Diabetes Mellitus tipo 3 e exercício físico: relações entre obesidade, resistência insulínica e distúrbios cognitivos

Introdução e objetivo: O Diabetes Mellitus tipo 3 (DM3) é um termo recentemente proposto para se referir à relação entre obesidade, resistência insulínica, diabetes mellitus tipo 2 e distúrbios cognitivos. O estudo apresenta evidências acerca do DM3, e mostra o papel do exercício físico como tratamento não farmacológico para o DM3. Materiais eMétodos: Foi realizada uma revisão de artigos publicados entre 2000  e 2016 nas bases de dados MEDLINE e LILACS. Todas as etapas do processo de revisão foram realizadas por dois pesquisadores independentes. Resultados e discussão: Verificou-se a relação de distúrbios neurológicos e cognitivos com alterações cardiometabólicas; resistência à insulina e o processo inflamatório presente na obesidade. O exercício físico (EF) teve efeitos benéficos em diversos fatores de risco para o DM3. O termo DM3 salienta a influência de condições como obesidade, resistência à insulina e diabetes mellitus tipo 2 no desenvolvimento da doença de Alzheimer. Conclusão: O EF mostrou ser uma importante estratégia de prevenção/tratamento do DM3. São necessários mais estudos sobre as modalidades de EF visando consolidar conhecimentos para a elaboração de diretrizes na prescrição do EF no contexto do DM3. ABSTRACT Type 3 diabetes and physical exercise: intercourses on obesity, insulin resistance and cognitive disordersIntroduction and objective: Type 3 Diabetes Mellitus (DM3) is a term recently proposed to refer to the relationship between obesity, insulin resistance, type 2 diabetes mellitus and cognitive disorders. The study presents evidences about the DM3 and shows the role of physical exercise as a non-pharmacological treatment for DM3. Materials and Methods: It was performed a review of papers published between 2000 and 2016 from MEDLINE and LILACS databases. All stages of the review process have been conducted in two independent researchers. Results and discussion: It was observed the relationship between neurological and cognitive disorders with cardiometabolic alterations, insulin resistance and obesity related inflammatory process. Physical exercise (PE) showed beneficial effects on several risk factors for DM3. The term DM3 emphasizes the influence of conditions such as obesity, insulin resistance and type 2 diabetes mellitus on the Alzheimer's disease development. Conclusion: The PE has shown to be an important prevention/treatment strategy. Further studies are needed in PE modalities to consolidate the knowledge in the development of guidelines for PE prescription in the context of DM3

Obesity of normal weight and abdominal obesity in physical exercise practitioners: "fake lean"?

ABSTRACT Obesity of normal weight and abdominal obesity in physical exercise practitioners: "fake lean"?Introduction: Although body mass index (BMI) eutrophy is desirable for decreasing cardiovascular and metabolic risk, recent research has attributed high risk in BMI eutrophic subjects, but with a high percentage of body fat (normal weight obesity) and abdominal obesity. Aim: to analyze the prevalence of normal weight obesity (NWO) and abdominal obesity (AO) in BMI eutrophic. Materials and methods: 204 volunteers (52.26 ± 14.18 years), 168 women (52.02 ± 14.27 years) and 36 men (53.39 ± 13.90) physical exercise practitioners underwent the following procedures divided in 3 phases: 1) all sample were initially submitted to BMI, percentage of body fat (%BF) and waist-height ratio (WHR) measurements; 2) only the BMI eutrophic subjects (n=83) were evaluated separately to identify the NWO and AO prevalence; 3) In the BMI eutrophic subjects, men and women over 61 and 55 years old, respectively, were excluded, and NWO and AO were repeated in the remaining subjects (n=52). Results: In the general sample, %BF was lower in men than women (18.61 ± 6.05 vs. 28.78 ± 5.24). For age, WHR and BMI, the statistical analysis showed no significant difference. In the BMI eutrophic subjects (N=83), 14.9% of the women presented NWO, representing 13.3% of the total. No man presented NWO. In this same sample, 44.4% of the men and 24.3% of the women had WHR over the optimal, representing 26.5% of the eutrophic subjects. Excluding the eutrophic subjects over 61 (men) and 55 years old (women) (N=52), 14.9% of the women presented NWO, representing 13.5% of the total. Conclusion: In BMI eutrophic subjects, 13 and 26% of the subjects presented NWO and AO, respectively. NWO was observed exclusively in women, whereas AO was more present in men.Introdução: Embora a eutrofia no índice de massa corporal (IMC) seja desejável para diminuição do risco cardiometabólico, pesquisas recentes têm atribuído risco elevado em sujeitos eutróficos no IMC, porém como elevado percentual de gordura corporal (%GC) (obesidade do peso normal) e obesidade abdominal (OA). Objetivo: analisar a prevalência de obesidade do peso normal (OPN) e OA em sujeitos eutróficos no IMC. Materiais e métodos: 204 voluntários (52,26 ± 14,18 anos), sendo 168 mulheres (52,02 ± 14,27 anos) e 36 homens (53,39 ± 13,90) praticantes de exercício físico participaram do estudo, que foi realizado em 3 fases: 1) toda amostra foi inicialmente submetida às avaliações de IMC, %GC e relação cintura-estatura (RCE); 2) somente os sujeitos eutróficos no IMC (n=83) foram avaliados separadamente para identificação da prevalência de OPN e OA; 3) dos sujeitos eutróficos, foram excluídos homens e mulheres com idade acima de 61 e 55 anos, respectivamente, e repetidas as análises de OPN e OA nos sujeitos restantes (n=52). Resultados: Na amostra geral, o %GC foi menor nos homens em relação às mulheres (18,61 ± 6,05 vs. 28,78 ± 5,24). Para idade, RCE e IMC, a análise estatística não revelou diferença significativa entre sexos. Nos sujeitos eutróficos (n=83), 14,9% das mulheres apresentaram OPN, representando 13,3% do total. Nenhum homem apresentou esse quadro. Nesse mesmo recorte amostral, 44,4% dos homens e 24,3% das mulheres apresentaram RCE acima do ideal, representando 26,5% dos eutróficos. Excluindo-se os sujeitos eutróficos acima de 61 (homens) e 55 anos (mulheres) (n=52), 14,9% das mulheres apresentaram OPN, representando 13,5% do total. Conclusão: Em sujeitos eutróficos no IMC, 13 e 26% da amostra apresentaram OPN e OA, respectivamente. A OPN foi observada exclusivamente em mulheres, enquanto a OA foi mais presente em homens.Univ Fed Sao Paulo, Lab Interdisciplinar Doencas Metabol, Grp Estudos Obesidade, Santos, SP, BrazilFac Praia Grande, Fac Educ Fis, Praia Grande, SP, BrazilPrefeitura Municipal Santos, Secretaria Esportes, Secao Avaliacao Fis, Santos, SP, BrazilUniv Santa Cecilia, Fac Educ Fis & Esportes, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Biociencias, Santos, SP, BrazilUniv Fed Sao Paulo, Lab Interdisciplinar Doencas Metabol, Grp Estudos Obesidade, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Biociencias, Santos, SP, BrazilWeb of Scienc

The human carotid atherosclerotic plaque: an observational review of histological scoring systems

OBJECTIVE: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS: A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events

Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-α 2b treatment

<p>Abstract</p> <p>Background</p> <p>High-dose interferon-alpha 2b (IFN-α 2b) is the only approved systemic therapy in the United States for the adjuvant treatment of melanoma. The study objective was to explore the immunomodulatory mechanism of action for IFN-α 2b by measuring serum regulatory T cell (Treg), serum transforming growth factor-β (TGF-β), interleukin (IL)-10, and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-α 2b regimen.</p> <p>Methods</p> <p>Patients with melanoma received IFN-α 2b administered intravenously (20 MU/m²each day from day 1 to day 5 for 4 consecutive weeks). Serum Treg levels were measured as whole lymphocytes in CD4⁺cells using flow cytometry while TGF-β, IL-10, and autoantibody levels were measured using enzyme-linked immunosorbent assays.</p> <p>Results</p> <p>Twenty-two patients with melanoma received IFN-α 2b treatment and were evaluated for Treg levels. Before treatment, Treg levels were significantly higher in patients with melanoma when compared with data from 20 healthy subjects (<it>P </it>= 0.001; Mann-Whitney test). Although a trend for reduction of Treg levels following IFN-α 2b treatment was observed (average decrease 0.29% per week), statistical significance was not achieved. Subgroup analyses indicated higher baseline Treg levels for stage III versus IV disease (<it>P </it>= 0.082), early recurrence versus no recurrence (<it>P </it>= 0.017), deceased versus surviving patients (<it>P = </it>0.021), and preoperative neoadjuvant versus postoperative adjuvant treatment groups (not significant). No significant effects were observed on the levels of TGF-β, IL-10, and autoantibodies in patients with melanoma treated with IFN-α 2b.</p> <p>Conclusions</p> <p>Patients with melanoma in this study showed increased basal levels of Treg that may be relevant to their disease and its progression. Treg levels shifted in patients with melanoma treated with IFN-α 2b, although no firm conclusions regarding the role of Tregs as a marker of treatment response or outcome can be made at present.</p

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic

Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Planning and managing a seismic emergency: The INGV drill of November 26th, 2015 carried out in the framework of the activity line T5 "Seismic surveillance and post-earthquake operational procedures" | Pianificazione e gestione di un'emergenza sismica: Esercitazione INGV del 26 novembre 2015 effettuata nell'ambito della Linea di Attività T5 "Sorveglianza sismica e operatività post terremoto"

Nella Struttura Terremoti dell’INGV la Linea di Attività T5 “Sorveglianza sismica ed operatività postterremoto” si occupa delle attività di sviluppo di strumenti e procedure per la valutazione in tempo reale degli effetti di terremoti e tsunami e della gestione delle emergenze sismiche. Uno dei suoi obiettivi del 2015 era la formalizzazione dei protocolli di intervento di Gruppi d’Emergenza, avvenuta per Emergeo, Emersito, IES, QUEST e Sismiko con Decreto del Presidente nel luglio 2015. Altro obiettivo era l’elaborazione di un Protocollo di Ente per la gestione delle emergenze sismiche. La bozza preparata nel 2015 prevede l’importante novità dell’Unità di Crisi, mai formalizzata in precedenza. Attraverso questo Protocollo di Ente si auspica di migliorare la risposta logistico-operativa dell’INGV durante l’emergenza, di avere una più rapida conoscenza del fenomeno in corso e di realizzare un’efficace comunicazione verso Protezione Civile, media e pubblico. Per verificare il tutto è stata organizzata un’esercitazione in cui è stato simulato un terremoto di magnitudo 6.4 nel basso Lazio. Si sono così sperimentate l’efficacia del flusso azioni/informazioni durante un’emergenza, il funzionamento dell’Unità di Crisi, la funzionalità dei protocolli dei Gruppi d’Emergenza, l’efficienza delle attività in sede per gli aspetti tecnico-logistici, il flusso di comunicazione interno e le comunicazioni istituzionali esterne (queste ultime simulate). In questo articolo sono descritte le fasi di organizzazione ed attuazione dell’esercitazione. Inoltre, durante il suo svolgimento, la valutazione dell’efficacia dell’organizzazione e delle attività svolte dai gruppi coinvolti è stata affidata ad alcuni osservatori e qui è allegata l’elaborazione dei commenti riportati. Abbiamo fatto infine una sintesi dei risultati positivi e delle criticità emerse dall’esercitazione, attività così importante a nostro avviso da considerarne indispensabile la ripetizione con cadenza quanto meno annuale.Published1SR. TERREMOTI - Servizi e ricerca per la SocietàN/A or not JCRope

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

JUNO Sensitivity to Invisible Decay Modes of Neutrons

We explore the bound neutrons decay into invisible particles (e.g., $n\rightarrow 3 \nu$ or $nn \rightarrow 2 \nu$) in the JUNO liquid scintillator detector. The invisible decay includes two decay modes: $n \rightarrow { inv}$ and $nn \rightarrow { inv}$. The invisible decays of $s$-shell neutrons in $^{12}{\rm C}$ will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $\bar{\nu}_e$, natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $\tau/B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, {\rm yr}$ and $\tau/B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, {\rm yr}$.Comment: 28 pages, 7 figures, 4 table