Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.

Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2-/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory disease in WT mice. The immune response profile was characterized by an increase in the production of inflammatory mediators, such as IL-6, TNF, and CCL2. Higher levels of CCL2 at the local and systemic levels were followed by the significant recruitment of CCR2+ macrophages and a cellular response orchestrated by these cells. CCR2-/- mice showed an increase in CXCL-1 levels, followed by a replacement of the macrophage inflammatory infiltrate by neutrophils. Additionally, the absence of the CCR2 receptor protected mice from bone loss induced by MAYV. Accordingly, the silencing of CCL2 chemokine expression in vivo and the pharmacological blockade of CCR2 promoted a partial improvement in disease. Cell culture data support the mechanism underlying the bone pathology of MAYV, in which MAYV infection promotes a pro-osteoclastogenic microenvironment mediated by CCL2, IL-6, and TNF, which induces the migration and differentiation of osteoclast precursor cells. Overall, these data contribute to the understanding of the pathophysiology of MAYV infection and the identification future of specific therapeutic targets in MAYV-induced disease.IMPORTANCEThis work demonstrates the role of the CCL2/CCR2 axis in MAYV-induced disease. The infection of wild-type (WT) C57BL/6J and CCR2-/- mice was associated with high levels of CCL2, an important chemoattractant involved in the recruitment of macrophages, the main precursor of osteoclasts. In the absence of the CCR2 receptor, there is a mitigation of macrophage migration to the target organs of infection and protection of these mice against bone loss induced by MAYV infection. Much evidence has shown that host immune response factors contribute significantly to the tissue damage associated with alphavirus infections. Thus, this work highlights molecular and cellular targets involved in the pathogenesis of arthritis triggered by MAYV and identifies novel therapeutic possibilities directed to the host inflammatory response unleashed by MAYV.

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial.

In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. BACKGROUND: Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. METHODS: In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. RESULTS: In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. INTERPRETATION: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.

"Fala-M@no-COVID-19": technological development of a health navigation program for men during the pandemic.

OBJECTIVE: to develop a care-educational technology similar to a health navigation program for men during the COVID-19 pandemic. METHODS: a methodological and qualitative study of a care-educational technology of health navigation program, structured by Program Development Cycle, with 16 patient navigators and 10 professional navigators. It used reflective thematic content analysis and an adaptation model for data processing. RESULTS: the "Fala-M@ano-COVID-19"; navigation program was developed by: I) Observation of reality, problem mapping, needs assessment: content selection, creation of domains and questions; II) Theoretical-conceptual and methodological definition, creation of product under the elaboration of care plans, based on theory, process and taxonomies by a flowchart of operationalization of actions; and III) Self-assessment: qualitative research with professional navigators. FINAL CONSIDERATIONS: the technology developed, with theoretical and methodological support, allowed to derive a viable navigation program compatible with reality based on the audience's needs.

Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV).

BACKGROUND: Uncertainty over the therapeutic benefit of parenteral remdesivir in coronavirus disease 2019 (COVID-19) has resulted in varying treatment guidelines. METHODS: In a multicenter open-label, controlled, adaptive, pharmacometric platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to 1 of 8 treatment arms including intravenous remdesivir (200 mg followed by 100 mg daily for 5 days) or no study drug. The primary outcome was the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance (estimated under a linear model fit to the daily log10 viral densities, days 0-7) in standardized duplicate oropharyngeal swab eluates, in a modified intention-to-treat population. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). RESULTS: The 2 study arms enrolled 131 patients (remdesivir n = 67, no study drug n = 64) and estimated viral clearance rates from a median of 18 swab samples per patient (a total of 2356 quantitative polymerase chain reactions). Under the linear model, compared with the contemporaneous control arm (no study drug), remdesivir accelerated mean estimated viral clearance by 42% (95% credible interval, 18%-73%). CONCLUSIONS: Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Pharmacometric assessment of therapeutics using the method described can determine in vivo clinical antiviral efficacy rapidly and efficiently.

Dynamics of Early Establishment of SARS-CoV-2 VOC Omicron Lineages in Minas Gerais, Brazil.

Brazil is one of the nations most affected by Coronavirus disease 2019 (COVID-19). The introduction and establishment of new virus variants can be related to an increase in cases and fatalities. The emergence of Omicron, the most modified SARS-CoV-2 variant, caused alarm for the public health of Brazil. In this study, we examined the effects of the Omicron introduction in Minas Gerais (MG), the second-most populous state of Brazil. A total of 430 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples from November 2021 to June 2022 from Belo Horizonte (BH) city were sequenced. These newly sequenced genomes comprise 72% of all previously available SARS-CoV-2 genomes for the city. Evolutionary analysis of novel viral genomes reveals that a great diversity of Omicron sublineages have circulated in BH, a pattern in-keeping with observations across Brazil more generally. Bayesian phylogeographic reconstructions indicate that this diversity is a product of a large number of international and national importations. As observed previously, São Paulo state is shown as a significant hub for viral spread throughout the country, contributing to around 70% of all viral Omicron introductions detected in MG.

Tumour necrosis factor plays a deleterious role in the pathogenesis of chikungunya virus infection.

Arthralgia is a hallmark of chikungunya virus (CHIKV) infection and can be very debilitating and associated with a robust local inflammatory response. Many pathophysiological aspects associated with the disease remain to be elucidated. Here, we describe a novel model of CHIKV infection in immunocompetent mice and evaluate the role of tumour necrosis factor in the pathogenesis of the disease. C57BL/6 wild type (WT) or TNF receptor 1 deficient (TNFR1-/- ) mice were inoculated with 1 × 106 PFU of CHIKV in the paw. Alternatively, etanercept was used to inhibit TNF in infected WT mice. Hypernociception, inflammatory and virological analysis were performed. Inoculation of CHIKV into WT mice induced persistent hypernociception. There was significant viral replication in target organs and local production of inflammatory mediators in early time-points after infection. CHIKV infection was associated with specific humoral IgM and IgG responses. In TNFR1-/- mice, there was a decrease in the hypernociception threshold, which was associated with a milder local inflammatory response in the paw but delayed viral clearance. Local or systemic treatment with etanercept reduced CHIKV-induced hypernociception. This is the first study to describe hypernociception, a clinical correlation of arthralgia, in immunocompetent mice infected with CHIKV. It also demonstrates the dual role of TNF in contributing to viral clearance but driving tissue damage and hypernociception. Inhibition of TNF may have therapeutic benefits but its role in viral clearance suggests that viral levels must be monitored in CHIKV-infected patients and that TNF inhibitors should ideally be used in combination with anti-viral drugs.

"Fala-M@no-COVID-19": technological development of a health navigation program for men during the pandemic / "Fala-M@no-COVID-19": desarrollo tecnológico de un programa de navegación sanitaria para hombres en la pandemia / "Fala-M@no-COVID-19": desenvolvimento tecnológico de um programa de navegação em saúde para homens na pandemia

ABSTRACT Objective: to develop a care-educational technology similar to a health navigation program for men during the COVID-19 pandemic. Methods: a methodological and qualitative study of a care-educational technology of health navigation program, structured by Program Development Cycle, with 16 patient navigators and 10 professional navigators. It used reflective thematic content analysis and an adaptation model for data processing. Results: the "Fala-M@ano-COVID-19"; navigation program was developed by: I) Observation of reality, problem mapping, needs assessment: content selection, creation of domains and questions; II) Theoretical-conceptual and methodological definition, creation of product under the elaboration of care plans, based on theory, process and taxonomies by a flowchart of operationalization of actions; and III) Self-assessment: qualitative research with professional navigators. Final considerations: the technology developed, with theoretical and methodological support, allowed to derive a viable navigation program compatible with reality based on the audience's needs.

RESUMEN Objetivo: desarrollar una tecnología cuidado-educativa similar a un programa de navegación en salud para hombres durante la pandemia de COVID-19. Métodos: estudio metodológico y cualitativo de una tecnología asistencial-educativa como un programa de navegación en salud, estructurado por el Ciclo de Desarrollo del Programa, con 16 navegandos y 10 navegadores. Se utilizó el análisis de contenido temático reflexivo y un modelo de adaptación para el procesamiento de datos. Resultados: el programa de navegación "Fala-M@ano-COVID-19"; fue desarrollado por: I) Observación de la realidad, mapeo de problemas, evaluación de necesidades: selección de contenidos, creación de dominios y preguntas; II) Definición teórico-conceptual y metodológica, creación del producto bajo la elaboración de planes de cuidados, fundamentados en teoría, proceso y taxonomías mediante un diagrama de flujo de operacionalización de acciones; y III) Autoevaluación: investigación cualitativa con navegadores. Consideraciones finales: la tecnología desarrollada, con sustento teórico y metodológico, permitió derivar un programa de navegación viable compatible con la realidad a partir de las necesidades del público.

RESUMO Objetivo: desenvolver uma tecnologia cuidativo-educacional do tipo programa de navegação em saúde para homens na pandemia de COVID-19. Métodos: estudo metodológico e qualitativo de uma tecnologia cuidativo-educacional do tipo programa de navegação em saúde, estruturado pelo Program Development Cycle, com 16 navegandos e 10 navegadores. Usou análise de conteúdo temática reflexiva e modelo de adaptação para tratamento dos dados. Resultados: o programa de navegação "Fala-M@ano-COVID-19" foi desenvolvido por: I) Observação da realidade, mapeamento do problema, levantamento das necessidades: seleção de conteúdo, criação de domínios e perguntas; II) Definição teórico-conceitual e metodológica, criação do produto sob elaboração de planos de cuidados, pautados em teoria, processo e taxonomias por um fluxograma de operacionalização das ações; e III) Autoavaliação: pesquisa qualitativa com os navegadores. Considerações finais: a tecnologia desenvolvida, com suporte teórico e metodológico, permitiu derivar um programa de navegação viável e compatível à realidade com base nas necessidades do público.

Aplicabilidade da Teoria dos Sintomas Desagradáveis para a população de homens idosos com COVID-19 no Brasil / Aplicabilidad de la teoría de los sintomas desagradables a la población de hombres ancianos con COVID-19 en Brasil / Applicability of the Theory of Unpleasant Symptoms to the population of older men with COVID-19 in Brazil

Resumo Objetivo analisar os clusters de sintomas desagradáveis em homens idosos na pandemia/sindemia da COVID-19. Método estudo qualitativo, multicêntrico, realizado entre março de 2021 e abril de 2022, no qual participaram 94 homens idosos, os quais responderam a um formulário on-line. Os dados foram processados e codificados com apoio do software NVIVO, analisados por meio da técnica de Discurso do Sujeito Coletivo, e interpretados com base na Teoria dos Sintomas Desagradáveis. Resultados participaram homens entre 60 e 88 anos, de maioria autodeclarada heterossexuais e brancos. Durante os primeiros dois anos da pandemia da COVID-19, emergiram clusters de sintomas desagradáveis biopsicossociais na saúde de homens idosos como: picos de pressão alta, depressão, ansiedade e sedentarismo. O cenário pandêmico e o isolamento social foram considerados fatores influenciáveis situacionais para as diferentes dimensões dos sintomas. Como desempenho para a experiência de vivenciar os sintomas, foram considerados as consultas médicas remotas pela Telemedicina, interações afetivas virtuais e consumo de pornografia em sites eróticos. Conclusões e implicações para a prática a exposição sindêmica à COVID-19 deflagrou clusters de sintomas desagradáveis, de caráter biopsicossocial, na saúde de homens idosos brasileiros, o que requer gerenciamento pela Enfermagem.

Resumen Objetivo analizar los clusters de síntomas desagradables en hombres ancianos en la pandemia/sindemia por COVID-19. Método estudio cualitativo, multicéntrico, llevado a cabo entre marzo de 2021 y abril de 2022, han participado 94 hombres ancianos, que respondieron un formulario en línea. Los datos han sido procesados y codificados con el apoyo del software NVIVO, analizados por la técnica del Discurso del Sujeto Colectivo y la interpretación de los resultado embasada bajo la Teoría de los Síntomas Desagradables. Resultados han participado hombres entre 60 y 88 años, en su mayoría autodeclarados heterosexuales y blancos. Durante los dos primeros años de la pandemia de COVID-19, surgieron clusters de síntomas biopsicosociales desagradables en la salud de los hombres mayores, a ejemplo de: picos en la presión arterial alta; depresión; ansiedad y sedentarismo. El escenario de la pandemia y el aislamiento social fueron considerados influenciadores situacionales para las diferentes dimensiones de los síntomas y, como performance para la experiencia de vivenciar los sintomas se consideraron las consultas médicas remotas por la Telemedicina, interacciones afectivas virtuales y consumo de pornografía en sitios web eróticos. Conclusiones e implicaciones para la práctica la exposición sindémica a la COVID-19 desencadenó conglomerados de síntomas desagradables, de naturaleza biopsicosocial, en la salud de ancianos brasileños, que requieren manejo por parte de la Enfermería.

Abstract Objective To analyze clusters of unpleasant symptoms in older men with the COVID-19 pandemic/syndemic. Method A qualitative, multicenter study was carried out between March 2021 and April 2022, in which 94 older men who answered an online form participated. The data were processed and coded with the support of the NVIVO software, analyzed by the Collective Subject Discourse technique, and applied the Theory of Unpleasant Symptoms to interpret results. Results Men between 60 and 88 participated; most self-declared heterosexual and white. The pandemic scenario and social isolation were considered situational influencing factors for different dimensions of symptoms and, as a performance for the experience of living the symptoms, remote medical consultations by Telemedicine, virtual affective interactions, and consumption of pornography on erotic websites. Conclusions and implications for practice Syndemic exposure to COVID-19 triggered clusters of unpleasant symptoms, of a biopsychosocial nature, in the health of elderly Brazilian men, which requires management by Nursing.

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection.

Chikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution. Annexin A1 (AnxA1) is involved in both initiating inflammation and preventing over-response, being essential for a balanced end of inflammation. In this study, we investigated the role of the AnxA1-FPR2/ALX pathway during CHIKV infection. Genetic deletion of AnxA1 or its receptor enhanced inflammatory responses driven by CHIKV. These knockout mice showed increased neutrophil accumulation and augmented tissue damage at the site of infection compared with control mice. Conversely, treatment of wild-type animals with the AnxA1 mimetic peptide (Ac2-26) reduced neutrophil accumulation, decreased local concentration of inflammatory mediators and diminished mechanical hypernociception and paw edema induced by CHIKV-infection. Alterations in viral load were mild both in genetic deletion or with treatment. Combined, our data suggest that the AnxA1-FPR2/ALX pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia.

Disparities in Stroke Patient-Reported Outcomes Measurement Between Healthcare Systems in Brazil.

Introduction: Acute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil. Methods: PROMs through the International Consortium for Health Outcomes Measures (ICHOM) were assessed at 90 days after the stroke to compare two Brazilian hospitals in southern Brazil: a public university and a private stroke center, both with stroke protocols and stroke units. Results: When compared with the private setting (n = 165), patients from the public hospital (n = 175) were younger, had poorer control of risk factors, had more frequent previous strokes, and arrived with more severe strokes. Both hospitals had a similar percentage of IV thrombolysis treatment. Only 5 patients received mechanical thrombectomy (MT), all in the private hospital. Public hospital patients presented significantly worse outcomes at 3 months, including worse quality of life and functional dependence (60 vs. 48%, p = 0.03). Poor outcome, as measured by the mRS score, was significantly associated with older age, higher NIHSS score, and the presence of heart failure. However, the public practice was a strong predictor of any self-reported disability. Conclusion: Patients assisted at a good quality public stroke center with the same protocol used in the private hospital presented worse disability as measured by mRS and patient-reported outcome measures, with greater inability to communicate, dress, toilet, feed, and walk.

The impact Of high-intensity interval training On functioning And health-related quality Of life In post-stroke patients: A systematic review With meta-analysis.

OBJECTIVE: To examine the effects of high-intensity interval training on the functioning and health-related quality of life of post-stroke patients. METHODS: We searched the following electronic databases: MEDLINE/Pubmed, Cochrane Central Register of Controlled Trials, PEDro database, and Scielo up to January 2022 for randomized controlled trials that investigated the effects of high-intensity interval training in post-stroke patients. Two reviewers selected the studies independently. Study quality was evaluated using the PEDro scale. The mean difference (MD), standard mean difference (SMD), and 95% confidence intervals (CIs) were calculated. RESULTS: Nine studies met the study criteria (375 patients). The age of the participants ranged from 55.8 to 72.1 years. The studies included patients within 2 weeks of stroke onset to patients longer than 1 month of stroke. High-intensity interval training resulted in improvement in cardiorespiratory fitness (peak oxygen uptake) MD (3.8 mL/kg/min, 95% CI: 2.62, 5.01, n = 91), balance MD 5.7 (95% CI: 3.50, 7.91; N = 64), and gait speed SMD (0.2 m/s; 95% CI: 0.05, 0.27; N = 100) compared with continuous aerobic training. The health-related quality of life did not differ between the groups. Compared to usual care, high-intensity interval training improved the cardiorespiratory fitness SMD (0.5 95% CI: 0.14, 0.81, n = 239). No serious adverse events were observed. CONCLUSIONS: The findings of this systematic review show that high-intensity interval training was more efficient than continuous aerobic training to gain cardiorespiratory fitness, balance and gait speed in post-stroke patients. In addition, compared to usual care, high-intensity interval training improved cardiorespiratory fitness.

Efeito da distribuição da carga interna de treinamento no desempenho de salto vertical em uma pré-temporada de jogadores de voleibol de elite / Effect of the distribution of the internal load of training in vertical jump performance in a preseason of elite volleyball players

O objetivo deste estudo foi examinar os efeitos da distribuição da carga interna de treinamento no desempenho de salto vertical durante a pré-temporada em jogadores de voleibol. A amostra foi composta por 11 jogadores de voleibol da Superliga Masculina de Voleibol (26,4±5,7 anos; 96,6±9,0 kg; 197,6±7,8 cm; 8,1±2,8% de gordura). A pré-temporada foi composta por 11 semanas de treinamento, dividida em três etapas: Etapa 1, com duração de 6 semanas; Etapa 2, com duração de 3 semanas; Etapa 3, com duração de 2 semanas. A carga interna de treinamento foi avaliada em todas sessões de treinamento através da percepção subjetiva de esforço da sessão, as percepções subjetivas de fadiga foram avaliadas ao final de cada semana, por meio da escala de bem-estar e o salto vertical com contra movimento foi avaliado ao final de cada etapa. Os resultados mostraram maiores valores de carga interna de treinamento em Etapa 1 em comparação a Etapa 2 (p = 0,02) e Etapa 3 (p = 0,01), alterações no estado de bem-estar dos atletas durante as três etapas analisadas, considerando os indicadores fadiga (F = 13,1; p < 0,001), estresse (F = 23,8; p < 0,001), humor (F = 16,7; p < 0,001) e bem-estar total (F = 11,2; p < 0,001) e também alterações significativas no salto vertical com contra movimento nos diferentes momentos de avaliação (F = 7,2; p < 0,01). Conclui-se que a distribuição de carga interna de treinamento, juntamente com as capacidades físicas trabalhadas, contribui para que ocorresse melhoria do desempenho no salto vertical com contra movimento e também redução da percepção de fadiga ao final da pré-temporada. (AU)

The aim of this study was to examine the effects of internal training load distribution on vertical jump performance during preseason in volleyball players. The sample consisted of 11 volleyball players from a Men's Volleyball Superliga (26.4 ± 5.7 years, 96.6 ± 9.0 kg, 197.6 ± 7.8 cm, 8.1 ± 2.8% of fat). The pre-season consisted of 11 weeks of training, divided into three stages: Stage 1, lasting 6 weeks; Stage 2, lasting 3 weeks; Stage 3, lasting 2 weeks. The internal training load was evaluated in all training sessions through the session of rating perception of exertion, the subjective perceptions of fatigue were evaluated at the end of each week, through the well-being scale and the vertical jump with counter movement was evaluated at the end of each stage. The results showed higher internal training load values in Stage 1 compared to Stage 2 (p = 0.02) and Stage 3 (p = 0.01), changes in the athletes' state of well-being during the three stages analyzed, considering the fatigue indicators (F = 13.1; p < 0.001), stress (F = 23.8; p < 0.001), mood (F = 16.7; p < 0.001) and total well-being (F = 11.2; p < 0.001) and also significant changes in vertical jump with counter movement at different moments of assessment (F = 7.2; p < 0.01). It is concluded that the distribution of internal training load contributes to an improvement in performance in the vertical jump with counter movement and also a reduction in the perception of fatigue at the end of the pre-season. (AU)

Seroprevalence, Prevalence, and Genomic Surveillance: Monitoring the Initial Phases of the SARS-CoV-2 Pandemic in Betim, Brazil.

The COVID-19 pandemic has created an unprecedented need for epidemiological monitoring using diverse strategies. We conducted a project combining prevalence, seroprevalence, and genomic surveillance approaches to describe the initial pandemic stages in Betim City, Brazil. We collected 3239 subjects in a population-based age-, sex- and neighborhood-stratified, household, prospective; cross-sectional study divided into three surveys 21 days apart sampling the same geographical area. In the first survey, overall prevalence (participants positive in serological or molecular tests) reached 0.46% (90% CI 0.12-0.80%), followed by 2.69% (90% CI 1.88-3.49%) in the second survey and 6.67% (90% CI 5.42-7.92%) in the third. The underreporting reached 11, 19.6, and 20.4 times in each survey. We observed increased odds to test positive in females compared to males (OR 1.88 95% CI 1.25-2.82), while the single best predictor for positivity was ageusia/anosmia (OR 8.12, 95% CI 4.72-13.98). Thirty-five SARS-CoV-2 genomes were sequenced, of which 18 were classified as lineage B.1.1.28, while 17 were B.1.1.33. Multiple independent viral introductions were observed. Integration of multiple epidemiological strategies was able to adequately describe COVID-19 dispersion in the city. Presented results have helped local government authorities to guide pandemic management.

Quedas em idosos comunitários atendidos por uma estratégia de saúde da família do município de São Leopoldo: prevalência e fatores associados / Falls in community dwelling elderly assisted by a family health strategy in the municipality of São Leopoldo: prevalence and associated factors

Idosos ocupam espaço significativo em nossa sociedade gerando uma modificação na estrutura de gastos em diversas áreas. Um dos fatores que mais colaboram para gastos em saúde é a queda acidental/recorrente, evento responsável por altas taxas de mortalidade e desenvolvimento de morbidades na terceira idade. Objetivo: Identificar a prevalência de quedas em idosos e realizar um rastreio epidemiológico dos fatores de risco encontrados nesta faixa etária. Método: Trata-se de estudo observacional do tipo descritivo transversal realizado com idosos pertencentes a uma Estratégia de Saúde da Família de São Leopoldo/RS, entre fevereiro e março de 2020. A coleta de dados se deu através de cinco instrumentos: questionário de histórico de quedas; Timed Up & Go (TUG); Teste de Alcance Funcional (TAF); Dinamometria de Preensão Palmar (DPP); e Mini Exame do Estado Mental (MEEM). Para análise de dados, utilizou-se teste QuiQuadrado de Pearson, resíduos ajustados e Odds Ratio. Resultados: Amostra foi composta por 125 idosos comunitários, 66,4% do sexo feminino e com média de idade de 70,39±6,56 anos. Mais da metade sofreu queda no último ano, sendo as de tipo recorrentes as mais prevalentes (61,6%) e 53,4% destes fraturaram algum osso como resultado da queda. O histórico de quedas demonstrou associação positiva (p<0,05) ao sexo feminino, faixa etária mais elevada, viuvez, viver sozinho, polimedicação, medo de cair, ao TAF e à DPP. Conclusão: Idosos comunitários apresentam alta prevalência de quedas e diversos fatores causais associados. Reconhece-se a importância de uma avaliação multidimensional para rastrear os riscos e identificar idosos mais suscetíveis.

Elderly are a significant portion of our society, causing a change in expenses in many fields. One of the factors that collaborate the most for health expenses is the accidental/recurrent fall, responsible event for high mortality rate and the development of morbidity in the third age. Objective: Identify the prevalence of falls in elderly and make an epidemiologic tracing of the risk factors present in that age group. Method: This is an observational and cross-sectional descriptive study carried with elderly people of ESF of São Leopoldo/RS, in the period between February and March of 2020. The data collection was held by five instruments: questionnaire about falls history; Timed Up & Go (TUG); Functional Reach Teste (FRT); Handgrip Dinamometry (HGD); and Mini-Mental State Examination (MMSE). For the data analysis, the Qui-Square test, adjusted residual and Odds Ratio was used. Results: The sample consisted of 125 community elderly, 66,4% of the female sex and at the average age of 70,39±6,56 years old. More than half of them have felt in the last year, being the ones of recurrent kind the most prevalent (61,6%) and 53,4% had broken a bone because of it. The history of falls demonstrated positive association (p<0,05) to the female sex, higher group age, widowhood, living alone, polypharmacy, fear of falling, to the FRT and HGD. Conclusion: Community elderly present a high prevalence rate of falls and various causes of it. It is important to recognize the importance of a multidimensional assessment to trace the risks and to identify the more susceptible seniors to falling.

Análise do rastreamento oportuno da sífilis no pré-natal de baixo risco / Analysis of timely syphilis screening in low-risc prenatal

Este estudo teve como objetivo analisar a oferta oportuna do rastreamento da sífilis durante a gestação, no primeiro e terceiro trimestre. Trata-se de um estudo de abordagem quantitativa, transversal e descritivo, realizado com base em 41 registros de gestantes acompanhadas no Prénatal de baixo risco da Unidade Básica de Saúde União, entre junho de 2016 e junho de 2017. Observou-se que os enfermeiros solicitaram mais frequentemente o Teste Rápido - TR em 65,9% e o exame de VDRL em 46,3%, no primeiro trimestre, enquanto no terceiro trimestre os médicos solicitaram o TR em 26,8% e VDRL em 63,4%. Os TR apresentaram-se reagentes em 4,88% no primeiro trimestre, enquanto o VDRL apresentou-se regente em 2,44% neste mesmo período e, em 4,88% no terceiro trimestre.Constataram-se fragilidades no acompanhamento gestacional e oferta não oportuna do rastreamento, indicando a necessidade de investimento em estratégias de promoção e educação em saúde para combater o problema.

This study aimed to analyze the timely deployment of syphilis screening during pregnancy, both in the first and third trimesters. This is a quantitative, cross-sectional and descriptive study based on 41 records of pregnant women monitored in low-risk prenatal care at UBS (Primary Health Care Unit) União, between June 2016 and June 2017. We observed that nurses have requested the Rapid Test - RT more frequently, at 65.9%, and the VDRL test at 46.3%, in the first trimester, while in the third trimester physicians have requested the RT in 26.8% of the cases and VDRL in 63.4%. RTs were 4.88% reagent in the first trimester, while VDRL was 2.44% reagent in the same period and 4.88% in the third trimester. We found a few vulnerabilities concerning pregnancy follow-ups and the untimely deployment of screenings, indicating the need for investments in health promotion and awareness strategies in order to address this issue.

Pilates diminui exaustão e modifica ativação muscular de jogadores juvenis de futebol / Pilates reduces exhaustion and changes muscle activation in juvenile soccer players

O objetivo foi verificar se o Pilates promove mudanças na ativação muscular do membro inferior e melhorias em relação à exaustão e ao desempenho funcional dos jogadores. Participaram 15 jogadores, divididos em Grupo Pilates (GP, n=7) e Grupo Controle (GC, n=8). O GP realizou 15 sessões por cinco semanas. Avaliaram-se a exaustão e a ativação muscular [Reto Femoral (RF), Bíceps Femoral (BF), Glúteo Máximo (GM) e Reto do Abdome (RA)] durante o side hop test antes e após a intervenção. O GP sobre a exaustão mostrou diferença significativa entre pré e pós-intervenção (comparado ao próprio GP) com a eletromiografia (EMG) (p=0,01) e sem a EMG (p=0,01); em relação à ativação muscular, houve diminuição para todos os músculos, exceto para o GC. O Pilates é capaz de diminuir a exaustão e modificar a ativação muscular para possível aprendizagem motora; e quanto ao desempenho funcional não houve melhora significativa.

The objective was to verify whether Pilates promotes changes in muscle activation of the lower limb and improvements in relation to exhaustion and functional performance of soccer players. Participants were 15 players divided into Pilates Group (GP, n = 7) and Control Group (GC, n = 8). The GP held 15 sessions over five weeks. Exhaustion and muscle activation [rectus femoris (RF), biceps femoris (BF), gluteus maximus (GM) and rectus abdominis (RA)] were evaluated during the side hop test before and after intervention. The GP on exhaustion showed a significant difference between pre- and post-intervention (compared to GP itself) with electromyography (EMG) (p = 0.01) and without EMG (p = 0.01). In relation to muscle activation, there was a decrease for all muscles, except for GC. Pilates is able to reduce exhaustion and changes muscle activation for possible motor learning; and as for functional performance, there was no significant improvement.

In-depth characterization of a novel live-attenuated Mayaro virus vaccine candidate using an immunocompetent mouse model of Mayaro disease.

Mayaro virus (MAYV) is endemic in South American countries where it is responsible for sporadic outbreaks of acute febrile illness. The hallmark of MAYV infection is a highly debilitating and chronic arthralgia. Although MAYV emergence is a potential threat, there are no specific therapies or licensed vaccine. In this study, we developed a murine model of MAYV infection that emulates many of the most relevant clinical features of the infection in humans and tested a live-attenuated MAYV vaccine candidate (MAYV/IRES). Intraplantar inoculation of a WT strain of MAYV into immunocompetent mice induced persistent hypernociception, transient viral replication in target organs, systemic production of inflammatory cytokines, chemokines and specific humoral IgM and IgG responses. Inoculation of MAYV/IRES in BALB/c mice induced strong specific cellular and humoral responses. Moreover, MAYV/IRES vaccination of immunocompetent and interferon receptor-defective mice resulted in protection from disease induced by the virulent wt MAYV strain. Thus, this study describes a novel model of MAYV infection in immunocompetent mice and highlights the potential role of a live-attenuated MAYV vaccine candidate in host's protection from disease induced by a virulent MAYV strain.

Pluripotency of Wolbachia against Arboviruses: the case of yellow fever.

Background: Yellow fever outbreaks have re-emerged in Brazil during 2016-18, with mortality rates up to 30%. Although urban transmission has not been reported since 1942, the risk of re-urbanization of yellow fever is significant, as Aedes aegypti is present in most tropical and sub-tropical cities in the World and still remains the main vector of urban YFV. Although the YFV vaccine is safe and effective, it does not always reach populations at greatest risk of infection and there is an acknowledged global shortage of vaccine supply. The introgression of Wolbachia bacteria into Ae. aegypti mosquito populations is being trialed in several countries ( www.worldmosquito.org) as a biocontrol method against dengue, Zika and chikungunya. Here, we studied the ability of Wolbachia to reduce the transmission potential of Ae. aegypti mosquitoes for Yellow fever virus (YFV). Methods: Two recently isolated YFV (primate and human) were used to challenge field-derived wild-type and Wolbachia-infected ( wMel +) Ae. aegypti mosquitoes. The YFV infection status was followed for 7, 14 and 21 days post-oral feeding (dpf). The YFV transmission potential of mosquitoes was evaluated via nano-injection of saliva into uninfected mosquitoes or by inoculation in mice. Results: We found that Wolbachia was able to significantly reduce the prevalence of mosquitoes with YFV infected heads and thoraces for both viral isolates. Furthermore, analyses of mosquito saliva, through indirect injection into naïve mosquitoes or via interferon-deficient mouse model, indicated Wolbachia was associated with profound reduction in the YFV transmission potential of mosquitoes (14dpf). Conclusions: Our results suggest that Wolbachia introgression could be used as a complementary strategy for prevention of urban yellow fever transmission, along with the human vaccination program.

PER3 variable number tandem repeat (VNTR) polymorphism modulates the circadian variation of the descending pain modulatory system in healthy subjects.

We evaluated the circadian pattern of variation of the descending pain modulatory system (DPMS) using a conditioned pain modulation (CPM) paradigm according to the variable-number tandem-repeat (VNTR) of the clock gene PER3 polymorphism. We assessed the relationship between the genotypes PER34/4 and PER35/5 and the temporal pattern of variation across the day using the following measures: the heat pain threshold (HPT), the cold pressure test (CPT), and the serum levels of BDNF and S100-B protein. The ∆-values (from afternoon to morning) of these measures were used for the analysis. The circadian phenotype was according to the mid-point sleep time established by the Munich ChronoType Questionnaire (MCTQ). We included 18 healthy volunteers (15 women) ages 18 to 30. A Generalized Linear Model (GLM) revealed a significant difference in the ∆-CPM-task between Per34/4 and Per35/5 genotypes, with means (SDs) of -0.41 (0.78) vs. 0.67 (0.90) (χ2 = 7.256; df = 1' P = 0.007), respectively. Both sleep deprivation of at least 2 h/day (B = -0.96, 95% confidence interval (CI) = -1.86 to -0.11)) and the ∆-S100-B protein (-0.03, 95% CI = -0.06 to -0.02) were negatively correlated with the ∆-CPM-task, while the ∆-BDNF was positively correlated with the ∆-CPM-task (0.015, 95% CI = 0.01 to 0.03). We observed a difference in the ∆-CPT between PER34/4 and PER35/5 (0.11 (4.51) vs. 4.00 (2.60), respectively) (χ2 = 22.251; df = 1 P = 0.001). These findings suggest that the polymorphism of PER35/5 is associated with a decrease in the inhibitory function of the DPMS over the course of the day. However, sleep deprivation is an independent factor that also reduces the inhibitory function of the DPMS, regardless of the PER3 VNTR polymorphism.

Animal model of arthritis and myositis induced by the Mayaro virus.

BACKGROUND: The Mayaro virus (MAYV) is an endemic arbovirus in South American countries, where it is responsible for sporadic outbreaks of Mayaro fever. Clinical manifestations include fever, headache, ocular pain, rash, myalgia, and debilitating and persistent polyarthralgia. Understanding the mechanisms associated with MAYV-induced arthritis is of great importance due to the potential for its emergence, urbanization and dispersion to other regions. METHODS: 15-day old Balb/c mice were infected by two distinct pathways, below the forelimb and in the rear footpad. Animals were observed for a period of 21 days. During this time, they were monitored every 24 hours for disease signs, such as weight loss and muscle weakness. Histological damage in the muscles and joints was evaluated 3, 7, 10, 15 and 20 days post-infection. The cytokine profile in serum and muscles during MAYV infection was evaluated by flow cytometry at different post-infection times. For pain analysis, the animals were submitted to the von Frey test and titre in different organs was evaluated throughout the study to obtain viral kinetics. FINDINGS: Infection by two distinct pathways, below the forelimb and in the rear footpad, resulted in a homogeneous viral spread and the development of acute disease in animals. Clinical signs were observed such as ruffled fur, hunched posture, eye irritation and slight gait alteration. In the physical test, both groups presented loss of resistance, which was associated with histopathological damage, including myositis, arthritis, tenosynovitis and periostitis. The immune response was characterized by a strong inflammatory response mediated by the cytokines TNF-α, IL-6 and INF-γ and chemokine MCP-1, followed by the action of IL-10 and IL-4 cytokines. INTERPRETATION: The results showed that Balb/c mice represent a promising model to study mechanisms involved in MAYV pathogenesis and for future antiviral testing.