The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up

Genetic risk factors of Alzheimer’s Disease disrupt resting-state functional connectivity in cognitively intact young individuals

Background Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer’s Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition. Methods We investigated the effects of genetic risk factors of AD, namely APOEe4 and MAPTA alleles, on resting-state functional connectivity in a cohort of 129 cognitively intact young adults (aged 17–22 years). We used Independent Component Analysis to identify networks of interest, and Gaussian Random Field Theory to compare connectivity between groups. Seed-based analysis was used to quantify inter-regional connectivity strength from the clusters that exhibited significant between-group differences. To investigate the relationship with cognition, we correlated the connectivity and the performance on the Stroop task. Results The analysis revealed a decrease in functional connectivity in the Default Mode Network (DMN) in both APOEe4 carriers and MAPTA carriers in comparison with non-carriers. APOEe4 carriers showed decreased connectivity in the right angular gyrus (size = 246, p-FDR = 0.0079), which was correlated with poorer performance on the Stroop task. MAPTA carriers showed decreased connectivity in the left middle temporal gyrus (size = 546, p-FDR = 0.0001). In addition, we found that only MAPTA carriers had a decreased connectivity between the DMN and multiple other brain regions. Conclusions Our findings indicate that APOEe4 and MAPTA alleles modulate brain functional connectivity in the brain regions within the DMN in cognitively intact young adults. APOEe4 carriers also showed a link between connectivity and cognition

An Exploration of Methods to Resolve Inconsistent Self-Reporting of Chronic Conditions and Impact on Multimorbidity in the Canadian Longitudinal Study on Aging

OBJECTIVES: To quantify inconsistent self-reporting of chronic conditions between the baseline (2011-2015) and first follow-up surveys (2015-2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity.METHODS: Community-dwelling adults aged 45-85 years in the baseline and first follow-up surveys were included ( n = 45,184). At each survey, participants self-reported whether they ever had a physician diagnosis of 35 chronic conditions. Identifiable inconsistent responses were enumerated. RESULTS: 32-40% of participants had at least one inconsistent response across all conditions. Illness-related information (e.g., taking medication) resolved most inconsistent responses (&gt;93%) while computer-assisted software asking participants to confirm their inconsistent disease status resolved ≤53%. Using these adjudication methods, multimorbidity prevalence at follow-up increased by ≤1.6% compared to the prevalence without resolving inconsistent responses.DISCUSSION: Inconsistent self-reporting of chronic conditions is common but may not substantially affect multimorbidity prevalence. Future research should validate methods to resolve inconsistencies.</p

Levantamento epidemiológico retrospectivo de sepse na unidade de terapia intensiva do Hospital Universitário Lauro Wanderley / Retrospective epidemiological survey of sepsis in the intensive care unit of Lauro Wanderley University Hospital

A sepse é considerada a principal causa de morte em pacientes internados em Unidades de Terapia Intensiva e este quadro pouco tem evoluído, apesar dos desenvolvimentos obtidos na área. Este estudo objetivou determinar o perfil epidemiológico e as características dos pacientes com sepse, internados na UTI adulto do Hospital Universitário Lauro Wanderley, na Paraíba. Trata-se de um estudo retrospectivo, observacional, que avaliou o perfil epidemiológico e características dos pacientes com sepse que foram internados na UTI adulto do Hospital Universitário Lauro Wanderley, no período entre janeiro de 2013 a dezembro de 2017. Os dados estudados foram provenientes dos registros de infecção hospitalar, os quais foram preenchidos e analisados pela equipe multiprofissional da Comissão de Controle de Infecção Hospitalar (CCIH) do HULW. A análise estatística descritiva dos resultados foi realizada por meio das frequências absolutas e relativas para as variáveis categóricas; e da média e desvio padrão ou mediana, para as variáveis contínuas. De um total de 2211 prontuários, foram incluídos 297, os quais foram classificados com sepse (68,4 %) ou choque séptico (31,6 %). Houve predominância de pacientes do sexo masculino (52,5%) e faixa etária maior de 70 anos (39,7%). A média de tempo de internação foi de 16,8 dias. As principais fontes de infecção foram pulmão (17%) e trato urinário (9%). Entre as comorbidades dos pacientes admitidos, complicações renais (20%) e complicações respiratórias (15%) foram as mais frequentes. Quanto às hemoculturas realizadas e computadas, os principais agentes etiológicos foram bacilos Gram negativos (62%). A mortalidade na sepse e no choque séptico foi de 47,1% e 66,2%, respectivamente. O estudo evidenciou que a sepse acometeu, em sua maioria, idosos do sexo masculino, sendo o principal foco infecioso de origem pulmonar. Constataram-se ainda elevadas taxas de mortalidade, principalmente em casos de choque séptico

High Energy Physics in the Atmosphere: Phenomenology of Cosmic Ray Air Showers

The properties of cosmic rays with energies above 10**6 GeV have to be deduced from the spacetime structure and particle content of the air showers which they initiate. In this review we summarize the phenomenology of these giant air showers. We describe the hadronic interaction models used to extrapolate results from collider data to ultra high energies, and discuss the prospects for insights into forward physics at the LHC. We also describe the main electromagnetic processes that govern the longitudinal shower evolution, as well as the lateral spread of particles. Armed with these two principal shower ingredients and motivation from the underlying physics, we provide an overview of some of the different methods proposed to distinguish primary species. The properties of neutrino interactions and the potential of forthcoming experiments to isolate deeply penetrating showers from baryonic cascades are also discussed. We finally venture into a terra incognita endowed with TeV-scale gravity and explore anomalous neutrino-induced showers.Comment: Typo in caption of Fig. 8 corrected, references adde

Comprehensive allostatic load risk index is associated with increased frontal and left parietal white matter hyperintensities in mid-life cognitively healthy adults

To date, there is a considerable heterogeneity of methods to score Allostatic Load (AL). Here we propose a comprehensive algorithm (ALCS) that integrates commonly used approaches to generate AL risk categories and assess associations to brain structure deterioration. In a cohort of cognitively normal mid-life adults (n = 620, age 51.3 ± 5.48 years), we developed a comprehensive composite for AL scoring incorporating gender and age differences, high quartile approach, clinical reference values, and current medications, to then generate AL risk categories. Compared to the empirical approach (ALES), ALCS showed better model fit criteria and a strong association with age and sex. ALSC categories were regressed against brain and white matter hyperintensity (WMH) volumes. Higher AL risk categories were associated with increased total, periventricular, frontal, and left parietal WMH volumes, also showing better fit compared to ALES. When cardiovascular biomarkers were removed from the ALSC algorithm, only left-frontal WMHV remained associated with AL, revealing a strong vascular burden influencing the index. Our results agree with previous evidence and suggest that sustained stress exposure enhances brain deterioration in mid-life adults. Showing better fit than ALES, our comprehensive algorithm can provide a more accurate AL estimation to explore how stress exposure enhances age-related health decline.</p

Salivary gland tumors : a 13-year clinicopathologic retrospective study in a Brazilian northeast population

The present study aimed to evaluate the clinicopathologic features of salivary gland tumors (SGTs) in a Brazillian northeast population. A retrospective descriptive cross-sectional study was performed (1995-2009). All cases of SGTs diagnosed in a priva