Development and validation of a real-time PCR assay protocol for the specific detection and quantification of pelagiphages in seawater samples.

Earth is inhabited by numerous adaptations of cellular forms shaped by the persistent scrutiny of natural selection. Thus, as natural selection has fixed beneficial adaptations of functional traits, cellular life has conquered almost all environmental niches on our planet. However, cellular life succumbs in number and genetic diversity to viruses. Among all viruses, phages are highly prevalent in diverse environments, and due to their vast genetic diversity and abundance, their relevant role as significant players in several ecological processes is now fully recognized. Pelagiphages, bacteriophages infecting bacteria of the SAR11 clade, are the most abundant viruses in the oceans. However, the ecological contribution of pelagiphages on populations of Pelagibacterales remains largely underestimated. An essential aspect of estimating the impact of bacteriophages is their absolute and precise quantification, which provides relevant information about the host-virus interactions and the structure of viral assemblages. Consequently, due to its abundance and claimed influence in the biogeochemical cycling of elements, the accurate quantification of pelagiphages results in an essential task. This study describes the development and validation of a sensitive, specific, accurate and reproducible qPCR platform targeting pelagiphages. Moreover, this method allowed the detection and quantification of pelagiphages in the Gulf of California for the first time.

ß-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify ß-hydroxybutyrate (ßHB), a ketone body, as a regulator of protein solubility in the aging brain. ßHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate ßHB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-ß, and exogenous ßHB ameliorates pathology in nematode models of amyloid-ß aggregation toxicity. We have generated a comprehensive atlas of the ßHB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within ßHB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among ßHB targets and the clearance of these targets from mouse brain, likely via ßHB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.

Arena surface vertical impact forces vary with surface compaction.

Mechanical properties of arena surfaces are extrinsic factors for musculoskeletal injury. Vertical impact forces of harrowed and compacted cushion were measured at five locations on 12 arena surfaces (five dirt, seven synthetic [dirt and fiber]). Eight variables related to impact force, displacement, and acceleration were calculated. Surface temperature, cushion depth and moisture content were also measured. The effects of surface material type (dirt/synthetic) and cushion compaction (harrowed/compacted) on vertical impact properties were assessed using an analysis of variance. Relationships of manageable surface properties with vertical impact forces were examined through correlations. Compacted cushion exhibited markedly higher vertical impact force and deceleration with lower vertical displacement than harrowed cushion (P < 0.001), and the effect was greater on dirt than synthetic surfaces (P = 0.039). Vertical displacement (P = 0.021) and soil rebound (P = 0.005) were the only variables affected by surface type. Surface compaction (harrowed, compacted) had a significantly greater effect on vertical impact forces than surface type (dirt, synthetic). By reducing surface compaction through harrowing, extrinsic factors related to musculoskeletal injury risk are reduced. These benefits were more pronounced on dirt than synthetic surfaces. These results indicate that arena owners should regularly harrow surfaces, particularly dirt surfaces.

Shear ground reaction force variation among equine arena surfaces.

Shear forces at the surface-hoof interface affect hoof slide, surface grip, forces transferred to the limb, and injury risk. However, the variation in shear forces among surfaces with different compositions have not been quantified. Shear ground reaction forces were measured on five dirt and seven synthetic arena surfaces. Cohesion/adhesion and angle of internal friction/coefficient of friction were calculated. Surface composition, surface temperature, cushion depth, and moisture content were also measured. The effects of surface material (dirt/synthetic) on shear properties were assessed using analysis of variance (ANOVA; P < 0.05). The relationships between surface composition or management properties and shear properties were analyzed using linear correlation. Shear properties were not different between dirt and synthetic surface categories; however, surface fiber content was correlated with adhesion and coefficient of friction. These correlations predict that more fiber will decrease soil adhesion (r = -0.75; P < 0.01) and increase the coefficient of friction (r = 0.81; P < 0.01). Furthermore, maximum shear force was significantly correlated with cushion depth (r = 0.61; P < 0.01) and moisture content (r = 0.57; P < 0.01), where shear force was greater on surfaces with thicker cushion layers or higher moisture content. The findings suggest that shear mechanical behavior is more dependent on surface composition than surface material categories (dirt/synthetic) and also indicate that arena owners can influence shear forces by adjusting either surface composition or management.

Variation in renal parameter values after a change in antiretroviral therapy from elvitegravir/cobicistat/emtricitabine/tenofovir-alafenamide to bictegravir/emtricitabine/tenofovir-alafenamide / Variación de los valores de los parámetros renales tras un cambio en la terapia antirretroviral de elvitegravir/cobicistat/emtricitabina/tenofoviralafenamida a bictegravir/emtricitabina/ tenofovir-alafenamida

El cambio de EVG/COBI/FTC/TAF a BIC/FTC/TAF es una estrategia para optimizar la terapia antirretroviral. Nuestro objetivo fue analizar cómo variaban los parámetros analíticos renales tras cambiar tratamiento. Los objetivos secundarios fueron determinar si edad y sexo de los pacientes y el tiempo que habían tomado cobicistat previamente condicionaba la posible variación de los parámetros renales. Se realizó un estudio piloto observacional, descriptivo y ambispectivo. Los parámetros renales se obtuvieron de las analíticas previas más cercanas al cambio (considerándose este valor el basal) y después de 12, 24 semanas y 12 meses tras cambiar tratamiento. Se incluyeron 60 pacientes. En los niveles de creatinina sérica, se observó cambio a las 24 semanas (aumento medio de 0,06 mg/dL, p=0,025) y a los 12 meses (aumento medio de 0,03 mg/dL, p=0,05). Considerando la tasa de filtración glomerular (CKD-EPI), hubo bajada en los 3 períodos analizados, pero sin significación estadística. No hubo influencia del sexo, edad ni tiempo que los pacientes habían tomado cobicistat previamente. (AU)

Switching of EVG/COBI/FTC/TAF to BIC/FTC/TAF is a valid strategy for antiretroviral therapy optimization. Our aim was to analize how the variation of analytical parameters for renal function estimation after the change of their treatment. Secondary objectives were to determine if age and sex of the patients and the time they have previously taken cobicistat conditions the possible variation in renal parameters. An observational, descriptive and ambispective pilot study was performed. The renal laboratory parameters were obtained from the previous laboratory tests closest in time to the change (this value being considered the baseline) and after 12, 24 weeks and 12 months after a change in treatment with BIC/FTC/TAF. 60 patients were included. Regarding serum creatinine levels, a change in serum creatine levels was observed at 24 weeks (mean increase of 0.06 mg/dL, p=0.025) and at 12 months (mean increase of 0.03 mg/dL, p=0.05). Considering glomerular filtration (CKD-EPI), there was downward trend in the 3 periods analyzed, but statistical significance was not reached. There was no influence of sex, age and the length of time that the patients had taken cobicistat before the change. (AU)

Indicadores basados en consumo en una Unidad de Cuidados Intensivos sin implantación de PROA / Indicators based on consumption in an intensive care unit without antimicrobial stewardship programs implementation

Objetivo: Medir los indicadores del uso hospitalario de antibióticos basados en datos de consumo, comparando datos entre 2018 y 2019 en una Unidad de Medicina Intensiva de un hospital de tercer nivel sin implantación de Programas de Optimización de Antibióticos (PROA). Métodos: Asignar un valor a cada indicador evaluado en base a datos de consumo empleando los datos del programa de gestión del Servicio de Farmacia y las DDD porcada 100 estancias. En base a la diferencia de las medias obtenidas entre 2018 y 2019 se calculó la significación estadística mediante la t-Student de medidas pareadas. Resultados: Se evaluaron 13 indicadores, de los cuales sólo 2(15%) presentaron diferencias estadísticamente significativas, el consumo de fluorquinolonas y el ratio fluconazol/equinocandinas, mostrando una evolución positiva. Conclusiones: El empleo de estos indicadores deberían estandarizarse para la evaluación de las políticas antibióticas de los centros, lo que serviría para establecer comparaciones entre centros de similares características o bien la evolucióntemporal para un mismo centro y/o servicio. Esto permitiríadetectar puntos críticos y establecer acciones de mejora, entre ellas la creación de equipos PROA, especialmente en unidades de pacientes críticos. (AU)

Objective: The aim of our study is tocalculate the indicators of hospital useof antimicrobial agents based on consumption, comparing data from 2018with data from 2019 in an IntensiveCare Unit of a third level hospital without an stewardship program.Methods: Retrospective study in whichwe assigned a value to each indicatorbased on consumption using DDD per100 bed-stays. Data was obtainedusing the pharmacy management software. Statistical analysis was performed by t-Student test based on thedifference of means obtained in 2018and 2019 respectively.Results: 13 indicators were evaluated,only 2 of them (15%) showed an statistically significant difference betweenperiods, the consumption of fluoroquinolones and the fluconazole/ echinocandin ratio, both showing a positiveevolution.Conclusions: The use of these indicatorsshould be standardized in order to evaluate antibiotic policies, which will helpestablishing comparisons between centers of specific characteristics or studying the temporal evolution for thesame center and/or service. This willallow detecting critical points and establishing improvement actions, includingthe creation of stewardship programs,especially in critical care units. (AU)

Impact of BK Polyomavirus Plasma Viral Load in Kidney Transplant Outcomes.

BACKGROUND: BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival. METHODS: A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss. RESULTS: A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n = 35 and high-level viremia, n = 26). In logistic regression analysis male sex (odds ratio [OR], 4.226; 95% CI, 1.660-10.758, P = .002), age (OR, 1.047; 95% CI, 1.008-1.088; P = .018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P = .047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P = .004), and graft survival was lower in patients with BKVi and high-level viremia (P = .027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P = .029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P = .046) were predictors of shorter graft survival. CONCLUSIONS: BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.

Regulation of cardiac ion channels by transcription factors: Looking for new opportunities of druggable targets for the treatment of arrhythmias.

Cardiac electrical activity is governed by different ion channels that generate action potentials. Acquired or inherited abnormalities in the expression and/or function of ion channels usually result in electrophysiological changes that can cause cardiac arrhythmias. Transcription factors (TFs) control gene transcription by binding to specific DNA sequences adjacent to target genes. Linkage analysis, candidate-gene screening within families, and genome-wide association studies have linked rare and common genetic variants in the genes encoding TFs with genetically-determined cardiac arrhythmias. Besides its critical role in cardiac development, recent data demonstrated that they control cardiac electrical activity through the direct regulation of the expression and function of cardiac ion channels in adult hearts. This narrative review summarizes some studies showing functional data on regulation of the main human atrial and ventricular Na+, Ca2+, and K+ channels by cardiac TFs such as Pitx2c, Tbx20, Tbx5, Zfhx3, among others. The results have improved our understanding of the mechanisms regulating cardiac electrical activity and may open new avenues for therapeutic interventions in cardiac acquired or inherited arrhythmias through the identification of TFs as potential drug targets. Even though TFs have for a long time been considered as 'undruggable' targets, advances in structural biology have led to the identification of unique pockets in TFs amenable to be targeted with small-molecule drugs or peptides that are emerging as novel therapeutic drugs.

Evaluation of Expanded Criteria Donors Using the Kidney Donor Profile Index and the Preimplantation Renal Biopsy.

The increasing comorbidity of kidney transplant (KT) donors make it necessary to develop scores to correctly assess the quality of kidney grafts. This study analyzes the usefulness of the preimplantation biopsy and the Kidney Donor Profile Index (KDPI) as indicators of KT survival from expanded criteria donors (ECD). Retrospective study of KT in our center between January 2010 to June 2019 who received a kidney from an ECD and underwent a preimplantation biopsy. 266 KT were included. Graft survival was categorized by KDPI quartiles: Q1 = 86%, Q2 = 95%, Q3 = 99% and Q4 = 100%. KT from KDPI Q1 presented better survival (p = 0.003) and Q4 donors had worse renal function (p = 0.018) and poorer glomerular filtration rate (3rd month; p = 0.017, 1st year; p = 0.010). KT survival was analyzed according to KDPI quartile and preimplantation biopsy score simultaneously: Q1 donors with biopsy score ≤3 had the best survival, especially comparing against Q3 with a biopsy score >3 and Q4 donors (p = 0.014). In multivariable analysis, hyaline arteriopathy, glomerulosclerosis, and KDPI Q4 were predictors for graft survival. High KDPI and a greater histological injury in the preimplantation biopsy, especially glomerular and vascular lesions, were related to a higher rate of KT loss from ECD.

Mismatch repair system in colorectal cancer. Frequency, cancer phenotype, and follow-up.

INTRODUCTION AND AIMS: A frequent task in the study of colorectal carcinomas (CRC) is to identify tumors harboring deficient DNA mismatch repair systems (dMMR), which are associated with microsatellite instability. Given that there is scant information on those tumors in Mexican patients, our aim was to describe their frequency, clinical and pathologic characteristics, and results, which are necessary for future trials. MATERIALS AND METHODS: A consecutive series of CRC patients, treated and followed at a tertiary care center was performed. The clinical and pathologic variables and the risk of hereditary or familial cancer syndrome were retrieved. The original slides and hMLH1, hPMS2, hMSH2, hMSH6 immunohistochemistry were evaluated. Tumors with an absence of at least one protein were considered dMMR. Differences were contrasted, utilizing non-parametric tests. RESULTS: One hundred and forty-four patients were included, with a median age of 65 years. A total of 134/93% patients presented with sporadic CRC, 8/5.6% had a family history of CRC, and 2/1.4% met the diagnostic criteria for hereditary non-polyposis colon cancer, according to the Amsterdam and Bethesda criteria. dMMR tumors were found in 39 patients, distributed among the three groups. They were locally advanced (p<0.001), right-sided, had the mucinous phenotype, and harbored a Crohn's-like lymphoid reaction (all three features, p<0.04). Adjuvant or palliative chemotherapy was administered to 57 (39.6%), concomitant chemoradiotherapy to 24 (16.7%), but 63 (43.8%) patients received no additional treatment to surgery. Five-year follow-up was completed in 131 of the patients and the outcomes alive-with-disease or died-of-disease were more frequently observed in the proficient (pMMR) lesions. CONCLUSIONS: In the present pre-FOLFOX case series, outcomes were better in dMMR CRC than in proficient lesions.

Acute Kidney Injury and Urinary and Histopathological Disorders in Kidney Transplant Patients with SARS-CoV-2 Infection.

BACKGROUND: Acute kidney injury (AKI) is a manifestation of SARS-CoV-2 infection. The evidence in kidney transplant (KT) is limited, as there are scarce data about the histologic features in graft biopsies of these patients. MATERIAL AND METHODS: A retrospective cohort study of KTs with SARS-CoV-2 infection from August 28, 2020, to April 23, 2021. We collected the incidence of AKI and the presence of urinary and histopathological disorders. Both groups were compared (AKI vs no AKI). Immunohistochemical and reverse transcription-polymerase chain reaction studies were performed on the anatomopathological samples. RESULTS: In our study, 72 KTs had SARS-CoV-2 infection and, among them, 27 patients (35.1%) developed AKI related to increased severity and a worse evolution of the infection, defined by a greater presence of pneumonia (P < .001), hospitalization (P < .001), admission to the intensive care unit (P < .001), the need for ventilation support (P < .001), and continuous renal replacement therapy (P < .001). In the multivariable analysis, pneumonia behaved as an independent predictor for AKI development (P = .046). No differences were observed between proteinuria a month before and after infection (P = .224). In addition, 5 patients showed microhematuria and 2 patients presented transient glycosuria without hyperglycemia. Of the 5 kidney biopsies performed, 1 biopsy (20%) showed positive reverse transcription polymerase chain reaction for SARS-CoV-2. CONCLUSIONS: AKI is a frequent and potentially serious complication in KT patients. Occasionally it could be accompanied by abnormalities in the urinary sediment. Of 5 biopsied patients, 1 patient had positive reverse transcription polymerase chain reaction in renal tissue, which suggests the systemic spread of the virus and the tropism for the renal graft.

Miopericardite com arritmia complexa após quadro assintomático de COVID19 em atleta de futebol profissional / Myopericarditis with complex arrhythmia after asymptomatic COVID19 in a professional soccer player

INTRODUÇÃO: A avaliação cardiológica para o retorno da prática de atividade físico- -esportiva ganhou destaque durante a pandemia de sars-cov2, visto que o sistema cardiovascular pode ser acometido em 20-30% dos casos de covid-19, com manifestações clínicas que incluem miocardite, síndrome coronariana aguda, insuficiência cardíaca, dentre outras, podendo aumentar o risco de eventos cardiovasculares, em especial a morte súbita, durante a atividade física. Neste relato explicitamos o papel da avaliação pré-participação em atletas após infecção pelo sars-cov 2. MÉTODOS: Relato de caso de paciente masculino de 36 anos, atleta profissional de futebol, previamente hígido, sem história familiar de evento cardiovascular precoce ou morte súbita, atendido no instituto dante pazzanese de cardiologia em 2021 por perda de capacidade funcional vista no retorno aos treinos, 10 dias após quadro assintomático de covid-19 em janeiro de 2021. RESULTADOS: Em fevereiro de 2021 realizou tais exames: eletrocardiograma (ecg) que apresentou onda t invertida em parede inferior e derivações v3-v6, comparados ao ecg basal, o qual era normal; ecocardiograma transtorácico (eco-tt) que evidenciou fração de ejeção ventricular (feve) de 69% e derrame pericárdico laminar anterior; á ressonância magnética cardíaca apresentou realce tardio epicárdico no segmento inferolateral das porções basal e média do ventrículo esquerdo (ve), sugestivo de fibrose miocárdica. Devido quadro de miopericardite, optado por afastamento das atividades físicas. Em junho de 2021, retornou com eco-tt com queda da feve para 50% e alteração de strain longitudinal global (slg) (17%), teste cardiopulmonar evidenciando taquicardica ventricular não sustentada, apesar de excelente aptidão cardiorrespiratória. Foi então iniciado metoprolol e enalapril por início de disfunção de ve. Já em setembro de 2021 retorna com eco-tt mostrando melhora de feve para 63% e melhora do strain (slg) para 21%, entretanto mantendo ao teste ergométrico ectopias ventriculares polimórficas bigeminadas durante esforço e recuperação. Segue em acompanhamento, afastado das atividades físicas, com dose otimizada de beta bloqueador. CONCLUSÃO: Apresentamos um caso de miopericardite adquirida após covid-19 em atleta, evoluindo com alterações de alto risco para morte súbita arritmogênica. Devido a grande taxa de infecções causadas pelo covid 19, reiteramos a importância da avaliação cardiológica para retorno as atividades físico esportivas após tal infecção, mesmo que assintomática, com objetivo de evitar a morte súbita.

Manutenção do ritmo sinusal após retorno à prática esportiva em paciente com fibrilação atrial tratado com descondicionamento / Maintenance of sinus rhythm after return to sports practice in a patient with atrial fibrillation treated with deconditioning

O exercício físico reduz risco de doenças cardiovasculares, metabólicas e está relacionada a aumento do bem-estar e longevidade. Alguns estudos sugerem redução do risco de arritmias, como a fibrilação atrial, em até 19% em homens e 9% em mulheres. Contudo, observa-se prevalência superior, de até 3,5 vezes, de desenvolvimento de fibrilação atrial em praticantes de exercícios de muito alta intensidade ou competitiva, tornando essa a arritmia mais frequente no atleta. Os indivíduos sob maior risco são homens, praticantes de endurance de alta intensidade e com alto volume. A presença de fibrilação atrial, ainda que paroxística, impacta negativamente sobre a capacidade funcional e performance nesses indivíduos, seja pela redução do débito cardíaco pela perda da contração atrial ou pela perda de controle da frequência cardíaca pelo sistema nervoso autônomo. A evidência atual disponível para guiar o manejo desses pacientes se baseia em estudos randomizados em pacientes portadores de FA não atletas, estudos menores em atletas ou em consenso de especialista e o tratamento se baseia nos pilares de controle de ritmo farmacológico ou intervencionista por meio de ablação por radiofrequência ou destrainamento. Esse relato de caso tem como objetivo apresentar a evolução de paciente atleta com fibrilação atrial tratado de forma não invasiva, com destreinamento, de forma a revisar e ampliar o conhecimento sobre o tema. RELATO DE CASO: Paciente, sexo masculino, 42 anos, sem comorbidades prévias, pratica esporte competitivo desde os 15 anos nas modalidades: mountain bike, triátlon e maratona. Procura atendimento médico, sem queixas, solicitando liberação para realização de prova triathlon ironman. Ao exame físico apresentava ausculta cardíaca com frequência de 50 bpm e ritmo irregular, sem outras alterações. O eletrocardiograma apresentava ritmo de fibrilação atrial com baixa resposta ventricular. Foi realizada investigação de cardiopatia estrutural com ecocardiograma que revelou átrio esquerdo aumentado, com volume indexado de 40ml/ m2. Função biventricular preservada. Sem outros achados. Em teste ergométrico, apresentava resposta adequada da frequência cardíaca ao esforço, com excelente capacidade funcional e sem alterações sugestivas de isquemia. Holter evidenciava apenas presença de fibrilação atrial. Foi optado então por tratamento com destreinamento por 3 meses. Após, paciente realizou holter que apresentava ritmo sinusal. Foi mantido seguimento por um ano, com repetição de holter 24h que se manteve em ritmo sinusal.

Avaliação da prática esportiva em atleta jovem com estenose aórtica subvalvar corrigida / Evaluation of sports practice in a young athlete with corrected subvalvular aortic stenosis

Paciente 18 anos, sexo masculino, sem outras comorbidades, ex-atleta amador praticante de Rugby, interrompeu a prática esportiva por orientação médica após o diagnóstico de estenose subvalvar aórtica grave, com gradiente médio de 81 mmHg e máximo de 158 mmHg em membrana subvalvar. Foi realizada correção cirúrgica com ressecção da membrana subaórtica associada à ressecção muscular da via de saída do ventrículo esquerdo e plastia da valva tricúspide. Após recuperação cirúrgica paciente, mantém-se assintomático e retorna periodicamente para avaliação quanto a prática de atividade física e esportiva competitiva. Três anos após cirurgia, em avaliação complementar, ao ecocardiograma, observava-se persistência de prega ventrículo-infundibular e resquício de membrana, determinando estreitamento da via de saída do ventrículo esquerdo (VE), com aceleração de fluxo gerando gradiente sistólico máximo entre VE e aorta de 42 mmHg e médio de 24 mmHg. Refluxo aórtico discreto a moderado. Função sistólica biventricular preservada, hipertrofia ventricular esquerda discreta. Foi solicitado também ecocardiograma com estresse físico que não mostrou sinais de isquemia miocárdica. Membrana subaórtica gerou obstrução importante com repercussão hemodinâmica ao esforço físico. Por fim, realizou teste ergométrico, que apresentou Infradesnivelamento de segmento ST de 2,5mm horizontam em MC5, sem dor, com comportamento adequado da pressão e da frequência cardíaca durante o esforço e capacidade funcional estimada de 13 METs. Após exames complementares, foi realizado reunião com especialistas em cardiologia do esporte e liberado para a prática de atividade física moderada, com cálculo de frequência máxima até 60% da FC reserva e resistiva com até 50% da força máxima. A estenose subvalvar aórtica é uma cardiopatia congênita relativamente frequente que resulta de uma anormalidade subjacente na arquitetura da via de saída do ventrículo esquerdo (VSVE), com fluxo turbilhonado levando à fibrose progressiva dessa região. Obstrução significativa da VSVE leva à hipertrofia ventricular e função hiperdinâmica. É a segunda causa mais comum de estenose aórtica na população pediátrica e muitos pacientes têm regurgitação aórtica associada. A correção cirúrgica geralmente é indicada a partir da 2ª década de vida e 20 até 30% dos pacientes evoluem com recorrência da obstrução. Em virtude da prevalência dessa condição em indivíduos jovens, além de outras condições de risco, a avaliação médica por especialista antes da prática esportiva competitiva torna-se essencial.

Insuficiência cardíaca de fração de ejeção reduzida após infarto agudo do miocárdio em atleta de endurance: é possível continuar no esporte? / Heart failure with reduced ejection fraction after acute myocardial infarction in an endurance athlete: is it possible to continue in sport?

Insuficiência cardíaca é das principais doenças resultando em redução da capacidade física, sendo a doença arterial coronariana sua principal causa, especialmente em atletas acima de 35 anos. Será que insuficiência cardíaca com fração de ejeção reduzida após infarto agudo miocárdio teria espaço no esporte? Paciente masculino, 56 anos, com antecedente de hipertensão arterial sistêmica, previamente atleta de corrida de rua desde 38 anos de idade (meia maratona com pace médio de 3:50 min/km) procurou atendimento em pronto socorro em março de 2016 por angina típica em repouso. Ficou em observação e liberado após analgesia. Por manter dispneia iniciou acompanhamento com cardiologista e, 2 meses após episódio de dor torácica, realizou cintilografia de perfusão miocárdica com tecnécio sestamibi associado a teste ergométrico, evidenciando hipocaptação persistente extensa em parede anterosseptal, inferosseptal e ápice de ventrículo esquerdo (VE), sem hipocaptação transitória e com fração de ejeção de VE (FEVE) de 30%. Realizada estratificação invasiva mostrando lesão de 99% em segmento médio de artéria descendente anterior com aspecto de recanalização e fluxo TIMI um com acinesia de parede anterior discinesia de parede apical. Paciente encaminhado ao serviço terciário e optado por realizar cintilografia miocárdica com tálio-201 e estresse com teste ergométrico que resultou em ausência de isquemia e de viabilidade miocárdica. Portanto, paciente foi mantido em tratamento clínico e reabilitação cardiovascular. Em acompanhamento ambulatorial após seis anos do evento, atualmente praticando corrida dois a três vezes por semana (10 a 12 km com pace 6:15 min/km), com ecocardiograma transtorácico com aumento biatrial e discreto de VE, FEVE 38% com acinesia do segmento médio do septo e do segmento apical de todas as paredes, insuficiência mitral discreta a moderada por remodelamento ventricular. Teste ergométrico realizado com protocolo de Ellestad, interrompido após 12'45" por exaustão e atingindo 98% da frequência cardíaca máxima preconizada pela idade, sem alterações sugestivas de isquemia, extrassístoles ventriculares isoladas e raras e consumo máximo estimado de oxigênio de 56 ml/kg/min, em uso de betabloqueador. Apesar do paciente apresentar excelente aptidão cardiorrespiratória, foi orientado manter atividades de leve a moderada intensidade (70% da reserva cronotrópica) devido a FEVE reduzida. Portanto, há espaço para esses pacientes no esporte não competitivo: após reabilitação cardiovascular, estratificação de risco e contínuo acompanhamento médico e multidisciplinar.

Vulnerabilidade de placa coronariana com teste funcional normal contraindica exercício físico de alta intensidade? / Coronary plaque vulnerability with normal functional test contraindicate high-intensity physical exercise?

Doença arterial coronariana (DAC) é a principal causa de morte súbita em atletas com mais de 35 anos. Sedentarismo é um fator de risco para DAC porém há evidências de que atividade física vigorosa aumente o risco de eventos cardiovasculares de forma paradoxal. Segundo diretrizes, pacientes nos quais DAC é detectada em exames de screening devem ser restringidos de esportes de alta intensidade quando houver alteração em testes funcionais ou quando houver evidência de progressão de doença em avaliação seriada. No entanto, será que lesões coronarianas com teste funcional negativo porém com características de vulnerabilidade contraindicam atividade física intensa em esportistas?. Trazemos o caso de J.B., 59 anos feminina, hipertensa, dislipidêmica, história familiar de DAC precoce. Esportista, pratica corrida quatro vezes por semana, musculação três vezes por semana e ciclismo duas vezes por semana, em alta intensidade. Em avaliação pré-participação para maratona em serviço externo foi submetida a angiotomografia de coronárias evidenciando escore de cálcio 1772 (p99) com placas calcificadas e redução luminal importante em terço proximal de descendente anterior (DA) e diagonal (DG), e redução luminal discreta de artéria circunflexa (CX), e oclusão total em terço proximal de artéria coronária direita (CD). Ao cateterismo, confirmadas as lesões de 40% em terço médio CD, 70% em terço proximal de DA, 80% diagonal e 40% CX. Em nosso serviço foi submetida a cintilografia de perfusão miocárdica SPECT 99m-Tc precedida de teste de esforço. Não houve sinais de isquemia à imagem e o teste de esforço teve comportamento normal de PA, FC, ausência de arritmia ou de alteração de segmento ST ou sintomas, e desempenho de 12,9 METS, VO2 de 45. O caso foi discutido com conjunto com o setor de tomografia, coronariopatias, hemodinâmica e cardiologia do esporte, sendo contraindicada exercício físico de alta intensidade devido ao achado de vulnerabilidade de placas à angiotomografia e cateterismo, evidência ainda pouco debatida na literatura mundial.

Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States.

Endothelial nitric oxide synthase (eNOS) plays a critical role in regulating and maintaining a healthy cardiovascular system. The importance of eNOS can be emphasized from the genetic polymorphisms of the eNOS gene, uncoupling of eNOS dimerization, and its numerous signaling regulations. The activity of eNOS on the cardiac myocytes, vasculature, and the central nervous system are discussed. The effects of eNOS on the sympathetic autonomic nervous system (SANS) and the parasympathetic autonomic nervous system (PANS), both of which profoundly influence the cardiovascular system, will be elaborated. The relationship between the eNOS protein with cardiovascular autonomic reflexes such as the baroreflex and the Exercise Pressor Reflex will be discussed. For example, the effects of endogenous nitric oxide (NO) are shown to be mediated by the eNOS protein and that eNOS-derived endothelial NO is most effective in regulating blood pressure oscillations via modulating the baroreflex mechanisms. The protective action of eNOS on the CVS is emphasized here because dysfunction of the eNOS enzyme is intricately correlated with the pathogenesis of several cardiovascular diseases such as hypertension, arteriosclerosis, myocardial infarction, and stroke. Overall, our current understanding of the eNOS protein with a focus on its role in the modulation, regulation, and control of the cardiovascular system in a normal physiological state and in cardiovascular diseases are discussed.