and IR spectra, comparing with literature data

Measuring Adherence to Inhaled Control Medication in Patients with Asthma: Comparison Among an Asthma App, Patient Self‐Report and Physician Assessment

Background: Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. Methods: This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0-100). Results: A total of 193 patients (72% female; median [P25-P75] age 28 [19-41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0-71]%; 1 month: 18 [0-48]%) than patient self-report (80 [60-95]) and physician assessment (82 [51-94]) (p 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). Conclusions: Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.info:eu-repo/semantics/publishedVersio

Measuring adherence to inhaled control medication in patients with asthma: Comparison among an asthma app, patient self‐report and physician assessment

Background Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. Methods This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0–100). Results A total of 193 patients (72% female; median [P25–P75] age 28 [19–41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0–71]%; 1 month: 18 [0–48]%) than patient self-report (80 [60–95]) and physician assessment (82 [51–94]) (p 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). Conclusions Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.info:eu-repo/semantics/publishedVersio