Sleep staging algorithm based on smartwatch sensors for healthy and sleep apnea populations.

OBJECTIVE: Sleep stages can provide valuable insights into an individual's sleep quality. By leveraging movement and heart rate data collected by modern smartwatches, it is possible to enable the sleep staging feature and enhance users' understanding about their sleep and health conditions. METHOD: In this paper, we present and validate a recurrent neural network based model with 23 input features extracted from accelerometer and photoplethysmography sensors data for both healthy and sleep apnea populations. We designed a lightweight and fast solution to enable the prediction of sleep stages for each 30-s epoch. This solution was developed using a large dataset of 1522 night recordings collected from a highly heterogeneous population and different versions of Samsung smartwatch. RESULTS: In the classification of four sleep stages (wake, light, deep, and rapid eye movements sleep), the proposed solution achieved 71.6 % of balanced accuracy and a Cohen's kappa of 0.56 in a test set with 586 recordings. CONCLUSION: The results presented in this paper validate our proposal as a competitive wearable solution for sleep staging. Additionally, the use of a large and diverse data set contributes to the robustness of our solution, and corroborates the validation of algorithm's performance. Some additional analysis performed for healthy and sleep apnea population demonstrated that algorithm's performance has low correlation with demographic variables.

A Framework for Implementing Disease Prevention and Behavior Change Evidence at Scale.

The current corpus of evidence-based information for chronic disease prevention and treatment is vast and growing rapidly. Behavior change theories are increasingly more powerful but difficult to operationalize in the current healthcare system. Millions of Canadians are unable to access personalized preventive and behavior change care because our in-person model of care is running at full capacity and is not set up for mass education and behavior change programs. We propose a framework to utilize data from electronic medical records to identify patients at risk of developing chronic disease and reach out to them using digital health tools that are overseen by the primary care team. The framework leverages emerging technologies such as artificial intelligence, digital health tools, and patient-generated data to deliver evidence-based knowledge and behavior change to patients across Canada at scale. The framework is flexible to enable new technologies to be added without overwhelming providers, patients or implementers.

Exaggerated Exercise Blood Pressure as a Marker of Baroreflex Dysfunction in Normotensive Metabolic Syndrome Patients.

INTRODUCTION: Exaggerated blood pressure response to exercise (EEBP = SBP ≥ 190 mmHg for women and ≥210 mmHg for men) during cardiopulmonary exercise test (CPET) is a predictor of cardiovascular risk. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) seem to be involved in the progression of metabolic syndrome (MetS) to cardiovascular disease. OBJECTIVE: To test the hypotheses: (1) MetS patients within normal clinical blood pressure (BP) may present EEBP response to maximal exercise and (2) increased muscle sympathetic nerve activity (MSNA) and reduced BRS are associated with this impairment. METHODS: We selected MetS (ATP III) patients with normal BP (MetS_NT, n = 27, 59.3% males, 46.1 ± 7.2 years) and a control group without MetS (C, n = 19, 48.4 ± 7.4 years). We evaluated BRS for increases (BRS+) and decreases (BRS-) in spontaneous BP and HR fluctuations, MSNA (microneurography), BP from ambulatory blood pressure monitoring (ABPM), and auscultatory BP during CPET. RESULTS: Normotensive MetS (MetS_NT) had higher body mass index and impairment in all MetS risk factors when compared to the C group. MetS_NT had higher peak systolic BP (SBP) (195 ± 17 vs. 177 ± 24 mmHg, P = 0.007) and diastolic BP (91 ± 11 vs. 79 ± 10 mmHg, P = 0.001) during CPET than C. Additionally, we found that MetS patients with normal BP had lower spontaneous BRS- (9.6 ± 3.3 vs. 12.2 ± 4.9 ms/mmHg, P = 0.044) and higher levels of MSNA (29 ± 6 vs. 18 ± 4 bursts/min, P < 0.001) compared to C. Interestingly, 10 out of 27 MetS_NT (37%) showed EEBP (MetS_NT+), whereas 2 out of 19 C (10.5%) presented (P = 0.044). The subgroup of MetS_NT with EEBP (MetS_NT+, n = 10) had similar MSNA (P = 0.437), but lower BRS+ (P = 0.039) and BRS- (P = 0.039) compared with the subgroup without EEBP (MetS_NT-, n = 17). Either office BP or BP from ABPM was similar between subgroups MetS_NT+ and MetS_NT-, regardless of EEBP response. In the MetS_NT+ subgroup, there was an association of peak SBP with BRS- (R = -0.70; P = 0.02), triglycerides with peak SBP during CPET (R = 0.66; P = 0.039), and of triglycerides with BRS- (R = 0.71; P = 0.022). CONCLUSION: Normotensive MetS patients already presented higher peak systolic and diastolic BP during maximal exercise, in addition to sympathetic hyperactivation and decreased baroreflex sensitivity. The EEBP in MetS_NT with apparent well-controlled BP may indicate a potential depressed neural baroreflex function, predisposing these patients to increased cardiovascular risk.

Interferon Gamma Induces the Increase of Cell-Surface Markers (CD80/86, CD83 and MHC-II) in Splenocytes From Atlantic Salmon.

Type II interferon gamma (IFNγ) is a pleiotropic cytokine capable of modulating the innate and adaptive immune responses which has been widely characterized in several teleost families. In fish, IFNγ stimulates the expression of cytokines and chemokines associated with the pro-inflammatory response and enhances the production of nitrogen and oxygen reactive species in phagocytic cells. This work studied the effect of IFNγ on the expression of cell-surface markers on splenocytes of Atlantic salmon (Salmo salar). In vitro results showed that subpopulations of mononuclear splenocytes cultured for 15 days were capable of increasing gene expression and protein availability of cell-surface markers such as CD80/86, CD83 and MHC II, after being stimulated with recombinant IFNγ. These results were observed for subpopulations with characteristics associated with monocytes (51%), and features that could be related to lymphocytes (46.3%). In addition, a decrease in the expression of zbtb46 was detected in IFNγ-stimulated splenocytes. Finally, the expression of IFNγ and cell-surface markers was assessed in Atlantic salmon under field conditions. In vivo results showed that the expression of ifnγ increased simultaneously with the up-regulation of cd80/86, cd83 and mhcii during a natural outbreak of Piscirickettsia salmonis. Overall, the results obtained in this study allow us to propose IFNγ as a candidate molecule to stimulate the phenotypic progression of a small population of immune cells, which will increase antigen presenting cells markers. Thereby, modulatory strategies using IFNγ may generate a robust and coordinated immune response in fish against pathogens that affect aquaculture.

Visceral Obesity and High Systolic Blood Pressure as the Substrate of Endothelial Dysfunction in Obese Adolescents. / Obesidade Visceral e Hipertensão Sistólica como Substratos da Disfunção Endotelial em Adolescentes Obesos.

BACKGROUND: Obesity affects adolescence and may lead to metabolic syndrome (MetS) and endothelial dysfunction, an early marker of cardiovascular risk. Albeit obesity is strongly associated with obstructive sleep apnea (OSA), it is not clear the role of OSA in endothelial function in adolescents with obesity. OBJECTIVE: To investigate whether obesity during adolescence leads to MetS and/or OSA; and causes endothelial dysfunction. In addition, we studied the possible association of MetS risk factors and apnea hypopnea index (AHI) with endothelial dysfunction. METHODS: We studied 20 sedentary obese adolescents (OA; 14.2±1.6 years, 100.9±20.3kg), and 10 normal-weight adolescents (NWA, 15.2±1.2 years, 54.4±5.3kg) paired for sex. We assessed MetS risk factors (International Diabetes Federation criteria), vascular function (Flow-Mediated Dilation, FMD), functional capacity (VO2peak) and the presence of OSA (AHI>1event/h, by polysomnography). We considered statistically significant a P<0.05. RESULTS: OA presented higher waist (WC), body fat, triglycerides, systolic (SBP) and diastolic blood pressure (DBP), LDL-c and lower HDL-c and VO2peak than NWA. MetS was presented in the 35% of OA, whereas OSA was present in 86.6% of OA and 50% of EA. There was no difference between groups in the AHI. The OA had lower FMD than NWA (6.17±2.72 vs. 9.37±2.20%, p=0.005). There was an association between FMD and WC (R=-0.506, p=0.008) and FMD and SBP (R=-0.493, p=0.006). CONCLUSION: In adolescents, obesity was associates with MetS and caused endothelial dysfunction. Increased WC and SBP could be involved in this alteration. OSA was observed in most adolescents, regardless of obesity. (Arq Bras Cardiol. 2021; 116(4):795-803).

FUNDAMENTO: A obesidade afeta a adolescência, podendo levar à síndrome metabólica (SM) e disfunção endotelial, um marcador precoce de risco cardiovascular. Apesar de a obesidade ser fortemente associada à síndrome da apneia obstrutiva do sono (SAOS), ainda não está claro o papel da SAOS na função endotelial em adolescentes obesos. OBJETIVO: Investigar se a obesidade durante a adolescência leva à SM e/ou SAOS e causa disfunção endotelial nesses indivíduos. Além disso, estudamos a possível associação dos fatores de risco para SM e do índice de apneia e hipopneia (IAH) com disfunção endotelial. MÉTODOS: Estudamos 20 adolescentes obesos sedentários (AO; 14,2±1,6 anos, 100,9±20,3kg), e 10 adolescentes eutróficos (AE, 15,2±1,2 anos, 54,4±5,3kg) pareados por sexo. Avaliamos os fatores de risco para SM (critérios da Federação Internacional de Diabetes), função vascular (dilatação mediada pelo fluxo, DMF), capacidade funcional (VO2pico) e presença de SAOS (IAH > 1 evento/hora, pela polissonografia). Consideramos um p<0,05 como estatisticamente significativo. RESULTADOS: AO apresentaram maior circunferência da cintura (CC), gordura corporal, triglicerídeos, pressão arterial sistólica (PAS) e diastólica (PAD), maiores níveis de LDL e menores HDL e VO2pico em comparação a AE. Não houve diferença no IAH entre os grupos. AO apresentaram menor DMF que AE (6,17±2,72 vs. 9,37±2,20%, p=0,005). Observou-se uma associação entre DMF e CC (R=-0,506, p=0,008) e entre DMF e PAS (R=-0,493, p=0,006). CONCLUSÃO: Em adolescentes, a obesidade associou-se à SM e causou disfunção endotelial. CC e PAS aumentadas poderiam estar envolvidas nessa alteração. SAOS foi detectada na maioria dos adolescentes independentemente de obesidade. (Arq Bras Cardiol. 2021; 116(4):795-803).

Obesidade Visceral e Hipertensão Sistólica como Substratos da Disfunção Endotelial em Adolescentes Obesos / Visceral Obesity and High Systolic Blood Pressure as the Substrate of Endothelial Dysfunction in Obese Adolescents

Resumo Fundamento: A obesidade afeta a adolescência, podendo levar à síndrome metabólica (SM) e disfunção endotelial, um marcador precoce de risco cardiovascular. Apesar de a obesidade ser fortemente associada à síndrome da apneia obstrutiva do sono (SAOS), ainda não está claro o papel da SAOS na função endotelial em adolescentes obesos. Objetivo: Investigar se a obesidade durante a adolescência leva à SM e/ou SAOS e causa disfunção endotelial nesses indivíduos. Além disso, estudamos a possível associação dos fatores de risco para SM e do índice de apneia e hipopneia (IAH) com disfunção endotelial. Métodos: Estudamos 20 adolescentes obesos sedentários (AO; 14,2±1,6 anos, 100,9±20,3kg), e 10 adolescentes eutróficos (AE, 15,2±1,2 anos, 54,4±5,3kg) pareados por sexo. Avaliamos os fatores de risco para SM (critérios da Federação Internacional de Diabetes), função vascular (dilatação mediada pelo fluxo, DMF), capacidade funcional (VO2pico) e presença de SAOS (IAH > 1 evento/hora, pela polissonografia). Consideramos um p<0,05 como estatisticamente significativo. Resultados: AO apresentaram maior circunferência da cintura (CC), gordura corporal, triglicerídeos, pressão arterial sistólica (PAS) e diastólica (PAD), maiores níveis de LDL e menores HDL e VO2pico em comparação a AE. Não houve diferença no IAH entre os grupos. AO apresentaram menor DMF que AE (6,17±2,72 vs. 9,37±2,20%, p=0,005). Observou-se uma associação entre DMF e CC (R=-0,506, p=0,008) e entre DMF e PAS (R=-0,493, p=0,006). Conclusão: Em adolescentes, a obesidade associou-se à SM e causou disfunção endotelial. CC e PAS aumentadas poderiam estar envolvidas nessa alteração. SAOS foi detectada na maioria dos adolescentes independentemente de obesidade. (Arq Bras Cardiol. 2021; 116(4):795-803)

Abstract Background: Obesity affects adolescence and may lead to metabolic syndrome (MetS) and endothelial dysfunction, an early marker of cardiovascular risk. Albeit obesity is strongly associated with obstructive sleep apnea (OSA), it is not clear the role of OSA in endothelial function in adolescents with obesity. Objective: To investigate whether obesity during adolescence leads to MetS and/or OSA; and causes endothelial dysfunction. In addition, we studied the possible association of MetS risk factors and apnea hypopnea index (AHI) with endothelial dysfunction. Methods: We studied 20 sedentary obese adolescents (OA; 14.2±1.6 years, 100.9±20.3kg), and 10 normal-weight adolescents (NWA, 15.2±1.2 years, 54.4±5.3kg) paired for sex. We assessed MetS risk factors (International Diabetes Federation criteria), vascular function (Flow-Mediated Dilation, FMD), functional capacity (VO2peak) and the presence of OSA (AHI>1event/h, by polysomnography). We considered statistically significant a P<0.05. Results: OA presented higher waist (WC), body fat, triglycerides, systolic (SBP) and diastolic blood pressure (DBP), LDL-c and lower HDL-c and VO2peak than NWA. MetS was presented in the 35% of OA, whereas OSA was present in 86.6% of OA and 50% of EA. There was no difference between groups in the AHI. The OA had lower FMD than NWA (6.17±2.72 vs. 9.37±2.20%, p=0.005). There was an association between FMD and WC (R=-0.506, p=0.008) and FMD and SBP (R=-0.493, p=0.006). Conclusion: In adolescents, obesity was associates with MetS and caused endothelial dysfunction. Increased WC and SBP could be involved in this alteration. OSA was observed in most adolescents, regardless of obesity. (Arq Bras Cardiol. 2021; 116(4):795-803)

Serum Levels of BDNF in Cardiovascular Protection and in Response to Exercise. / Níveis Séricos do BDNF na Proteção Cardiovascular e em Resposta ao Exercício.

Cardiovascular disease (CVD) is currently the leading cause of death in Brazil and worldwide. In 2016, CVD accounted for more than 17 million deaths, representing 31% of all deaths globally. Molecular and genetic mechanisms may be involved in vascular protection and should be considered in new therapeutic approaches. In this sense, recent studies have reported that brain-derived neurotrophic factor (BDNF) is reduced in individuals predisposed to develop CVD, and that aerobic physical training increases the amounts of circulating BDNF. BDNF is a neurotrophin found at high concentrations in the hippocampus and cerebral cortex and is considered a key molecule for the maintenance of synaptic plasticity and survival of neuronal cells. In addition to neuronal plasticity, BDNF is also important in vascular function, promoting angiogenesis through the regulation of reactive oxygen species (ROS). However, a variant of the BDNF gene in humans, the Val66Met polymorphism (substitution of the amino acid valine for a methionine at position 66 of the codon), occurring in 20-30% of the Caucasian population, may affect plasma BDNF concentrations and its activity in all peripheral tissues containing tyrosine kinase B receptors (TrkB), such as the endothelium. Thus, we will present a discussion about the role of serum BDNF levels in cardiovascular protection, Val66Met genetic variant in vascular reactivity and the effect of physical exercise.

As doenças cardiovasculares (DCV) são atualmente a maior causa de morte no Brasil e no mundo. Em 2016 as DCV foram responsáveis por mais de 17 milhões de mortes, representando 31% de todas as mortes em nível global. Mecanismos moleculares e genéticos podem estar envolvidos na proteção cardiovascular e devem ser considerados nas novas abordagens terapêuticas. Nesse sentido, recentes estudos têm relatado que o Fator Neurotrófico Derivado do Encéfalo (Brain-Derived Neurotrophic Factor, BDNF) está reduzido em indivíduos predispostos a desenvolverem DCV, e que o treinamento físico aeróbio aumenta as quantidades de BDNF circulante. O BDNF é uma neurotrofina encontrada em altas concentrações no hipocampo e córtex cerebral, sendo considerada molécula-chave na manutenção da plasticidade sináptica e na sobrevivência das células neuronais. Além da plasticidade neuronal, BDNF também é importante na função vascular, promovendo angiogênese por meio da regulação por espécies reativas de oxigênio (ROS). Entretanto, uma variante do gene do BDNF em humanos, o polimorfismo Val66Met (substituição do aminoácido valina por uma metionina na posição 66 do códon), que ocorre em 20-30% da população caucasiana, pode afetar as concentrações de BDNF no plasma e sua atividade em todos os tecidos periféricos contendo receptores tirosina quinase B (TrkB), como o endotélio. De fato, recentemente observamos que o polimorfismo Val66Met prejudica a reatividade vascular e o BDNF circulante em resposta ao treinamento físico. Dessa forma, apresentaremos a seguir uma discussão sobre os níveis séricos de BDNF na proteção cardiovascular, a variante genética Val66Met na reatividade vascular e o efeito do exercício físico.

Níveis Séricos do BDNF na Proteção Cardiovascular e em Resposta ao Exercício / Serum Levels of BDNF in Cardiovascular Protection and in Response to Exercise

Resumo As doenças cardiovasculares (DCV) são atualmente a maior causa de morte no Brasil e no mundo. Em 2016 as DCV foram responsáveis por mais de 17 milhões de mortes, representando 31% de todas as mortes em nível global. Mecanismos moleculares e genéticos podem estar envolvidos na proteção cardiovascular e devem ser considerados nas novas abordagens terapêuticas. Nesse sentido, recentes estudos têm relatado que o Fator Neurotrófico Derivado do Encéfalo (Brain-Derived Neurotrophic Factor, BDNF) está reduzido em indivíduos predispostos a desenvolverem DCV, e que o treinamento físico aeróbio aumenta as quantidades de BDNF circulante. O BDNF é uma neurotrofina encontrada em altas concentrações no hipocampo e córtex cerebral, sendo considerada molécula-chave na manutenção da plasticidade sináptica e na sobrevivência das células neuronais. Além da plasticidade neuronal, BDNF também é importante na função vascular, promovendo angiogênese por meio da regulação por espécies reativas de oxigênio (ROS). Entretanto, uma variante do gene do BDNF em humanos, o polimorfismo Val66Met (substituição do aminoácido valina por uma metionina na posição 66 do códon), que ocorre em 20-30% da população caucasiana, pode afetar as concentrações de BDNF no plasma e sua atividade em todos os tecidos periféricos contendo receptores tirosina quinase B (TrkB), como o endotélio. De fato, recentemente observamos que o polimorfismo Val66Met prejudica a reatividade vascular e o BDNF circulante em resposta ao treinamento físico. Dessa forma, apresentaremos a seguir uma discussão sobre os níveis séricos de BDNF na proteção cardiovascular, a variante genética Val66Met na reatividade vascular e o efeito do exercício físico.

Abstract Cardiovascular disease (CVD) is currently the leading cause of death in Brazil and worldwide. In 2016, CVD accounted for more than 17 million deaths, representing 31% of all deaths globally. Molecular and genetic mechanisms may be involved in vascular protection and should be considered in new therapeutic approaches. In this sense, recent studies have reported that brain-derived neurotrophic factor (BDNF) is reduced in individuals predisposed to develop CVD, and that aerobic physical training increases the amounts of circulating BDNF. BDNF is a neurotrophin found at high concentrations in the hippocampus and cerebral cortex and is considered a key molecule for the maintenance of synaptic plasticity and survival of neuronal cells. In addition to neuronal plasticity, BDNF is also important in vascular function, promoting angiogenesis through the regulation of reactive oxygen species (ROS). However, a variant of the BDNF gene in humans, the Val66Met polymorphism (substitution of the amino acid valine for a methionine at position 66 of the codon), occurring in 20-30% of the Caucasian population, may affect plasma BDNF concentrations and its activity in all peripheral tissues containing tyrosine kinase B receptors (TrkB), such as the endothelium. Thus, we will present a discussion about the role of serum BDNF levels in cardiovascular protection, Val66Met genetic variant in vascular reactivity and the effect of physical exercise.

Photobiomodulation by low-level laser therapy in patients with obstructive sleep apnea: Study protocol clinical trial (SPIRIT compliant).

Obstructive sleep apnea (OSA) increases morbidity and mortality and it is associated with an increased cardiovascular risk. The gold standard treatment for OSA is positive airway pressure therapy (CPAP). However, it is an expensive treatment and several patients do not adapt to CPAP. GOAL: The researchers will verify the effects of low-level laser therapy (LLLT) on OSA, when applied to the soft palate and on the tongue base. METHODS: The researchers will select individuals of both sexes aged 30 to 60 years old who are sedentary and that present a high risk of OSA by the Berlin questionnaire. The evaluations pre and post interventions will be polysomnography; anthropometric and body composition measurements (Bioimpedance); metabolic syndrome risk factors (International Diabetes Federation); physical capacity (VO2 peak at the cardiopulmonary exercise test, CPET); endothelial function (flow-mediated dilatation, FMD); autonomic control (heart rate variability and sympathovagal balance). Those diagnosed with moderate and severe OSA (apnea/hypopnea index, AHI ≥15 events/h) will be invited to participate in the study and they will be randomized into 2 groups: LLLT treatment or placebo (C). The LLLT group will receive applications at 8 points on the soft palate and on the base of the tongue for 8 seconds for each point. The applications of LLLT will occur twice a week, with a minimum interval of 2 days between the applications for 2 months, when using a Therapy Plus NS 13678 Laser. The C group will have similar applications, but with the device turned off. EXPECTED RESULTS: In the individuals with OSA, photobiomodulation through LLLT will decrease the AHI. Additionally, when LLLT is applied in the oral cavity, a highly vascularized region, this may cause improvements in the vascular function and in the autonomic and hemodynamic control. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committee of the Nove de Julho University, São Paulo, Brazil, on the date of March 11, 2019 (CAAE: 06025618.2.0000.5511 - Acceptance Number: 3.191.077). This trial has been registered with the Brazilian Registry of Clinical Trials (REBEC TRIAL RBR-42v548). This study is not yet recruiting. Issue date: November 4, 2019.

NK-lysin, dicentracin and hepcidin antimicrobial peptides in European sea bass. Ontogenetic development and modulation in juveniles by nodavirus.

Antimicrobial peptides (AMPs) are considered to be amongst the most powerful tools for the fight against pathogens in fish, since they form part of the innate immune response, which is especially vital in eggs and early larval stages, when the immune system is developing. The fish responsible for a large part of the profits in Mediterranean aquaculture is European sea bass (Dicentrarchus labrax), a species greatly susceptible to nodavirus (NNV), especially in the larval and juvenile stages. In this work, polyclonal antibodies were developed and used to detect and quantify NK-lysin, dicentracin and hepcidin AMPs in European sea bass eggs and during larval development, as well as to evaluate their regulation in juvenile specimens upon NNV infection. Basal and detectable levels of all the AMPs studied were present in eggs, confirming the maternal transfer of peptides, which increased in one or two waves during larval development up to 69 days post-fertilization. After NNV infection, the mRNA of all the AMPs analysed was up-regulated five days after infection in most of the tissues, whilst peptide quantification of all three AMPs decreased in the brain, the target tissue for NNV, but increased in the head-kidney 5 days after infection. Further research should be carried out to ascertain the role of AMPs in fish innate immunity and to understand how NNV evades the immune response to be disseminated.

Acute Ventilatory Support During Whole-Body Hybrid Rowing in Patients With High-Level Spinal Cord Injury: A Randomized Controlled Crossover Trial.

BACKGROUND: High-level spinal cord injury (SCI) results in profound spinal and supraspinal deficits, leading to substantial ventilatory limitations during whole-body hybrid functional electrical stimulation (FES)-rowing, a form of exercise that markedly increases the active muscle mass via electrically induced leg contractions. This study tested the effect of noninvasive ventilation (NIV) on ventilatory and aerobic capacities in SCI. METHODS: This blinded, randomized crossover study enrolled 19 patients with SCI (level of injury ranging from C4 to T8). All patients were familiar with FES-rowing and had plateaued in their training-related increases in aerobic capacity. Patients performed two FES-rowing peak exercise tests with NIV or without NIV (sham). RESULTS: NIV increased exercise tidal volume (peak, 1.50 ± 0.31 L vs 1.36 ± 0.34 L; P < .05) and reduced breathing frequency (peak, 35 ± 7 beats/min vs 38 ± 6 beats/min; P < .05) compared with the sham test, leading to no change in alveolar ventilation but a trend toward increased oxygen uptake efficiency (P = .06). In those who reached peak oxygen consumption (Vo2peak) criteria (n = 13), NIV failed to significantly increase Vo2peak (1.73 ± 0.66 L/min vs 1.78 ± 0.59 L/min); however, the range of responses revealed a correlation between changes in peak alveolar ventilation and Vo2peak (r = 0.89; P < .05). Furthermore, those with higher level injuries and shorter time since injury exhibited the greatest increases in Vo2peak. CONCLUSIONS: Acute NIV can successfully improve ventilatory efficiency during FES exercise in SCI but may not improve Vo2peak in all patients. Those who benefit most seem to be patients with cervical SCI within a shorter time since injury. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT02865343 and NCT03267212; URL: www.clinicaltrials.gov.

Identifying the risk of obstructive sleep apnea in metabolic syndrome patients: Diagnostic accuracy of the Berlin Questionnaire.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor frequently present in patients with metabolic syndrome (MetS). Additionally, moderate and severe OSA are highly prevalent in patients with cardiac disease, as they increase the riskfor cardiovascular events by 80%. The gold standard diagnostic method for OSA is overnight polysomnography (PSG), which remains unaffordable for the overall population. The aim of the present study was to evaluate whether the Berlin Questionnaire (BQ) is anuseful tool for assessing the risk of OSA in patients with MetS. METHODS: 97 patients, previously untreated and recently diagnosed with MetS (National Cholesterol Education Program, Adult Treatment Panel III, ATP-III) underwent a PSG. OSA was characterized by the apnea-hypopnea index (AHI). BQ was administered before PSG and we evaluated sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS: Of the 97 patients with MetS, 81 patients had OSA, with 47 (48.5%) presenting moderate and severe OSA. For all MetS with OSA (AHI≥5 events/hour), the BQ showed good sensitivity (0.65, 95% CI 0.54 to 0.76) and fair specificity (0.38, 95% CI 0.15-0.65) with a positive predictive value of 0.84, a negative predictive value of 0.18 and an 84% accuracy. Similarly, for moderate-to-severe OSA (AHI≥15 events/hour) we found good sensitivity (0.73, 95% CI 0.58-0.85) and fair specificity (0.40, 95% CI 0.27-0.55). Interestingly, for severe OSA (AHI≥30 events/hour), there was a very good sensitivity (0.91, 95% CI 0.72-0.99) and moderate specificity (0.42, 95% CI 0.31-0.54). CONCLUSION: The BQ is a valid tool for screening the risk of OSA in MetS patients in general, and it is particularly useful in predicting severe OSA.

Does obstructive sleep apnea affect exercise capacity and the hemodynamic response to exercise? An individual patient data and aggregate meta-analysis.

Obstructive sleep apnea (OSA) has been linked to altered cardiovascular response to exercise. A systematic review and individual patient data (IPD) meta-analysis were conducted to assess whether OSA patients present reduced exercise capacity. PubMed, Embase and Web of Science were searched until September 2018. Studies which performed sleep recording in both OSA patients and controls and measured maximal oxygen consumption (VO2peak) via a maximal exercise test were included. IPD were provided for five trials upon the 18 eligible (N = 289) and a two-stage IPD meta-analysis model was used, allowing to standardize the apnea cutoff and adjust for confounders. IPD meta-analysis demonstrated that moderate to severe OSA patients had similar VO2peak (mean difference: -1.03 mL·kg-1 min-1; 95% CI: -3.82 to 1.76; p = 0.47) and cardiovascular response to exercise compared to mild or non-OSA patients. By contrast, aggregate data (AD) meta-analysis including the 13 trials for which IPD were unavailable (N = 605) revealed that VO2peak was reduced in OSA patients compared to controls (mean difference: -2.30 mL·kg-1 min-1; 95% CI: -3.96 to -0.63; p < 0.001) with high heterogeneity. In conclusion, IPD meta-analysis suggests that VO2peak and the cardiovascular response to exercise are preserved in moderate to severe OSA patients while AD meta-analysis suggests lower VO2peak in severe OSA.

Diet associated with exercise improves baroreflex control of sympathetic nerve activity in metabolic syndrome and sleep apnea patients.

PURPOSE: We tested the hypothesis that (i) diet associated with exercise would improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients with and without obstructive sleep apnea (OSA) and (ii) the effects of this intervention would be more pronounced in patients with OSA. METHODS: Forty-six MetS patients without (noOSA) and with OSA (apnea-hypopnea index, AHI > 15 events/h) were allocated to no treatment (control, C) or hypocaloric diet (- 500 kcal/day) associated with exercise (40 min, bicycle exercise, 3 times/week) for 4 months (treatment, T), resulting in four groups: noOSA-C (n = 10), OSA-C (n = 12), noOSA-T (n = 13), and OSA-T (n = 11). Muscle sympathetic nerve activity (MSNA), beat-to-beat BP, and spontaneous arterial baroreflex function of MSNA (ABRMSNA, gain and time delay) were assessed at study entry and end. RESULTS: No significant changes occurred in C groups. In contrast, treatment in both patients with and without OSA led to a significant decrease in weight (P < 0.05) and the number of MetS factors (P = 0.03). AHI declined only in the OSA-T group (31 ± 5 to 17 ± 4 events/h, P < 0.05). Systolic BP decreased in both treatment groups, and diastolic BP decreased significantly only in the noOSA-T group. Treatment decreased MSNA in both groups. Compared with baseline, ABRMSNA gain increased in both OSA-T (13 ± 1 vs. 24 ± 2 a.u./mmHg, P = 0.01) and noOSA-T (27 ± 3 vs. 37 ± 3 a.u./mmHg, P = 0.03) groups. The time delay of ABRMSNA was reduced only in the OSA-T group (4.1 ± 0.2 s vs. 2.8 ± 0.3 s, P = 0.04). CONCLUSIONS: Diet associated with exercise improves baroreflex control of sympathetic nerve activity and MetS components in patients with MetS regardless of OSA.

Inconsistent relation of nonlinear heart rate variability indices to increasing vagal tone in healthy humans.

BACKGROUND: Prior work has found that linear heart rate variability (HRV) indices do not accurately reflect cardiac vagal control, and nonlinear indices of HRV have been proposed as alternative tools that may better capture cardiac vagal effects. We used progressive low dose atropine to induce changes in cardiac vagal tone to test the hypotheses that nonlinear HRV indices accurately reflect cardiac vagal control, and that their changes in response to low dose atropine correlate with those in RR interval. METHODS: Changes in RR interval and HRV indices during intravenous injections of saline (control) and 6 cumulative doses of atropine (from 1.4 to 7.2 µg/kg) during controlled breathing at 15 breaths per minute were assessed in 14 young healthy individuals. RESULTS: As expected, low dose atropine increased average RR interval (vagotonic effect). There was no strong association between vagotonic changes in RR interval and the majority of nonlinear HRV indices, either within or among subjects. CONCLUSIONS: These data suggest an inconsistent relationship between responses of nonlinear HRV indices and RR interval to changes in cardiac vagal tone. Therefore, nonlinear HRV indices may not be reliable indices of cardiac vagal control in healthy humans.

Arterial stiffness and its association with clustering of metabolic syndrome risk factors.

BACKGROUND: Metabolic syndrome (MetS) is associated with structural and functional vascular abnormalities, which may lead to increased arterial stiffness, more frequent cardiovascular events and higher mortality. However, the role played by clustering of risk factors and the combining pattern of MetS risk factors and their association with the arterial stiffness have yet to be fully understood. Age, hypertension and diabetes mellitus seem to be strongly associated with increased pulse wave velocity (PWV). This study aimed at determining the clustering and combining pattern of MetS risk factors and their association with the arterial stiffness in non-diabetic and non-hypertensive patients. METHODS: Recently diagnosed and untreated patients with MetS (n = 64, 49 ± 8 year, 32 ± 4 kg/m2) were selected, according to ATP III criteria and compared to a control group (Control, n = 17, 49 ± 6 year, 27 ± 2 kg/m2). Arterial stiffness was evaluated by PWV in the carotid-femoral segment. Patients were categorized and analyzed according MetS risk factors clustering (3, 4 and 5 factors) and its combinations. RESULTS: Patients with MetS had increased PWV when compared to Control (7.8 ± 1.1 vs. 7.0 ± 0.5 m/s, p < 0.001). In multivariate analysis, the variables that remained as predictors of PWV were age (ß = 0.450, p < 0.001), systolic blood pressure (ß = 0.211, p = 0.023) and triglycerides (ß = 0.212, p = 0.037). The increased number of risk factors reflected in a progressive increase in PWV. When adjusted to systolic blood pressure, PWV was greater in the group with 5 risk factors when compared to the group with 3 risk factors and Control (8.5 ± 0.4 vs. 7.5 ± 0.2, p = 0.011 and 7.2 ± 0.3 m/s, p = 0.012). Similarly, the 4 risk factors group had higher PWV than the Control (7.9 ± 0.2 vs. 7.2 ± 0.3, p = 0.047). CONCLUSIONS: The number of risk factors seems to increase arterial stiffness. Notably, besides age and increased systolic blood pressure, alterations in the triglycerides worsened the stiffness of large vessels, emphasizing the importance in addressing this risk factor in MetS patients.

The role of increased glucose on neurovascular dysfunction in patients with the metabolic syndrome.

Metabolic syndrome (MetS) causes autonomic alteration and vascular dysfunction. The authors investigated whether impaired fasting glucose (IFG) is the main cause of vascular dysfunction via elevated sympathetic tone in nondiabetic patients with MetS. Pulse wave velocity, muscle sympathetic nerve activity (MSNA), and forearm vascular resistance was measured in patients with MetS divided according to fasting glucose levels: (1) MetS+IFG (blood glucose ≥100 mg/dL) and (2) MetS-IFG (<100 mg/dL) compared with healthy controls. Patients with MetS+IFG had higher pulse wave velocity than patients with MetS-IFG and controls (median 8.0 [interquartile range, 7.2-8.6], 7.3 [interquartile range, 6.9-7.9], and 6.9 [interquartile range, 6.6-7.2] m/s, P=.001). Patients with MetS+IFG had higher MSNA than patients with MetS-IFG and controls, and patients with MetS-IFG had higher MSNA than controls (31±1, 26±1, and 19±1 bursts per minute; P<.001). Patients with MetS+IFG were similar to patients with MetS-IFG but had higher forearm vascular resistance than controls (P=.008). IFG was the only predictor variable of MSNA. MSNA was associated with pulse wave velocity (R=.39, P=.002) and forearm vascular resistance (R=.30, P=.034). In patients with MetS, increased plasma glucose levels leads to an adrenergic burden that can explain vascular dysfunction.

Prevalence and severity of syndrome Z in women with metabolic syndrome on waiting list for bariatric surgery: a cross-sectional study.

BACKGROUND: In recent years, obesity has become one of the most important public health problems in the world, with a growing prevalence in both developed and developing countries. Recent studies show that sleep disturbances, especially obstructive sleep apnoea (OSA) may be a manifestation of metabolic syndrome (MetS). Although the association of OSA with the MetS is largely attributed to obesity, the exact pathophysiological mechanisms and their individual characteristics still need to be identified. This study investigated the prevalence and severity of syndrome Z in obese women with MetS on waiting list for bariatric surgery. METHODS: In this double-center cross-sectional study, female patients aged ≥18 years, stage III severe obesity with MetS, on waiting list for bariatric surgery were recruited. The diagnosis for MetS was made according to the criteria of the national cholesterol education program, adult treatment panel III. Clinical, anthropometric, demographic, biochemistry, and sleep measurements were collected. Correlations between continuous variables with sleep parameters were performed using the Pearson correlation test or Spearman correlation test. RESULTS: The mean age of 83 patients was 44.8 ± 11.2 years and mean BMI was 42.6 ± 8.1 kg/m2. There was a significant correlation between OSA and metabolic score (r = 0.336; P = 0.002), neck circumference (r = 0.218; P = 0.048), basal systolic blood pressure (r = 0.280; P = 0.01), total cholesterol (r = 0.277; P = 0.011) and abdomen circumference (r = 0.284; P = 0.009). The mean values of excessive daytime sleepiness were 10.5 ± 7 demonstrating a value considered normal for its presence. However, a high risk for OSA was observed in practically the entire population. It was observed that the prevalence of Syndrome Z (75.9%) increased significantly according to apnoea hypopnoea index (AHI) (P for trend <0.0000). A prevalence of 27.71% for mild OSA, 20.48% for moderate OSA, and 27.71% for severe OSA was observed. An association of AHI severity with all components of MetS was also observed. CONCLUSIONS: We can conclude that syndrome Z presents a high prevalence in a female population with MetS and a considerable severity according to the presence of OSA. Therefore, patients with MetS should be investigated for the presence of sleep disorders. Trial registration The study has been registered on ClinicalTrials.gov NCT02409160 and followed the standards of The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies.

Insights into the diversity of NOD-like receptors: Identification and expression analysis of NLRC3, NLRC5 and NLRX1 in rainbow trout.

Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are efficient soluble intracellular sensors that activate defense mechanisms against pathogens. In teleost fish, the involvement of NLRs in the immune response is not well understood. However, recent work has evidenced the expression of different NLRs in response to some pathogen associated molecular patterns (PAMPs). In the present work, the cDNA sequence encoding three new NOD-like receptors were identified in Oncorhynchus mykiss, namely OmNLRC3, OmNLRC5 and OmNLRX1. Results showed that their sequences coded for proteins of 1135, 836 and 1010 amino acids, respectively. The deduced protein sequences of all receptors showed characteristic domains of this receptor family, such as leucine rich repeats and NACHT domain. Phylogenetic analysis revealed a high degree of identity with other NOD-like receptors and they are clustered into different families. Transcript expression analysis indicated that OmNLRs are constitutively expressed in liver, spleen, intestine, gill, skin and brain. OmNLR expression was upregulated in kidney and gills from rainbow trout in response to LPS. In order to give new insights into the function of these new NLR members, an in vitro model of immune stimulation was established using the rainbow trout cell line RTgill-W1. Expression analysis revealed that RTgill-W1 overexpressed proinflammatory cytokines in response to LPS and poly I:C alongside with a differential overexpression of OmNLRC3, OmNLRC5 and OmNLRX1. The expression of OmNLRC5 was further verified at the protein level by immunofluorescence. Finally, the effect of the overexpressed cytokines on the OmNLR expression by RTgill-W1 cells was assessed, suggesting a regulatory mechanism on OmNLRC3 expression. Overall, results suggest that O. mykiss NOD-like receptors could play a key role in the defense mechanisms of teleost through PAMP recognition. Future studies will focus on gills which could be related with a key sensor mucosal system in one of the most environmentally fish exposed tissues.

The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects.

Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX-reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2 saturation and PMNs RLU (R = -0.62, P = 0.02), and with LF/HF (R = -0.79, P = 0.02) post-HPX6. In addition, an association was found between PMNs RLU and PR post-HPX6 (R = 0.58, P = 0.04). Conclusion: Acute exposure to intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may lead to an impairment in peripheral vascular resistance.