Electrocontractile remodeling of isolated cardiomyocytes induced during early-stage hypercholesterolemia.

Hypercholesterolemia is one of the most important risk factors for cardiovascular diseases. However, it is mostly associated with vascular dysfunction and atherosclerotic lesions, while evidence of direct effects of hypercholesterolemia on cardiomyocytes and heart function is still incomplete and controversial. In this study, we assessed the direct effects of hypercholesterolemia on heart function and the electro-contractile properties of isolated cardiomyocytes. After 5 weeks, male Swiss mice fed with AIN-93 diet added with 1.25% cholesterol (CHO), developed an increase in total serum cholesterol levels and cardiomyocytes cholesterol content. These changes led to altered electrocardiographic records, with a shortening of the QT interval. Isolated cardiomyocytes displayed a shortening of the action potential duration with increased rate of depolarization, which was explained by increased IK, reduced ICa.L and altered INa voltage-dependent inactivation. Also, reduced diastolic [Ca2+]i was found with preserved adrenergic response and cellular contraction function. However, contraction of isolated hearts is impaired in isolated CHO hearts, before and after ischemia/reperfusion, although CHO heart was less susceptible to arrhythmic contractions. Overall, our results demonstrate that early hypercholesterolemia-driven increase in cellular cholesterol content is associated with direct modulation of the heart and cardiomyocytes' excitability, Ca2+ handling, and contraction.

Covid-19 and Sargassum blooms: impacts and social issues in a mass tourism destination (Mexican Caribbean).

When the COVID-19 pandemic reached the Mexican Caribbean in late March 2020, this world-renown tourist destination had already been struggling with Sargassum influxes for 5 years. The nature and magnitude of these two impacts are not directly comparable, but both have contributed to profoundly transforming the region. As extreme COVID-19 containment measures were implemented nationwide, the tourism industry contracted by 98% as over 23 million visitors failed to arrive in 2020 and 400 daily flights stopped landing at Cancun Airport. Sargassum accumulations on Caribbean beaches, and their collection, containment and removal had been a challenging socioeconomic issue in the Caribbean region years before the COVID-19 pandemic shut down the tourist industry. We explore Beck's concept of a risk society as an approach to these socioenvironmental impacts. We analyze five premises about risk society, combining them with a mainly ethnography methodology involving 61 informants. We present the results in terms of impacts. Using the concept of trajectory based on pandemic event chronology, we review the main stages of the pandemic during the research period (May to July 2020) and how the studied population worked to prevent virus infection and spread. We employ narratives to analyze risk perception both of the Sargassum influx and the pandemic. The discussion highlights the importance of moving beyond nature/society dichotomies and dualisms. In summary, the profound transformations caused by these impacts provide a unique opportunity for the Mexican Caribbean to reconstitute itself in a way that encompasses the world risk society concept, perhaps in a more socially and environmentally resilient incarnation.

High Serum Netrin-1 and IL-1ß in Elderly Females with ACS: Worse Prognosis in 2-years Follow-up. / Níveis Elevados de Netrina-1 e IL-1ß em Mulheres Idosas com SCA: Pior Prognóstico no Acompanhamento de Dois Anos.

BACKGROUND: Several markers have been evaluated for a potential impact on clinical decisions or mortality prediction in acute coronary syndrome (ACS), including Netrin-1 and IL-1ß that have been associated with cardiovascular disease. OBJECTIVE: Our study examined the prognostic value of Netrin-1 and IL-1ß in patients with ACS (2-year follow-up). METHODS: We evaluate Netrin-1, IL-1ß and other risk factors in the serum sample of 803 patients. Kaplan-Meier curves and Cox regression were used for the analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction (MI) or new non-fatal MI, considering p-value < 0.05. RESULTS: There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. Netrin-1 levels above the median (>44.8 pg/mL) were associated with a worse prognosis (all-cause mortality and cardiovascular mortality) in elderly females, even after model adjustment (HR: 2.08, p = 0.038 and HR: 2.68, p = 0.036). IL-1ß levels above the median (>13.4 pg/mL) in elderly females were associated with increased risk of all outcomes after adjustment (all-cause mortality - HR: 2.03, p = 0.031; cardiovascular mortality - HR: 3.01, p = 0.013; fatal MI or new non-fatal MI - HR: 3.05, p = 0.029). For males, no associations were observed between Netrin-1 or IL-1ß and outcomes. CONCLUSION: High serum levels of Netrin-1 and IL-1ß showed significant association with worse prognosis in elderly females. They may be useful as prognostic indicators in ACS. (Arq Bras Cardiol. 2020; 114(3):507-514).

FUNDAMENTO: Vários marcadores têm sido avaliados quanto a um potencial impacto nas decisões clínicas ou na predição de mortalidade na síndrome coronariana aguda (SCA), incluindo Netrina-1 e IL-1ß. OBJETIVO: Examinamos o valor prognóstico de Netrina-1 e IL-1ß em pacientes com SCA (2 anos de acompanhamento). MÉTODOS: Avaliamos Netrina-1, IL-1ß e outros fatores de risco em amostras de soro de 803 pacientes. Curvas de Kaplan-Meier e regressão de Cox foram usadas para análise de óbito por todas as causas, óbito por doenças cardiovasculares (DCV) e desfecho combinado de infarto agudo do miocárdio (IAM) fatal ou novo IAM não fatal, considerando p < 0,05. RESULTADOS: Houve 115 óbitos por todas as causas, 78 óbitos por DCV e 67 eventos no desfecho combinado. Níveis de Netrina-1 acima da mediana (> 44,8 pg/mL) foram associados a pior prognóstico (óbito por todas as causas e por DCV) em mulheres idosas, mesmo após o ajuste do modelo (HR: 2,08, p = 0,038 e HR: 2,68, p = 0,036). Níveis de IL-1ß acima da mediana (> 13,4 pg/mL) em mulheres idosas foram associados a risco aumentado para todos os desfechos após o ajuste (todas as causas - HR: 2,03, p = 0,031; DCV - HR: 3,01, p = 0,013; desfecho combinado - HR: 3,05, p = 0,029). Para homens, não foram observadas associações entre Netrina-1 ou IL-1ß e os desfechos. CONCLUSÃO: Níveis séricos elevados de Netrina-1 e IL-1ß mostraram associação significativa com pior prognóstico em idosas do sexo feminino. Eles podem ser úteis como indicadores prognósticos em SCA. (Arq Bras Cardiol. 2020; 114(3):507-514).

Níveis Elevados de Netrina-1 e IL-1β em Mulheres Idosas com SCA: Pior Prognóstico no Acompanhamento de Dois Anos / High Serum Netrin-1 and IL-1β in Elderly Females with ACS: Worse Prognosis in 2-years Follow-up

Resumo Fundamento Vários marcadores têm sido avaliados quanto a um potencial impacto nas decisões clínicas ou na predição de mortalidade na síndrome coronariana aguda (SCA), incluindo Netrina-1 e IL-1β. Objetivo Examinamos o valor prognóstico de Netrina-1 e IL-1β em pacientes com SCA (2 anos de acompanhamento). Métodos Avaliamos Netrina-1, IL-1β e outros fatores de risco em amostras de soro de 803 pacientes. Curvas de Kaplan-Meier e regressão de Cox foram usadas para análise de óbito por todas as causas, óbito por doenças cardiovasculares (DCV) e desfecho combinado de infarto agudo do miocárdio (IAM) fatal ou novo IAM não fatal, considerando p < 0,05. Resultados Houve 115 óbitos por todas as causas, 78 óbitos por DCV e 67 eventos no desfecho combinado. Níveis de Netrina-1 acima da mediana (> 44,8 pg/mL) foram associados a pior prognóstico (óbito por todas as causas e por DCV) em mulheres idosas, mesmo após o ajuste do modelo (HR: 2,08, p = 0,038 e HR: 2,68, p = 0,036). Níveis de IL-1β acima da mediana (> 13,4 pg/mL) em mulheres idosas foram associados a risco aumentado para todos os desfechos após o ajuste (todas as causas - HR: 2,03, p = 0,031; DCV - HR: 3,01, p = 0,013; desfecho combinado - HR: 3,05, p = 0,029). Para homens, não foram observadas associações entre Netrina-1 ou IL-1β e os desfechos. Conclusão Níveis séricos elevados de Netrina-1 e IL-1β mostraram associação significativa com pior prognóstico em idosas do sexo feminino. Eles podem ser úteis como indicadores prognósticos em SCA. (Arq Bras Cardiol. 2020; 114(3):507-514)

Abstract Background Several markers have been evaluated for a potential impact on clinical decisions or mortality prediction in acute coronary syndrome (ACS), including Netrin-1 and IL-1β that have been associated with cardiovascular disease. Objective Our study examined the prognostic value of Netrin-1 and IL-1β in patients with ACS (2-year follow-up). Methods We evaluate Netrin-1, IL-1β and other risk factors in the serum sample of 803 patients. Kaplan-Meier curves and Cox regression were used for the analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction (MI) or new non-fatal MI, considering p-value < 0.05. Results There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. Netrin-1 levels above the median (>44.8 pg/mL) were associated with a worse prognosis (all-cause mortality and cardiovascular mortality) in elderly females, even after model adjustment (HR: 2.08, p = 0.038 and HR: 2.68, p = 0.036). IL-1β levels above the median (>13.4 pg/mL) in elderly females were associated with increased risk of all outcomes after adjustment (all-cause mortality - HR: 2.03, p = 0.031; cardiovascular mortality - HR: 3.01, p = 0.013; fatal MI or new non-fatal MI - HR: 3.05, p = 0.029). For males, no associations were observed between Netrin-1 or IL-1β and outcomes. Conclusion High serum levels of Netrin-1 and IL-1β showed significant association with worse prognosis in elderly females. They may be useful as prognostic indicators in ACS. (Arq Bras Cardiol. 2020; 114(3):507-514)

Prehospital selection of thrombectomy candidates beyond large vessel occlusion: M-DIRECT scale.

OBJECTIVE: Current prehospital scales used to detect large vessel occlusion reveal very low endovascular thrombectomy (EVT) rates among selected patients. We developed a novel prehospital scale, the Madrid-Direct Referral to Endovascular Center (M-DIRECT), to identify EVT candidates for direct transfer to EVT-capable centers (EVT-Cs). The scale evaluated clinical examination, systolic blood pressure, and age. Since March 2017, patients closer to a stroke unit without EVT capabilities and an M-DIRECT positive score have been transferred to the nearest EVT-C. To test the performance of the scale-based routing protocol, we compared its outcomes with those of a simultaneous cohort of patients directly transferred to an EVT-C. METHODS: In this prospective observational study of consecutive patients with stroke code seen by emergency medical services, we compared diagnoses, treatments, and outcomes of patients who were closer to an EVT-C (mothership cohort) with those transferred according to the M-DIRECT score (M-DIRECT cohort). RESULTS: The M-DIRECT cohort included 327 patients and the mothership cohort 214 patients. In the M-DIRECT cohort, 227 patients were negative and 100 were positive. Twenty-four (10.6%) patients required secondary transfer, leaving 124 (38%) patients from the M-DIRECT cohort admitted to an EVT-C. EVT rates were similar for patients with ischemic stroke in both cohorts (30.9% vs 31.5%). The M-DIRECT scale had 79% sensitivity, 82% specificity, and 53% positive predictive value for EVT. Recanalization and independence rates at 3 months did not differ between the cohorts. CONCLUSIONS: The M-DIRECT scale was highly accurate for EVT, with treatment rates and outcomes similar to those of a mothership paradigm, thereby avoiding EVT-C overload with a low rate of secondary transfers.

Wheat gluten intake increases the severity of experimental colitis and bacterial translocation by weakening of the proteins of the junctional complex.

Gluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and ß-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.

Low serum levels of CCL2 are associated with worse prognosis in patients with Acute Coronary Syndrome: 2-year survival analysis.

Inflammation is very important in Acute Coronary Syndrome (ACS) as well as in cardiac remodeling after an acute myocardial infarction (MI). Our study examined the prognostic value of Chemokine (C-C motif) ligand 2 (CCL2) in patients with ACS in the ERICO (Strategy of Registry of Acute Coronary Syndrome) study. We evaluated serum samples from 803 patients. The prognostic value of CCL2 was evaluated at the 2-year follow-up, according to cutoff points established by the median. Kaplan-Meier curves and Cox regression were used for analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction or new non-fatal MI. There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. CCL2 levels below the median (≤100.9 pg/mL) were associated with increased risk of MI death or new non-fatal MI, even after model adjustment. Low serum levels of CCL2 shows a significant association with fatal or new non-fatal MI.

Patologias genitais masculinas em cirurgia pediátrica de manejo / Outpatient pediatric surgery of male genital pathologies

Objetivos: Diagnosticar e manejar patologias comuns do trato genital masculino. Métodos: Revisão da literatura do ano de 2011 ao 2017 em base de dados PubMed. Resultados: Hipospádia é a localização anômala do meato uretral. Seu diagnóstico é clínico. As indicações cirúrgicas são anormalidades funcionais e estéticas. Fimose é descrita como impossibilidade de retração do prepcio para exposição da glande peniana, sendo um evento fisiológico quando apresenta resolução espontânea. Nos casos patológicos, o tratamento é primeiramente realizado com corticoide tópico. Se falha, o tratamento é cirúrgico. Hidrocele é o acúmulo de líquido na bolsa escrotal. O diagnóstico é clínico e por transiluminação escrotal. A maioria dos casos regride espontaneamente até os 24-36 meses. A cirurgia é considerada padrão-ouro para hidrocele comunicante na criança. Criptorquidia é a falha na migração do testículo até a bolsa escrotal. Seu diagnóstico é clínico, através da palpação testicular bilateral. Caso os testículos não estejam presentes na bolsa escrotal até os 6 meses de idade, a cirurgia é imprescindível, pelo risco de infertilidade e malignização. Conclusões: É essencial que o médico generalista saiba reconhecer tais condições com o intuito de iniciar prontamente o tratamento adequado, evitando suas complicações.

Aims: Diagnose and manage common pathologies of the male genital tract. Methods: Literary review of the last 6 years in the PubMed database. Results: Hypospadia is an anomalous location of the urethral meatus. The diagnosis is clinical. Surgical indications are functional and aesthetic abnormalities. Fimosis is described as impossibility of retraction of the foreskin to expose the penile glans, it is a physiological event when it presents spontaneous resolution. In pathological cases, treatment is first performed with topical corticosteroids. If it fails, the treatment is surgical. Hydrocele is the accumulation of fluid in the scrotal sac. The diagnosis is clinical and scrotal transillumination. Most cases regress spontaneously up to 24-36 months. Surgery is considered gold standard in cases of communicant hydrocele in children. Cryptorchidism is the failure of the migration of the testis to scrotal sac. The diagnosis is clinical through bilateral testicular palpation. If the testicles are not present in the scrotal sac until 6 months of age, surgery is essential, due to the risk of infertility and malignancy. Conclusions: It is imperative that the general practitioner knows how to recognize such conditions in order to promptly initiate appropriate treatment, avoiding complications.

Diving behavior and fishing performance: the case of lobster artisanal fishermen of the Yucatan coast, Mexico.

An average of 209 cases of decompression sickness (DCS) have been reported every year among artisanal fishermen. divers of the Yucatan Peninsula, Mexico. DCS is a major problem among fishermen divers worldwide. This paper explores how diving behavior and fishing techniques among fishermen relate to the probability of experiencing DCS (Pdcs). Fieldwork was conducted in two communities during the 2012-2013 fishing season. Fishermen were classified into three groups (two per group) according to their fishing performance and followed during their journeys. Dive profiles were recorded using Sensus Ultra dive recorders (Reefet Inc.). Surveys were used to record fishing yields from cooperative and individual fishermen along with fishing techniques and dive behavior. 120 dives were recorded. Fishermen averaged three dives/day, with an average depth of 47 ± 2 feet of sea water (fsw) and an average total bottom time (TBT) of 95 ± 11 minutes. 24% of dives exceeded the 2008 U.S. Navy no-decompression limit. The average ascent rate was 20 fsw/minute, and 5% of those exceeded 40 fsw/minute. Inadequate decompression was observed in all fishermen. Fishermen are diving outside the safety limits of both military and recreational standards. Fishing techniques and dive behavior were important factors in Pdcs. Fishermen were reluctant to seek treatment, and symptoms were relieved with analgesics.