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Zusammenfassung Zu Beginn des Beitrages werden verschiedene Lokalisierungstechniken auf Basis von Ultraschall für einzelne und mehrere mobile Objekte (Sensoren) in einem zylindrischen Behälter verglichen. Eine Untergliederung erfolgt im Bezug zu der Fähigkeit des Sensors, aktiv Signale und/ oder Daten für die Ortung zu senden und einer passiven Lokalisierung. Weiterhin erfolgt eine Gegenüberstellung der möglichen maximalen Energieausbeute, der für den Anwendungsfall ausgewählten Methode. Zur Validierung der Funktionsprinzipien erfolgen experimentelle Untersuchungen an einem Messaufbau mit Wassertank. Erforderliche Komponenten zur Signalgenerierung sowie Datenerfassung werden aufgezeigt und diskutiert. Des weiteren wird die Energieausbeute in Bezug zur Einsatzdauer eines ausgewählten Mikrocontrollers dargelegt.

Differences between the sexes among the non-elderly with heart failure (HF) have been insufficiently evaluated. This study aims to investigate sex-related differences in early-onset HF.Patients aged 18 to 54 years who were registered from 2003 to 2014 in the Swedish Heart Failure Register were included. Each patient was matched with two controls from the Swedish Total Population Register. Data on comorbidities and outcomes were obtained through the National Patient Register and Cause of Death Register.We identified 3752 patients and 7425 controls. Of the patients, 971 (25.9%) were women and 2781 (74.1%) were men with a mean (standard deviation) age of 44.9 (8.4) and 46.4 (7.3) years, respectively. Men had more hypertension and ischemic heart disease, whereas women had more congenital heart disease and obesity. During the median follow-up of 4.87 years, 26.5 and 24.7 per 1000 person-years male and female patients died, compared with 3.61 and 2.01 per 1000 person-years male and female controls, respectively. The adjusted hazard ratios for all-cause mortality, compared with controls, were 4.77 (3.78-6.01) in men and 7.84 (4.85-12.7) in women (p for sex difference = 0.11). When HF was diagnosed at 30, 35, 40, and 45 years, women and men lost up to 24.6 and 24.2, 24.4 and 20.9, 20.5 and 18.3, and 20.7 and 16.5 years of life, respectively.Long-term mortality was similar between the sexes. Women lost more years of life than men.

Some studies suggest that resource-rich countries tend to allocate talent and investment toward the resource sector and away from manufacturing or agriculture reducing the competitiveness of these other sectors. Because mining overwhelmingly employs men, when other sectors shrink so do employment opportunities for women (Ross, 2008). This could significantly affect core social structures. Using plausibly exogenous variation in natural resource wealth due to giant oil discoveries and an event study design, this paper finds that giant oil discoveries are associated with relatively worse female outcomes as measured by higher male/female population ratios, higher teen birth rates, and lower educational attendance of tertiary education among women relative to men. However, the impact on health outcomes tapers off within 8 years. Additionally, during periods of increasing oil prices, there is no significant evidence of such effects possibly due to an income effect.

Introduction: Centralized management of queues helps to reduce the surgical waiting time in the publicly funded healthcare system, but this is not a reality in the Brazilian Unified Healthcare System. Objectives: To describe the implementation of the “Patients with Surgical Indication” (PSI) in a Brazilian public tertiary hospital; To assess the impact on waiting time and its use in rationing oncological surgeries during the COVID-19 Pandemic. Methods: Retrospective observational study of elective surgical requests (2016-2022) in a Brazilian general, public, tertiary university hospital. We recovered information regarding the inflows (indications), outflows and their reasons, the number of patients, and waiting time in queue. Results: We enrolled 82,844 indications in the PSI (2016-2022). The waiting time (median and interquartile range) in days decreased from 98(48;168) in 2016 to 14(3;152) in 2022 (pConclusion: Implementing a centralized list of surgical indications and developing queue management principles proved feasible, with effective rationing. It unprecedentedly demonstrated the decrease in the median waiting time in Brazil.

Aims Factors influencing follow-up referral decisions and their prognostic implications are poorly investigated in patients with heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction (EF). We assessed (i) the proportion of, (ii) independent predictors of, and (iii) outcomes associated with follow-up in specialty vs. primary care across the EF spectrum. Methods and results We analysed 75 518 patients from the large and nationwide Swedish HF registry between 2000-2018. Multivariable logistic regression models were fitted to identify the independent predictors of planned follow-up in specialty vs. primary care, and multivariable Cox models to assess the association between follow-up type and outcomes. In this nationwide registry, 48 115 (64%) patients were planned for follow-up in specialty and 27 403 (36%) in primary care. The median age was 76 [interquartile range (IQR) 67-83] years and 27 546 (36.5%) patients were female. Key independent predictors of planned follow-up in specialty care included optimized HF care, that is follow-up in a nurse-led HF clinic [odds ratio (OR) 4.60, 95% confidence interval (95% CI) 4.41-4.79], use of HF devices (OR 3.99, 95% CI 3.62-4.40), beta-blockers (OR 1.39, 95% CI 1.32-1.47), renin-angiotensin system/angiotensin-receptor-neprilysin inhibitors (OR 1.21, 95% CI 1.15-1.27), and mineralocorticoid receptor antagonists (OR 1.31, 95% CI 1.26-1.37); and more severe HF, that is higher NT-proBNP (OR 1.13, 95% CI 1.06-1.20) and NYHA class (OR 1.13, 95% CI 1.08-1.19). Factors associated with lower likelihood of follow-up in specialty care included older age (OR 0.29, 95% CI 0.28-0.30), female sex (OR 0.89, 95% CI 0.86-0.93), lower income (OR 0.79, 95% CI 0.76-0.82) and educational level (OR 0.77, 95% CI 0.73-0.81), higher EF [HFmrEF (OR 0.65, 95% CI 0.62-0.68) and HFpEF (OR 0.56, 95% CI 0.53-0.58) vs. HFrEF], and higher comorbidity burden, such as presence of kidney disease (OR 0.91, 95% CI 0.87-0.95), atrial fibrillation (OR 0.85, 95% CI 0.81-0.89), and diabetes mellitus (OR 0.92, 95% CI 0.88-0.96). A planned follow-up in specialty care was independently associated with lower risk of all-cause [hazard ratio (HR) 0.78, 95% CI 0.76-0.80] and cardiovascular death (HR 0.76, 95% CI 0.73-0.78) across the EF spectrum, but not of HF hospitalization (HR 1.06, 95% CI 1.03-1.10). Conclusions In a large nationwide HF population, referral to specialty care was linked with male sex, younger age, lower EF, lower comorbidity burden, better socioeconomic environment and optimized HF care, and associated with better survival across the EF spectrum. Our findings highlight the need for greater and more equal access to HF specialty care and improved quality of primary care. Funding Agencies|Boston ScientificBoston Scientific; EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart [116074]

SummaryEfficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg. Remarkably, unsupervised clustering analysis of pre-treatment T cell subsets revealed differences in individuals that went on to respond to PD-1 blockade compared to individuals that did not. These differences mapped to expression of the proliferation marker Ki67 and the costimulatory receptor CD28 as well as the inhibitory molecules 2B4 and KLRG1. While these results require validation in larger patient cohorts, they suggest that flow cytometric analysis of a relatively small number of T cell markers in peripheral blood could potentially allow stratification of PD-1 blockade treatment response prior to therapy initiation.

Heterozygous mutations inCTLA-4result in an inborn error of immunity with an autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications of allogeneic hematopoietic stem cell transplantation. Here, we designed a homology-directed repair (HDR) gene editing strategy that inserts theCTLA-4cDNA into the first intron of theCTLA-4genomic locus in primary human T cells. This resulted in regulated expression of CTLA-4 in CD4+T cells, and functional studies demonstrated CD80 and CD86 transendocytosis. Gene editing of T cells isolated from three patients with CTLA-4 insufficiency also restored CTLA-4 protein expression and rescued transendocytosis of CD80 and CD86 in vitro. Last, gene-corrected T cells fromCTLA-4−/−mice engrafted and prevented lymphoproliferation in an in vivo murine model of CTLA-4 insufficiency. These results demonstrate the feasibility of a therapeutic approach using T cell gene therapy for CTLA-4 insufficiency.

Summary Curbing unwanted T cell responses by costimulation blockade has been a recognised immunosuppressive strategy for the last 15 years. However, our understanding of how best to deploy this intervention is still evolving. A key challenge has been the heterogeneity in the clinical response to costimulation blockade, and an inability to predict which individuals are likely to benefit most. Here, we discuss our recent findings based on the use of costimulation blockade in people with type 1 diabetes (T1D) and place them in the context of the current literature. We discuss how profiling follicular helper T cells (Tfh) in pre-treatment blood samples may have value in predicting which individuals are likely to benefit from costimulation blockade drugs such as abatacept.

The relevance of the problem of therapy and prevention of SARS-CoV-2 is associated with the development of pulmonary edema, the lack of rehabilitation methods and accurate diagnostic indicators of pulmonary edema. In this regard, the objective of this work was to evaluate the level of free sialic acids and the therapeutic effect of EHF therapy in rats with pulmonary edema. The work was carried out on 14 sexually mature female Wistar rats weighing 150-200g, divided into 3 groups. An EHF therapy biocorrector (CEM-TECH, 40–43 GHz, Russia) was used for 10 days for treatment. A standard reaction method with 2-thiobarbituric acid was used for the determination of free sialic acids. In the control group, the level of free sialic acids was increased by 2 times (0.420 ± 0.011 µmol / ml). In the experimental group, EHF therapy reduced the level of free sialic acids by 1.8 times (0.235 ± 0.043 µmol / ml). The level of free sialic acids increases with the development of pulmonary edema. This result may suggest the use of this indicator in addition to the known traditional methods of diagnosis and prognosis of pulmonary edema, as well as in pulmonary rehabilitation in patients infected with SARS-CoV-2.

Wheat blast, caused by the fungus Magnaporthe oryzae Triticum (MoT) pathotype, is one of the most important yield-reducing diseases of wheat, mainly in the tropical wheat-growing regions of South America. In this study, we assessed the effects of nitrogen (N) fertilization on wheat blast epidemics. Factorial experiments were carried out in Londrina (2015 and 2016) and Floresta (two sowings in 2017) with N rates (0, 40, 80 and 120 kg/ha for the first experiment, and 0, 60 and 120 kg/ha for the second) and wheat genotypes (three and six cultivars, for the first and second experiments, respectively) as factors. Wheat blast on spikes occurred only in two out of four experiments: 2015 in Londrina and first sowing of 2017 in Floresta. Nitrogen increased blast severity in the first crop of 2017 in Floresta, where blast severity on spikes ranged from 10 to 94% and yield ranged from 47 to 2823 kg/ha, depending on N rate and genotype. Nitrogen did not affect wheat blast (except for genotype S1) in the 2015 Londrina trial, where blast severity on spikes ranged from 16.9 to 36.8%. Differences in blast severity among genotypes were likely due to different crop heading periods. Our results suggest that N fertilization and sowing time should be considered in a management strategy for reducing the risk of wheat blast epidemics.

Understanding the spatial variability of soil fertility is necessary for preventing nutrient losses or excessive agricultural inputs. The aim of this research was to evaluate the spatial variability of the chemical characteristics of a Typic Hapludox cultivated with soybean for 110 days at different depths and the impacts of these characteristics on crop yield. Soil samples were collected at a total of 80 points in an area of 5000 m2 . The contents of P, Ca, Mg, S, Cu, Fe, Zn and Mn were analyzed, in addition to pH and H+Al. The data were evaluated through descriptive statistics and geostatistical tools, and kriging maps were made based on semivariogram adjustments. Most of the soil fertility variables showed moderate or strong spatial dependence. The statistical moments obtained for the distributions showed that the symmetry of the distributions allowed the use of geostatistics techniques. In general, the greater the soil depth was, the lower the nutrient levels were. The soybean yield range (29.5 m) was similar to the P range in the 0.0-0.20 m soil layer (29.2 m). P influenced the soybean yield the most, as expressed by the similarity between the two kriging maps. In regions with more phosphorus at deeper soil layers, higher soybean yields were obtained.

Therapeutic targeting of immune checkpoints has garnered significant attention in the area of cancer immunotherapy, in which efforts have focused in particular on cytotoxic T lymphocyte antigen 4 (CTLA4) and PD1, both of which are members of the CD28 family. In autoimmunity, these same pathways can be targeted to opposite effect: to curb the over-exuberant immune response. The CTLA4 checkpoint serves as an exemplar, whereby CTLA4 activity is blocked by antibodies in cancer immunotherapy and augmented by the provision of soluble CTLA4 in autoimmunity. Here, we review the targeting of co-stimulatory molecules in autoimmune diseases, focusing in particular on agents directed at members of the CD28 or tumour necrosis factor receptor families. We present the state of the art in co-stimulatory blockade approaches, including rational combinations of immune inhibitory agents, and discuss the future opportunities and challenges in this field. Immune activating antibodies that target co-stimulatory molecules have altered the cancer therapy landscape. Here, Walker and colleagues discuss therapies — particularly those that target molecules in the same families as CTLA4 and PD1 or TNF receptor — that inhibit the immune system and are being investigated for the treatment of autoimmune diseases. They describe the future opportunities and challenges for the field, including combination approaches.

Made available in DSpace on 2020-12-12T02:25:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Background: New antithrombotic strategies that reduce primary thrombosis and restenosis might improve vascular outcomes in patients with peripheral artery disease (PAD) undergoing arterial angioplasty. The study objective is to evaluate the potential benefit of apixaban plus aspirin compared with standard of care dual antiplatelet therapy (DAPT) in reducing thrombotic restenosis and artery re-occlusion in patients undergoing endovascular infrapopliteal revascularization. Study design: This multicenter, parallel-group, prospective, randomized, open-label, blinded-endpoint adjudication, proof-of-concept, exploratory trial aims to randomize 200 patients 72 hours after successful infrapopliteal angioplasty for critical limb ischemia (CLI). Patients will be randomly assigned in a 1:1 ratio to receive oral apixaban (2.5 mg twice daily) plus aspirin (100 mg once daily) for 12 months or clopidogrel (75 mg daily) for at least 3 months on a background of aspirin (100 mg once daily) for 12 months. The primary endpoint is the composite of target lesion revascularization (TLR), major amputation, or restenosis/occlusion (RAS) in addition to major adverse cardiovascular events – MACE (myocardial infarction, stroke or cardiovascular death) at 12 months. The primary safety endpoint is the composite of major bleeding or clinically relevant non-major bleeding at 12 months. This study will evaluate the efficacy and safety of apixaban 2.5 mg twice daily plus aspirin compared with DAPT (clopidogrel plus aspirin) in patients with CLI undergoing endovascular infrapopliteal revascularization and might prove the concept of an alternative antithrombotic regimen for these patients to be tested in a future large randomized clinical trial. São Paulo State Public Servant Hospital Duke Clinical Research Institute Duke University School of Medicine Science Valley Research Institute Albert Einstein Hospital Universidade Estadual Paulista (UNESP) Santa Casa de Maceio Maceio Hospital das Clínicas de Ribeirão Preto São Paulo University Medical School (USP) Santa Casa de São Paulo School of Medical Sciences Beneficência Portuguesa de São Paulo Hospital das Clínicas de São Paulo São Paulo University Vascular and Endovascular Surgery–Federal University of Bahia Federal University of São Paulo Inova Heart and Vascular Institute Hemostasis & Thrombosis Research Laboratories at Loyola University Medical Center Universidade Estadual Paulista (UNESP)

Zusammenfassung In diesem Beitrag wird das Fokussierverhalten mittels akustischer Zeitumkehr in Wasser diskutiert. Als Grundlage zur Generierung einer hochaufgelösten örtlichen und zeitlichen Fokussierung dient eine eigenentwickelte FPGA-basierte Plattform (auf einem ZynqMP Ultrascale+). Diese ermöglicht eine synchrone Anregung von bis zu 32 Wandlern bei einer Abtastrate von 4,8 MSa/s und 8 bit Amplitudenauflösung. Zudem wird die gewählte Filter- und Verstärkertechnik vorgestellt und die FPGA-Plattform mit einem kommerziellen analogen System verglichen. Die Messung des Schalldruckfeldes innerhalb der Flüssigkeit erfolgt über ein Nadelhydrophon, das an ein 3D-Schallfeldscanner-System angekoppelt ist. Die im Kalibrierschritt der Methodik erzeugten analogen zeitumgekehrten Impulsantworten werden über eine frequenz- und auflösungsabhängige Pulsweitenmodulation (PWM) für die darauffolgende synchrone FPGA-Ansteuerung umgewandelt. Der jeweilige Fokuspunkt wird hinsichtlich seiner Amplitude, räumlichen Auslenkung sowie dem Kontrastverhältnis des Fokuspunktes gegenüber dessen akustisch nicht adressierten Umgebung bewertet. Dabei wird die Fokusqualität bezüglich einer unterschiedlichen Wandleranzahl und an verschiedenen Zielpositionen untersucht.

Follicular helper T (TFH) cells are implicated in type 1 diabetes (T1D), and their development has been linked to CD28 costimulation. We tested whether TFH cells were decreased by costimulation blockade using the CTLA-4–immunoglobulin (Ig) fusion protein (abatacept) in a mouse model of diabetes and in individuals with new-onset T1D. Unbiased bioinformatics analysis identified that inducible costimulatory molecule (ICOS)+ TFH cells and other ICOS+ populations, including peripheral helper T cells, were highly sensitive to costimulation blockade. We used pretreatment TFH profiles to derive a model that could predict clinical response to abatacept in individuals with T1D. Using two independent approaches, we demonstrated that higher frequencies of ICOS+ TFH cells at baseline were associated with a poor clinical response following abatacept administration. Therefore, TFH analysis may represent a new stratification tool, permitting the identification of individuals most likely to benefit from costimulation blockade. The CTLA-4–Ig fusion protein (abatacept) can have beneficial effects in autoimmune disease. Walker and colleagues show in mouse and human type 1 diabetes that abatacept targets pathogenic follicular helper T cells, and the frequencies of these cells at baseline can be used to stratify treatment responses in patients.

The Insomnia Severity Index (ISI) is an insomnia self-report measure used to identify individuals at risk for insomnia disorder. Although the full ISI is only seven questions, a briefer version wou...

Timely resolution of bacterial infections critically depends on phagocytosis of invading pathogens by polymorphonuclear neutrophil granulocytes (PMNs), followed by PMN apoptosis and efferocytosis. Here we report that bacterial DNA (CpG DNA) and mitochondrial DNA impair phagocytosis and attenuate phagocytosis-induced apoptosis in human PMNs through Toll-like receptor 9 (TLR9)-mediated release of neutrophil elastase and proteinase 3 and subsequent down-regulation of the complement receptor C5aR. Consistently, CpG DNA delays pulmonary clearance of Escherichia coli in mice and suppresses PMN apoptosis, efferocytosis, and generation of proresolving lipid mediators, thereby prolonging lung inflammation evoked by E. coli Genetic deletion of TLR9 renders mice unresponsive to CpG DNA. We also show that aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4) and 17-epi-resolvin D1 (17-epi-RvD1) through the receptor ALX/FPR2 antagonize cues from CpG DNA, preserve C5aR expression, restore impaired phagocytosis, and redirect human PMNs to apoptosis. Treatment of mice with 15-epi-LXA4 or 17-epi-RvD1 at the peak of inflammation accelerates clearance of bacteria, blunts PMN accumulation, and promotes PMN apoptosis and efferocytosis, thereby facilitating resolution of E. coli-evoked lung injury. Collectively, these results uncover a TLR9-mediated endogenous mechanism that impairs PMN phagocytosis and prolongs inflammation, and demonstrate both endogenous and therapeutic potential for 15-epi-LXA4 and 17-epi-RvD1 to restore impaired bacterial clearance and facilitate resolution of acute lung inflammation.

Made available in DSpace on 2020-12-10T19:54:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) BACKGROUND: The literature on physical activity practice through sports as a protective factor for back pain in adolescents is conflicting. However, few studies have aimed to verify if continuity of the practice of physical activity from childhood to adolescence may be related to lower chances of back pain in adolescents. OBJECTIVES: The objective of this study was to analyze the association between physical activity practice from childhood to adolescence and back pain in adolescents. METHODS: The random sample was composed of 870 adolescents with a mean age of 13.7 +/- 2.0 years. The continuity of physical activity practice was assessed through the continuity of sports practice from childhood to adolescence. Pain in the neck and low back were evaluated through a questionnaire. RESULTS: The prevalence of neck pain and low back pain in boys was 17.5% and in girls was 20.9% for neck pain and 21.9% for low back pain. Physical activity practice during childhood to adolescence was a protective factor for neck pain (OR = 0.57 [CI = 0.35-0.94]) and low back pain (OR = 0.53 [CI = 0.33-0.86]) in girls and neck pain in boys (OR = 0.52 [CI = 0.30-0.90]), even after adjusting for confounding factors. CONCLUSION: Girls with physical activity practice during childhood to adolescence were less likely to develop neck pain and back pain when compared to girls who did not maintain practice of physical activity. Similar results were observed in boys considering neck pain. Univ Estadual Paulista, Postgrad Program Motr Sci, Presidente Prudente, SP, Brazil Univ Fed Minas Gerais, Dept Physiotherapy, Belo Horizonte, MG, Brazil Univ Estadual Paulista, Postgrad Program Physiotherapy, Presidente Prudente, SP, Brazil Univ Estadual Paulista, Postgrad Program Motr Sci, Presidente Prudente, SP, Brazil Univ Estadual Paulista, Postgrad Program Physiotherapy, Presidente Prudente, SP, Brazil FAPESP: 2016/02258-3 CNPq: 442395/2014-0 CAPES: 001

Objective: Investigate the relationship between different domains of physical activity and resting heart rate (RHR) in boys and girls. Method: The sample included 1011 adolescents, aged between 10 and 17 years. RHR was measured by a heart rate monitor and physical activity was assessed in total and in three different domains (school, occupational, and sports practice) by a questionnaire. Anthropometry was directly obtained for body mass index and central fat. Ethnicity, sedentary behavior, and smoking habits were self-reported and used to adjust the analysis, through hierarchical linear regression. Results: Total physical activity was associated with low RHR in boys (β = −0.52; 95% CI: −0.92, −0.12) and girls (β = −0.67; 95% CI: −1.07, −0.28). Although sporting physical activities were associated with low RHR in both boys (β = −0.58; 95% CI: −1.05, −0.11) and girls (β = −0.87; 95% CI: −1.34, −0.39), occupational physical activity was related to low RHR only in boys (β = −1.56; 95% CI: −2.99, −0.14). Conclusion: The practice of physical activity in the sport practice domain and total physical activity were related to low RHR in both sexes, while occupational physical activities were associated with RHR only in boys. Resumo: Objetivo: Investigar a relação entre diferentes domínios de atividade física e frequência cardíaca de repouso (FCRep) em meninos e meninas. Método: A amostra incluiu 1.011 adolescentes, com idade entre 10 e 17 anos. A FCRep foi medida por um monitor de frequência cardíaca e a atividade física foi avaliada no total e em três diferentes domínios (escolar, ocupacional e prática esportiva) através de um questionário. A antropometria foi obtida diretamente para o índice de massa corporal e gordura central. Etnia, comportamento sedentário e tabagismo foram autorrelatados e usados para ajustar a análise, através da regressão linear hierárquica. Resultados: A atividade física total foi associada à baixa FCRep nos meninos (β = -0,52; IC95% -0,92; -0,12) e meninas (β = -0,67; IC95% -1,07; -0,28). Embora as atividades físicas esportivas estivessem associadas à baixa FCRep em ambos meninos (β = -0,58; IC95% -1,05, -0,11) e meninas (β = -0,87; IC95% -1,34, -0,39), a atividade física ocupacional estava relacionada à baixa FCRep apenas em meninos (β = -1,56; IC95% -2,99; - 0,14). Conclusão: A prática de atividade física no domínio da prática esportiva e a atividade física total foram relacionadas à baixa FCRep em ambos os sexos, enquanto as atividades físicas ocupacionais foram associadas à FCRep apenas em meninos. Keywords: Physical activity, Resting heart rate, Sedentary behavior, School, Palavras-chave: Atividade física, Frequência cardíaca de repouso, Comportamento sedentário, Escola

A child with pre-B acute lymphoblastic leukaemia (ALL) developed fatal encephalitis associated with human coronavirus OC43 (HCoV-OC43). During chemotherapy the child had a persistent HCoV-OC43 respiratory infection and later developed progressive encephalitis. Cerebrospinal fluid was negative for pathogens including HCoV-OC43, but a brain biopsy was HCoV-OC43-positive by metagenomic next-generation sequencing.

The Child Report of Posttraumatic Symptoms (CROPS) is an effective 26-item trauma assessment tool. Research has indicated a 14-item version of the CROPS for juvenile offenders with improved predictive accuracy for detecting trauma exposure among male offenders and commensurate accuracy for female offenders. However, the 14-item scale has yet to be validated for juvenile offenders with an established trauma measure. Cross-sectional retrospective data of 74 adjudicated youth (59.5% male) from the original CROPS 14-item psychometric study sample were used to examine the factor structure, internal consistency, and convergent and divergent validity of the 14-item scale. Findings indicated strong internal consistency and significant correlations with all scales of an established and more extensive trauma measure for children and adolescents. Findings also revealed a CROPS 12-item model explaining 36.9% of variance. Results supported both convergent and divergent validity, suggesting both the CROPS 14-item and 12-item may be used as valid trauma symptom screeners for juvenile offenders.

Objective: The purpose of this study was to investigate the clinical evolution of patients treated with carbon-coated stent, as well as its patency and the inflammatory response triggered by this process through the quantification of serum elements of the kallikrein-kinin system (KKS). Methods: This was a single-center prospective study with 27 patients with peripheral artery disease (PAD) who required percutaneous transluminal angioplasty and stenting of the iliacofemoropopliteal segment using carbon-coated stent grafts (carbostents). The blood concentrations of the total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein levels were assessed by the colorimetric method and tissue kallikrein levels were evaluated by the spectrophotometric method. The activity of kininase II was measured by ­fluorometric analysis. Results: Of the 27 patients who completed the 6 months of the study (11 iliac territory, 16 femoropopliteal territory), only one experienced restenosis (3.7%) (femoropopliteal segment) and no patient had occlusion (96.3% of patency). In 1 year, four patients were lost to follow-up and all 23 patients evaluated maintained stent patency, except for the patient who had restenosis throughout the first 6 months. We report complete (100%) member salvage in 12 months of follow-up. The activity levels of high- and low-molecular-weight kininogens decreased significantly over time (before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.001, and before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.001; 24 h vs. 6 months, p < 0.001, respectively). Patients also had significantly lower levels of plasma and tissue kallikrein (before vs. 24 h, p < 0.001; before vs. 6 months, p < 0.001, and before vs. 24 h, p < 0.01; before vs. 6 months, p < 0.05, respectively). There was a significant increase in the enzymatic activity of kininase II at 24 h and after 6 months compared to the pre-treatment control (p < 0.001). Conclusion: Our early experience shows that the use of carbon-coated stents in PAD appears to be safe, with low rates of early restenosis (3.7% in the first 6 months and 5% in the 12 months of follow-up). We concluded that KKS was involved in the inflammatory response caused by the placement of carbon-coated stents.

Background In-stent restenosis remains a common and important complication after endovascular treatment of superficial femoral artery peripheral artery disease. It occurs in 14 to 35% of cases in 1 year and there is still no efficient treatment for this condition. Paclitaxel-coated balloons have shown promising results. Objective Investigate the 3 year results of superficial femoral artery in-stent restenosis treated with paclitaxel-coated balloon angioplasty, using the Lutonix™ 035 device. Methods We conducted a retrospective observational study with patients with symptomatic (Rutherford 2 to 5) superficial femoral artery in-stent restenosis, that were treated with paclitaxel-coated balloon angioplasty using the Lutonix™ 035 device, in a single center from January 2016 to December 2020. Duplex scan was used to follow the patients. Primary patency was obtained through Kaplan-Meier analysis. Mortality, and amputation rates were also evaluated. Results 105 patients were included. Two patients had technical failure and required an additional stent, and were thus excluded. 103 patients were analyzed. Primary patency was 91.26, 80.47, and 67.71%, respectively, in the first, second, and third year after the procedure. There were no deaths 30 days after the procedure. There were no major amputations during the 3 year follow-up. Conclusion Paclitaxel-coated balloon angioplasty with the Lutonix™ 035 device was a safe and effective treatment to superficial femoral artery in-stent restenoses. The results were maintained along the 3 year follow-up.

Transfemoral carotid artery stenting (TF-CAS) and carotid endarterectomy (CEA) are alternative strategies for stroke prevention in patients with atherosclerotic carotid disease. Because their main objective is to prevent future ischemic events, regular reassessment of the outcomes is mandatory for providing the best therapy. The purpose of this study was to describe the practice and the outcomes of TF-CAS and CEA in symptomatic patients in public university hospitals in Brazil, using data from a prospective multicentric registry.A prospective 8-year observational study of patients with symptomatic carotid artery atherosclerotic disease that underwent TF-CAS and CEA in 5 public university hospitals affiliated with the RHEUNI (Registry Project of Vascular Disease in the Public University Hospitals of São Paulo). All consecutive procedures were included. The indications for the procedures were determined by each surgeon's individual discretion, in accordance with a preoperative risk evaluation. The outcome measures were any 30-day follow-up death, stroke, myocardial infarction (MI), and their combined outcome (major adverse cardiovascular events [MACE]). The registration of the study was made at clinicaltrials.gov NCT02538276.From January 2012 through December 2019, 376 consecutive and symptomatic patients were included in the study records. There were 152 TF-CAS procedures (40.4%) and 224 CEA procedures (59.5%). All completed the 30-day follow-up period. Occurrence of death (TF-CAS: 0.66% × CEA: 0.66%, P = 0.99), stroke (TF-CAS: 4.61% × CEA: 4.46%, P = 0.99), and MI (TF-CAS: 0.66% × CEA: 0%, P = 0.403) were similar in both groups, without statistically significant differences. MACE rate did not differ in both groups (TF-CAS: 5.92% × CEA: 4.46%, P = 0.633).Data from a prospective registry of 5 Brazilian university hospitals showed that TF-CAS and CEA in symptomatic patients had similar 30-day perioperative rates of death, stroke, and MI and their combination.

Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback of this approach is impaired regulatory T cell homeostasis that requires CD28 signaling. Therefore, strategies that restrict the effects of costimulation blockade to effector T cells would be advantageous. Here we probe the relative roles of CD28 and IL-2 in maintaining Treg. We find provision of IL-2 counteracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the conventional T cell compartment. These data suggest that combining costimulation blockade with IL-2 treatment may selectively impair effector T cell responses while maintaining regulatory T cells. Using a mouse model of autoimmune diabetes, we show combined therapy supports regulatory T cell homeostasis and protects from disease. These findings are recapitulated in humanised mice using clinically relevant reagents and provide an exemplar for rational use of a second immunotherapy to offset known limitations of the first.

A new model for the location and distribution of carbonate ions in carbonated apatite was used to assign the IR spectra of A- and AB-carbonated apatites. The percentage of total carbonate as measured by the mass loss in the TGA of these compounds is in good agreement with the percentage obtained by combustion analysis. The decomposition of pure A-type carbonate appears at temperatures of 985–1123 °C, whereas the decomposition of AB-type carbonated apatites occurs in the range of 600–800 °C. This difference is attributed to changes in the environment of channel carbonate brought about by B-type substitution of carbonate for phosphate. In the presence of sodium ions, the channel is changed by substitution of sodium for calcium in order to accommodate the difference between the charge of the carbonate and phosphate ions. A thermodynamic cycle is introduced to rationalize the differences in decomposition temperatures of A- and B-type carbonate. Preferential loss of B-type carbonate upon heating to 600 °C also suggests the migration of B-type carbonate to A-sites.

Aim: The prognostic value of natriuretic peptides in the management of heart failure (HF) patients with ejection fraction (EF) 40%, HFpEF) managed in primary care.We show that high NT-proBNP predicts increased all-cause mortality in HFpEF-patients managed in primary care.The clinical use is however limited due to large standard deviations, many co-morbidities and high age.Many of these co-morbidities contribute to all-cause mortality and management of these patients should also focus on these co-morbidities.

The Minnesota Multiphasic Personality Inventory – Adolescent (MMPI-A) is a widely researched personality assessment in psychology. However, the utility of the MMPI-A for detecting trauma am...

Evaluation and improvement of immobilization methods are important for wildlife welfare and biodiversity conservation. The sedative and physiological effects of xylazine (50-110 mg per elephant; 0.09-0.15 mg/kg IM) were evaluated in 15 juvenile Asian elephants (Elephas maximus) in Sri Lanka. The time from xylazine injection until first sign of sedation, handling, and reversal with yohimbine (0.009-0.03 mg/kg IV) were recorded. Behavioral signs, level of sedation (no effect, light, moderate, or deep) and response to handling were assessed. Rectal temperature, pulse, and respiratory rates were recorded and arterial blood samples were analyzed 30 and 45 min after xylazine injection. The first sign of sedation occurred within 5-18 min. Standing sedation was induced in all elephants, but the level of sedation varied differently over time for each elephant. Twelve elephants remained standing throughout the sedation period, while 3 elephants became laterally recumbent. Sedative effects included lowered head and trunk, droopy ears, snoring, and penis protrusion. Pulse rate, respiratory rate, and rectal temperature ranged between 30-45 beats/min, 4-12 breaths/min, and 35.6-37.2°C, respectively, at 30 min after xylazine injection, and there were no changes over time. Pulmonary function and acid-base balance were adequate (range partial pressures of arterial oxygen 73-123 mmHg and carbon dioxide 33-52 mmHg, arterial hemoglobin oxygen saturation 96-99%, pH 7.34-7.54, lactate 0.9-2.5 mmol/L). Yohimbine was administered 46-110 min after the injection of xylazine, and the first sign of recovery occurred within 1-4 min. Resedation after reversal with yohimbine was observed in two elephants. In conclusion, xylazine at the doses used induced light to deep sedation with stable physiology and most elephants remained standing.

This study explored the bacterial transmission between patients and dogs during dog-assisted therapy (DAT). Twenty children (55% girls) with a median age of 7 years (range 3-17 years) were included. Two dogs assisted and the conditions were more restricted hygienically with dog 2. Samples from child and dog were collected and cultured before and after each DAT visit. The results showed that dog 1 transmitted bacteria repeatedly to the children. No bacteria were transmitted with dog 2. In conclusion, exchange of bacteria can occur between dog and child during DAT, but it can be reduced by simple infection control measures.

Postendarterectomy carotid pseudoaneurysms are infrequent. The endovascular treatment is less invasive, with a minor risk of complications. However, the presence of a highly angulated aortic arch (type III) is a challenge, since the navigation of endovascular devices is not favorable. Through transcervical access, it is possible to deliver the devices directly into the carotid artery. We herein present a case of a postendarterectomy carotid pseudoaneurysm in a patient with type III aortic arch that was successfully treated with transcervical endograft exclusion.

Resumo A forma arterial da síndrome do desfiladeiro torácico é rara e está associada a uma anomalia anatômica, geralmente uma costela cervical. Suas manifestações são muito variadas. Este artigo tem como proposta relatar dois casos de apresentações clínicas distintas: microembolização e aneurisma. Em ambos, uma costela cervical estava presente. O diagnóstico foi realizado através da história, do exame físico, das manobras posturais e das radiografias. A angiotomografia computadorizada proporcionou o detalhe anatômico necessário para o planejamento operatório. O tratamento cirúrgico foi realizado pela abordagem supraclavicular, com sucesso em ambos casos.

Evaluation and improvement of immobilization methods are important for wildlife welfare and biodiversity conservation. The sedative and physiological effects of xylazine (50-110 mg per elephant; 0.09-0.15 mg/kg IM) were evaluated in 15 juvenile Asian elephants (

Resumo A forma arterial da síndrome do desfiladeiro torácico é rara e está associada a uma anomalia anatômica, geralmente uma costela cervical. Suas manifestações são muito variadas. Este artigo tem como proposta relatar dois casos de apresentações clínicas distintas: microembolização e aneurisma. Em ambos, uma costela cervical estava presente. O diagnóstico foi realizado através da história, do exame físico, das manobras posturais e das radiografias. A angiotomografia computadorizada proporcionou o detalhe anatômico necessário para o planejamento operatório. O tratamento cirúrgico foi realizado pela abordagem supraclavicular, com sucesso em ambos casos.

Background Arterial thoracic outlet syndrome (aTOS) is characterized by compression of the subclavian artery as it exits the thoracic girdle. Chronic and repetitive compression leads to several degrees of arterial wall damage. The treatment is varied and depends on the presentation severity. This study aimed to describe the contemporary experience in managing arterial thoracic outlet syndrome at a large tertiary hospital. Methods We conducted a single-institution retrospective review of aTOS cases from January 2009 to January 2020. Demographic data, clinical presentation, medical images, operative notes, and outcomes were assessed. Results Thirteen aTOS cases were identified. The mean age was 43 ± 10 years, and 11 (85%) were women. Both sides were equally affected: right (7 cases, 54%) and left (6 cases, 46%). The most common clinical presentation was arm claudication (7 cases, 54%). Other presentations were: acute arm ischemia, pulsatile neck mass and distal embolization. Cervical ribs were identified by plain X-rays in most cases. All patients were submitted to surgical decompression through the supraclavicular approach. Patients with early disease stages were not submitted to arterial reconstruction and were followed with duplex scan. Arterial reconstruction was done in advanced disease stages (5 cases, 38%): end-to-end anastomosis, interposition graft, and bypass graft. The mean follow-up duration was 32,6 ± 25 months. In all patients, the subclavian artery/graft was patent, and the vascular symptoms were entirely resolved. There were no deaths or amputations. Conclusions Arterial thoracic outlet syndrome has a varied clinical presentation. Cervical ribs are the most common anatomic abnormalities. The diagnosis was based on history, physical examination, and imaging exams. Surgery consisted of supraclavicular decompression, arterial resection, and vascular reconstruction, according to the disease stage. The outcomes were excellent.

Background There is a lack of data evaluating excess mortality risk (over that of the general population) and life-years lost in young patients with different heart failure (HF) phenotypes. Purpose To study excess risk for all-cause mortality in patients Methods All patients ≥18 years registered in the national quality register SwedeHF from 2003 to 2014 were included. Patients were divided into ≥55 years and Results In total 60,962 patients, out of whom 3752 50%. Patients with HF50% more often had hypertension (40.6% vs. 29.8%), hypertrophic cardiomyopathy (11.5% vs. 0.7%) and congenital heart disease (7.6% vs. 2.7%), all p>0.001. Cardiovascular death was the most common cause of death in all EF categories (about 55%). In a Cox proportional hazard model, patients with EF >50% had hazard ratio (HR) (95% CI) 10.6 (5.71–19.8), those with EF 40–49% 6.83 (4.43–10.5) and patients with EF50% lost 32.3, 28.7, 26.1, 26.3 and 21.6 “life years” as presented in figure 1. Conclusion HF patients 50% had different coexisting conditions and higher mortality risk, although not significant when compared to patients with EF 50% lost more life years than patients with EF Figure 1 Funding Acknowledgement Type of funding source: None

Therapeutic targeting of immune checkpoints has garnered significant attention in the area of cancer immunotherapy, in which efforts have focused in particular on cytotoxic T lymphocyte antigen 4 (CTLA4) and PD1, both of which are members of the CD28 family. In autoimmunity, these same pathways can be targeted to opposite effect: to curb the over-exuberant immune response. The CTLA4 checkpoint serves as an exemplar, whereby CTLA4 activity is blocked by antibodies in cancer immunotherapy and augmented by the provision of soluble CTLA4 in autoimmunity. Here, we review the targeting of co-stimulatory molecules in autoimmune diseases, focusing in particular on agents directed at members of the CD28 or tumour necrosis factor receptor families. We present the state of the art in co-stimulatory blockade approaches, including rational combinations of immune inhibitory agents, and discuss the future opportunities and challenges in this field.

Aims The prevalence and hospitalizations of patients with heart failure (HF) aged = 18 years in the Swedish Heart Failure Register from 2003 to 2014 were included. Data were merged with National Patient and Cause of Death Registers. Among 60 962 patients, 3752 (6.2%) were = 55 years, patients = 55 years, patients = 55 years. The highest mortality risk relative to that of controls was among the youngest patients. Funding Agencies|Swedish Research CouncilSwedish Research Council [2013-5187 SIMSAM]; Swedish state [ALFGBG-433211, ALFGBG-725081, ALFGBG-717211]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [2013-0307, 2018-0419, 2015-0438]; Vastra Gotaland Region; Gothenburg Society of Medicine [GLS-328971]; Swedish Council for Health, Working Life and Welfare (FORTE) [2013-0325]; Cardiology Research Foundation at the Medical Clinic at Sahlgrenska University Hospital/Ostra; Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology and Cardiology Research Foundation

Timely resolution of bacterial infections critically depends on phagocytosis of invading pathogens by polymorphonuclear neutrophil granulocytes (PMNs), followed by PMN apoptosis and efferocytosis. Here we report that bacterial DNA (CpG DNA) and mitochondrial DNA impair phagocytosis and attenuate phagocytosis-induced apoptosis in human PMNs through Toll-like receptor 9 (TLR9)-mediated release of neutrophil elastase and proteinase 3 and subsequent down-regulation of the complement receptor C5aR. Consistently, CpG DNA delays pulmonary clearance of

Resumo O aneurisma da artéria torácica interna é uma entidade rara, com apresentação variável e risco potencial de ruptura e de morte. A angiotomografia é o exame diagnóstico de escolha, sendo útil para o planejamento terapêutico. Considerando morbidade do acesso torácico para abordagem direta e o risco imprevisível de ruptura, o procedimento endovascular se apresenta como modalidade terapêutica de escolha para tratamento desse tipo de aneurisma. Descrevemos um caso de aneurisma de artéria torácica interna, com descoberta incidental na investigação de síncope tratado com embolização com micromolas de baixo perfil e de liberação controlada.

Over half a century of research substantiate that some individuals are at increased risk for perioperative neurological injury and postoperative cognitive dysfunction (POCD) following cardiac surgery. Perioperative neurovascular damage associated with cardiosurgical intervention ranges from overt stroke to covert embolic injury, while other perioperative complications confer additive or additional risks (e.g., hypoperfusion, neuroinflammation, etc.). While cardiosurgical procedures (both simple and complex) carry inherent risks for a myriad of potential neurological and systemic complications, the full panoply of causal mechanisms and their interaction producing POCD remain elusive. Noncardiac surgery has been associated with similar patterns of POCD, but several lines of research demonstrate that both early and late onset rates of POCD are considerably higher among those who underwent cardiac compared to noncardiac surgery. While cardiac surgery is associated with higher rates of POCD and neurological complications, the presence of POCD in noncardiac surgical interventions suggests that there are shared general surgical factors contributing to POCD onset and severity.

Objective: To study the characteristics and prognostic implications of type 2 diabetes in different heart failure entities from a nationwide perspective. Methods: This observational study comprised 30,696 heart failure patients prospectively included in the Swedish Heart Failure Registry (SwedeHF) 2003–2011 from specialist care, with mortality information available until December 2014. Patients were categorized into three heart failure entities by their left ventricular ejection fraction (heart failure with preserved ejection fraction: ⩾50%, heart failure with mid-range ejection fraction: 40%–49% and heart failure with reduced ejection fraction: Results: Among the patients, 22% had heart failure with preserved ejection fraction, 21% had heart failure with mid-range ejection fraction and 57% had heart failure with reduced ejection fraction. The proportion of type 2 diabetes was similar, ≈25% in each heart failure entity. Patients with type 2 diabetes and heart failure with preserved ejection fraction were older, more often female and burdened with hypertension and renal impairment compared with heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction patients among whom ischaemic heart disease was more common. Type 2 diabetes remained an independent mortality predictor across all heart failure entities after multivariable adjustment, somewhat stronger in heart failure with left ventricular ejection fraction below 50% (hazard ratio, 95% confidence interval; heart failure with preserved ejection fraction: 1.32 [1.22–1.43], heart failure with mid-range ejection fraction: 1.51 [1.39–1.65], heart failure with reduced ejection fraction: 1.46 [1.39–1.54]; p-value for interaction, p = 0.0049). Conclusion: Type 2 diabetes is an independent mortality predictor across all heart failure entities increasing mortality risk by 30%–50%. In type 2 diabetes, the heart failure with mid-range ejection fraction entity resembles heart failure with reduced ejection fraction in clinical characteristics, risk factor pattern and prognosis.

The objective of this study was to evaluate the relationship between inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), and highly sensitive C-reactive protein, and the development of arterial restenosis 6 months after femoropopliteal percutaneous transluminal angioplasty (PTA) with covered stent implantation.We recruited 27 patients of a tertiary hospital in Brazil who were treated with covered stents for atherosclerotic peripheral arterial disease. Serum samples were collected before stent implantation, then 24 hr later, and 6 months after the procedure.At 6-month follow-up, 4 patients (15%) presented restenosis. IL1- β, IL-6, IL-8, and TNF-α levels showed a statistically significant reduction after both 24 hr and 6 months compared with pretreatment levels (P 0.01). There were increased levels of IL-10 and TGF-β both 24 hr and 6 months after PTA and stenting compared with pretreatment levels (P 0.01). None of the cytokines studied were correlated with restenosis.This study demonstrated a significant increase in anti-inflammatory TGF-β and IL-10 and a decrease in proinflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α 6 months after the procedure, but no inflammatory marker was independently identified as a risk factor for in-stent restenosis.