Human longevity is associated with regular sleep patterns, maintenance of slow wave sleep, and favorable lipid profile

Some individuals are able to successfully reach very old ages, reflecting higher adaptation against age-associated effects. Sleep is one of the processes deeply affected by aging; however few studies evaluating sleep in long-lived individuals (aged over 85) have been reported to date. the aim of this study was to characterize the sleep patterns and biochemical profile of oldest old individuals (N = 10, age 85-105 years old) and compare them to young adults (N = 15, age 20-30 years old) and older adults (N = 13, age 60-70 years old). All subjects underwent full-night polysomnography, 1-week of actigraphic recording and peripheral blood collection. Sleep electroencephalogram spectral analysis was also performed. the oldest old individuals showed lower sleep efficiency and REM sleep when compared to the older adults, while stage N3 percentage and delta power were similar across the groups. Oldest old individuals maintained strictly regular sleep-wake schedules and also presented higher HDL-cholesterol and lower triglyceride levels than older adults. the present study revealed novel data regarding specific sleep patterns and maintenance of slow wave sleep in the oldest old group. Taken together with the favorable lipid profile, these results contribute with evidence to the importance of sleep and lipid metabolism regulation in the maintenance of longevity in humans.Associacao Fundo de Incentivo a Pesquisa (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Geriatria & Gerontol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent Med, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Geriatria & Gerontol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent Med, BR-04024002 São Paulo, BrazilFAPESP: 11/18976-9Web of Scienc

A Single-Center, Retrospective Comparison of Non-Pre-emptive with Pre-emptive Renal Transplantations

Introduction. End-stage renal disease (ESRD) requires renal replacement therapy, either through pre-emptive transplantation (PET) or non-pre-emptive transplantation (non-PET). PET is associated with improved patient and allograft survival compared to non-PET; however, only 2.5% of patients in the United States undergo PET. The authors of this study report on mortality and allograft rejection rates in patients undergoing PET versus non-PET. Methods. This single-center, retrospective study compared post-transplant complications between PET and non-PET in adults with ESRD. De-identified electronic health record data from 2017 to 2022 were analyzed. Odds ratios (ORs) for one-year post-transplant mortality and allograft rejection were calculated using unadjusted multivariate logistic regression (Model 1), adjusted for age and sex (Model 2), and further adjusted for comorbidities (Model 3). Results. Of 787 patients with ESRD who underwent kidney transplantation, 14% of patients experienced PTD and 86% experienced PET. Comparing PTD to PET, the OR for 1-year-postoperative mortality in Model 1 was 1.76 (95%CI 0.64-4.85; p=0.27), in Model 2 was 2.02 (95%CI 0.71-5.71; p=0.19) and in Model 3 was 1.86 (95%CI 0.64-5.39; p=0.24). Comparing PTD to PET, the ORs for 1-year postoperative transplant rejection in Model 1 was 1.63 (95%CI 0.85-3.10; p=0.13), in Model 2 was 1.61 (95%CI 0.84 -3.06; p=0.15) and in Model 3 was 1.60 (95%CI 0.82-3.10; p=0.16).  Conclusions. This single-center investigation found no significant difference between the renal replacement therapy options for ESRD

Epidemiological, physiological and genetic aspects of sleep in the well-succeeded aging

O aumento da expectativa de vida nas ultimas decadas indica que o envelhecimento populacional no Brasil e no mundo seja inevitavel. Neste contexto, existem individuos capazes de alcancar com sucesso idades avancadas, indicando maior adaptacao as alteracoes decorrentes do envelhecimento. Sabe-se que o sono e um processo profundamente afetado pelo envelhecimento, no entanto o papel do sono na manutencao da longevidade em humanos ainda e desconhecido. O presente estudo teve como objetivo caracterizar os aspectos epidemiologicos, fisiologicos e geneticos do sono no envelhecimento bem-sucedido por meio da conducao de tres investigacoes: 1) Estudo da prevalencia e fatores associados a queixas de sono em populacoes de idosos acima de 65 anos em paises em desenvolvimento; 2) Avaliacao do padrao de sono, do perfil bioquimico, hormonal e oxidativo, da expressao genica e de sua regulacao entre individuos Jovens, Idosos e Longevos; e 3) Investigacao de polimorfismos geneticos e variantes raras e associacao com o envelhecimento bem-sucedido. Em relacao ao primeiro estudo, foi possivel descrever que a prevalencia das queixas de sono variou de 9,1 a 37,7% nos paises estudados e os principais fatores associados foram pertencer ao sexo feminino, apresentar residencia urbana, possuir menor nivel educacional, praticar menos atividades fisicas, apresentar pior estado de Saúde e maior numero de comorbidades. O segundo estudo revelou que, em relacao ao padrao de sono, Longevos (acima de 85 anos de idade) nao apresentaram reducao significativa da porcentagem de estagio N3, e da potencia espectral de delta neste estagio de sono, indicando a manutencao do sono de ondas lentas na longevidade. Longevos tambem apresentaram padroes de sono estritamente regulares em relacao aos Idosos (de 60 a 70 anos) ou Jovens (de 20 a 30 anos). Melhor perfil lipidico foi identificado em Longevos quando comparados aos Idosos, sugerindo sua participacao sobre diversos aspectos fisiologicos que favorecem o alcance de idades avancadas. Foram identificados nove genes diferencialmente expressos entre os grupos estudados, com especial atencao ao gene SIRT2 e CCL5, que apresentaram evidencias de regulacao epigenetica com a longevidade. O terceiro estudo contou com a analise de variantes geneticas e detectou a associacao entre os polimorfismos rs10405150, rs10410544 e rs4802998 do gene SIRT2 e a longevidade em uma amostra expandida da populacao. Alem disso, o sequenciamento do genoma completo revelou variantes possivelmente envolvidas no fenotipo da longevidade nos genes diferencialmente expressos. O presente estudo permitiu a caracterizacao detalhada de diversos aspectos relacionados ao envelhecimento bem-sucedido e a longevidade e aponta para a existencia de mecanismos moleculares comuns entre o sono, o metabolismo lipidico e a longevidade em humanos, possivelmente mediados pelo gene SIRT2 e suas vias de regulacao. Assim, a identificacao destes mecanismos pode contribuir para o desenvolvimento de ferramentas clinicas que propiciem a populacao idosa uma melhor qualidade de vidaThe increase in life expectancy in the last decades indicates that aging at the population level is unavoidable. In this sense, some individuals are able to successfully reach very old ages, reflecting higher adaptation against the age-related effects. Sleep is one of the processes deeply affected by aging; however the role of sleep in the maintenance of longevity in humans is still unknown. This study aimed to characterize the epidemiological, physiological and genetic aspects of sleep in wellsucceeded aging by three investigations: 1) Study of the prevalene and correlates of sleep complaints in elderly populations over 65 years old in low and middle income countries; 2) Evaluation of sleep patterns, biochemical, hormonal and oxidative profile, as well as gene expression and its regulation among young adults, older adults and oldest old individuals; and 3) Investigation of genetic polymorphism and rare variants and association with well-succeeded aging. Regarding the first study, we described that the prevalence of sleep complaints varied from 9.1% to 37.7% in the studied countries, and female gender, urban residence, low educational level, low physical activity status, poor health and high number of co-morbidities were associated with sleep complaints. The second study revealed that, regarding the sleep patterns, oldest old individuals (over 85 years old) did not show significant reduction in stage N3 or in delta spectral power in this sleep stage, indicating the maintenance of slow wave sleep in the longevity. Oldest old individuals also showed strictly regular sleep wake schedules than young adults (20 to 30 years old) and better lipid profile than older adults (60 to 70 years old), suggesting that these mechanisms might be related to reaching older ages. We identified nine differentially expressed genes among the studied groups, being SIRT2 and CCL5 the most relevant, since their expression has also been related to epigenetic mechanisms. The third study detected that three single nucleotide polymorphisms located on SIRT2 gene (rs10405150, rs10410544, and rs4802998) were associated with longevity in the genetic association study. Moreover, rare variants potentially associated with longevity in the differentially expressed genes were also described as a result of the whole genome sequencing. The present study allowed the detailed characterization of aspects related to well-succeeded aging and longevity, and suggests the existence of common molecular mechanisms integrating sleep, lipid metabolism and longevity in humans, possibly mediated through the expression of SIRT2 gene and its regulatory pathways. The identification of such mechanisms might contribute to the development of clinical tools that provide a better quality of life to the elderly population.Associação Fundo de Incentivo à Psicofarmacologia (AFIP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)BV UNIFESP: Teses e dissertaçõe

The role inflammatory response genes in obstructive sleep apnea syndrome: a review

Obstructive sleep apnea syndrome (OSAS) has a negative impact on health and behavior of millions of individuals worldwide. The pathogenesis of this disorder is a multifactorial process related to a variety of mechanisms, including selective activation of inflammatory response pathways. A number of inflammatory factors, such as IL-6, IL-8, and TNF-alpha, can be found in high concentrations in subjects with OSAS and may serve as biological markers of this disease. The concentration of these cytokines contributes to weight gain in patients with OSAS and can also modify the risk of obesity-related metabolic disorders, especially insulin resistance. Nevertheless, the mechanisms by which specific genes are associated with these processes are still poorly known. In addition to gene expression studies, investigations aiming at the identification of epigenetic factors associated with OSAS are still scarce in the literature. The documented data support the hypothesis that the molecular changes that mediate inflammatory response are important mechanisms in the pathogenesis of OSAS, sleepiness, insulin resistance, visceral obesity, and cardiovascular disease, perhaps by leading to a more severe OSAS. Often, systemic changes may not be detected in mild OSA; however, molecular changes, which are much more sensitive to the mechanisms of intermittent hypoxia and oxidative stress, may be present. This review aimed to show an updated view on the studies evaluating the genetic basis of inflammatory response in many aspects of OSAS and to highlight potential research areas not fully explored to date in this field.Associacao Fundo de Incentivo a Pesquisa (AFIP)Fundacao de Amparo a Pesquisa do Estado de Sao PauloCoordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Fed Sao Paulo, Dept Psicobiol, Rua Napoleao Barros,925 Vila Clementino, BR-04024002 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Rua Napoleao Barros,925 Vila Clementino, BR-04024002 Sao Paulo, SP, BrazilWeb of Scienc

Association Between Uric Acid Levels and Obstructive Sleep Apnea Syndrome in a Large Epidemiological Sample

Introduction: Recurrent hypoxia, which is associated with obstructive sleep apnea syndrome (OSAS), leads to an increase in the degradation of adenosine triphosphatase into xanthine, which in turn increases uric acid concentrations.Objective: the current study aimed to determine whether an association exists between OSAS and uric acid levels in the peripheral blood from a representative population of São Paulo (Brazil).Methods: A population-based survey adopting a probabilistic 3-stage cluster sample of São Paulo was used to represent the population according to gender, age, and socioeconomic class. A total of 1,042 volunteers underwent polysomnography recordings for OSAS diagnosis, blood pressure assessment, and biochemical blood analysis, and answered questionnaires.Results: Uric acid levels were correlated with most important risk factors for OSAS, such as AHI, desaturation time and index, minimum oxyhemoglobin saturation (SpO(2)), blood pressure, cholesterol, BMI, triglycerides and arousal, and with OSAS itself. Also, uric acid was increased in OSAS volunteers even after controlling for all confounders. Hyperuricemic volunteers presented lower mean and minimum SpO(2) and increased desaturation index. Importantly, minimum SpO(2) was a significant predictor of uric acid levels, which in turn was considered an independent predictor for OSAS in the binary logistic model. However, a ROC curve analysis for establishing cut-off points for uric acid levels as a biomarker of OSAS revealed moderate sensitivity and specificity.Conclusion: A strong association was found between uric acid levels and OSAS in a representative sample of the population of São Paulo. Although they do not qualify for a biomarker alone, uric acid levels may be involved in OSAS severity and should be considered in sleep apnea management in the future.Associacao Fundo de Incentivo a Pesquisa (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilFAPESP: CEPID 98/14303-3FAPESP: 10/50129-1Web of Scienc

Loop Gain as a Predictor of Blood Pressure Response in Patients Treated for Obstructive Sleep Apnea: Secondary Analysis of a Clinical Trial.

Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain (ventilatory instability), which may thus herald cardiovascular treatment benefit. Objectives: To test the hypothesis that loop gain predicts changes in 24-hour mean blood pressure (MBP) in response to OSA therapy and compare its predictive value against that of other novel biomarkers. Methods: The HeartBEAT (Heart Biomarker Evaluation in Apnea Treatment) trial assessed the effect of 12 weeks of continuous positive airway pressure (CPAP) versus oxygen versus control on 24-hour MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24-h MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arms, respectively. Overall, changes in 24-hour MBP were small, but interindividual variability was substantial (mean [standard deviation], -2 [8] and 1 [8] mm Hg in the CPAP and oxygen arms, respectively). Higher loop gain was significantly associated with greater reductions in 24-hour MBP independent of covariates in the CPAP arm (-1.5 to -1.9 mm Hg per 1-standard-deviation increase in loop gain; P ⩽ 0.03) but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT01086800)

The effect of the severity of obstructive sleep apnea syndrome on telomere length

Aging is associated with an increase in the prevalence of obstructive sleep apnea syndrome (OSAS) as well as the shortening of telomeres. It is known that OSAS-related factors are stimuli that can contribute to the acceleration of cellular senescence. Thus, the present study aimed to compare the leukocyte telomere length (LTL) between OSAS patients and controls, as well as to verify the correlation between LTL and sleep parameters. We used DNA extracted of 928 individuals from EPISONO to measure the LTL by the quantitative real-time polymerase chain reaction. All individuals were subjected to one full-night polysomnography. LTL was significantly shorter in OSAS patients compared to controls. The results showed negative correlations between LTL and the following variables: apnea-hypopnea index, respiratory disturbance index, desaturation index and wake after sleep onset. LTL was positively correlated with sleep efficiency, total sleep time, basal, minimum and maximum oxygen saturation. Lastly, it was observed that OSAS severity was associated with shorter LTL even after adjusting for sex, age, years of schooling, body mass index, diabetes, stroke and heart attack. In conclusion, our study indicates the presence of an association between LTL and OSAS and a significant impact of severity of OSAS in telomeres shortening.Associação Fundo de Incentivo à Psicofarmacologia (AFIP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed Sao Paulo, Dept Psicobiol, UNIFESP, Sao Paulo, BrazilUniv Fed Sao Paulo, LINC, UNIFESP, Sao Paulo, BrazilUniv Tubingen, Dept Psychiat, Tubingen, GermanyUniv Fed Sao Paulo, UNIFESP, Grp Pesquisa Neurociencia Comportamental & Mol Tr, Sao Paulo, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Morfol & Genet, Sao Paulo, BrazilAmity Univ Uttar Pradesh, Amity Inst Biotechnol, Noida, IndiaDepartamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrasilLaboratório Interdisciplinar de Neurociências Clínicas (LINC), Universidade Federal de São Paulo (UNIFESP), São Paulo, BrasilGrupo de Pesquisa em Neurociência Comportamental e Molecular do Transtorno Bipolar, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrasilDepartamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrasilFAPESP: 2014/15259-2FAPESP: 2015/17549-0Web of Scienc

Contribuições dos sistemas de informações no gerenciamento de riscos hospitalares:: revisão integrativa da literatura

O objetivo deste estudo foi identificar as contribuições dos sistemas de informações hospitalares para o gerenciamento de riscos em saúde e em enfermagem. Trata-se de uma revisão integrativa da literatura na SciELO e nas Bases de Dados LILACS, Medline, de 2004 a 2014, utilizando os descritores hospital, information, system, nursing, management, risk e safety. Foram identificadas 10 pesquisas que apontam as contribuições e fatores que influenciam a aplicação de Sistemas de Informação Hospitalares para o Gerenciamento de Riscos em Saúde e Enfermagem, com ênfase para os aspectos sociotécnicos e abordagens que favoreçam a cultura de segurança institucional integrada a políticas preventivas e corretivas no nível técnico, individual, institucional, social, nacional e internacional. O profissional da enfermagem possui grande envolvimento no atendimento do paciente, sendo assim o objetivo da implementação do sistema de informação deve estar conectado com o objetivo da enfermagem para garantir a adesão e sua aplicação de maneira adequada. Identificou-se potencialidades e barreiras no uso do sistema de informação no gerenciamento, a superação destas barreiras requer investimentos estruturais e processuais

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype* group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilFMABC, Dept Saude Colet, Santo Andre, SP, BrazilUniv Fed Sao Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Morfol & Genet, Disciplina Genet, Sao Paulo, SP, BrazilCtr Univ Fundcao Inst Ensino Osasco UNIFIEO, Dept Psicol Educ, Osasco, SP, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Interdisciplinar Neurociencias Clin LiNC, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Morfol & Genet, Disciplina Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, SP, BrazilFAPESP: 2007/58736-1FAPESP: 2011/50740-5Web of Scienc