Phenotyping Superagers Using Resting-State fMRI

BACKGROUND AND PURPOSE: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields. MATERIALS AND METHODS: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks. RESULTS: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set. CONCLUSIONS: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers

Quality of life and burden in carers for persons with Chronic Obstructive Pulmonary Disease receiving oxygen therapy

OBJECTIVE:to assess the quality of life and burden of caregivers to Chronic Obstructive Pulmonary Disease patients on Long-Term Oxygen Therapy and to investigate the factors influencing this burden.METHOD:this is an analytical, cross-sectional study of 80 persons with Chronic Obstructive Pulmonary Disease on Long-Term Oxygen Therapy who used the specialized outpatient center of the Federal University of São Paulo, and their carers. The following instruments were used: Medical Outcomes Studies 36 (SF-36), Caregiver Burden Scale (CBS) and the Katz Index, along with socio-demographic and clinical variables.RESULTS:the most compromised scores on the carers' quality of life questionnaire were for Vitality and Mental Health. On the Caregiver Burden Scale, the domain which created the greatest burden for carers was the Environment. With the exception of Emotional Involvement, all the domains of quality of life were affected negatively by the domains of caregiver burden.CONCLUSION:it was shown that carers' quality of life was compromised and that they were overburdened with care tasks, confirming that assisting persons with Chronic Obstructive Pulmonary Disease is an important element in carers' quality of life.OBJETIVO:evaluar la calidad de vida y la sobrecarga de cuidados experimentada por cuidadores de portadores de la Enfermedad Pulmonar Obstructiva Crónica en uso de Oxigenoterapia Domiciliar Prolongada e investigar los factores que influencian esa sobrecarga.MÉTODO:se trata de estudio transversal analítico, con 80 portadores de la Enfermedad Pulmonar Obstructiva Crónica en uso de Oxigenoterapia Domiciliar en el ambulatorio especializado de la Universidad Federal de São Paulo y de sus respectivos cuidadores, aplicando los instrumentos: Medical Outcomes Studies 36 (SF-36), Caregiver Burden Scale (CBS), índice de Katz y variables sociodemográficas y clínicas.RESULTADOS:los puntajes del cuestionario de calidad de vida de los cuidadores más comprometidos fueron la Vitalidad y la Salud Mental. El Ambiente fue el dominio del Caregiver Burden Scale que generó mayor sobrecarga de cuidados. Con excepción del Envolvimiento Emocional, todos los dominios de calidad de vida fueron influenciados de forma negativa por los dominios de sobrecarga de cuidados.CONCLUSIÓN:se demostró que la calidad de vida y la sobrecarga de cuidados, de los cuidadores, estaban comprometidos, confirmando que cuidar a los portadores de Enfermedad Pulmonar Obstructiva Crónica, es un importante interviniente en la calidad de vida del cuidador.OBJETIVO:avaliar a qualidade de vida e a sobrecarga de cuidados, vivenciada por cuidadores de portadores de Doença Pulmonar Obstrutiva Crônica, em uso de Oxigenoterapia Domiciliar Prolongada, e investigar os fatores que influenciam essa sobrecarga.MÉTODO:trata-se de estudo transversal analítico, com 80 portadores de Doença Pulmonar Obstrutiva Crônica em uso de Oxigenoterapia Domiciliar do ambulatório especializado da Universidade Federal de São Paulo e seus respectivos cuidadores, aplicando-se os instrumentos: Medical Outcomes Studies 36, Caregiver Burden Scale, índice de Katz e variáveis sociodemográficas e clínicas.RESULTADOS:os escores do questionário de qualidade de vida dos cuidadores mais comprometidos foram vitalidade e saúde mental. O ambiente foi o domínio do Caregiver Burden Scale que gerou maior sobrecarga de cuidados. Com exceção do envolvimento emocional, todos os domínios de qualidade de vida foram influenciados de forma negativa pelos domínios de sobrecarga de cuidados.CONCLUSÃO:demonstrou-se comprometimento da qualidade de vida e sobrecarga de cuidados dos cuidadores, confirmando que assistir portadores de Doença Pulmonar Obstrutiva Crônica é um importante interveniente na qualidade de vida do cuidador.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de EnfermagemUniversidade Federal de São Paulo (UNIFESP) Hospital São PauloUNIFESP, Escola Paulista de Enfermagem (EPE)UNIFESP, Hospital São PauloSciEL

Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites

RecA plays a key role in homologous recombination, the induction of the DNA damage response through LexA cleavage and the activity of error-prone polymerase in Escherichia coli. RecA interacts with multiple partners to achieve this pleiotropic role, but the structural location and sequence determinants involved in these multiple interactions remain mostly unknown. Here, in a first application to prokaryotes, Evolutionary Trace (ET) analysis identifies clusters of evolutionarily important surface amino acids involved in RecA functions. Some of these clusters match the known ATP binding, DNA binding, and RecA-RecA homo-dimerization sites, but others are novel. Mutation analysis at these sites disrupted either recombination or LexA cleavage. This highlights distinct functional sites specific for recombination and DNA damage response induction. Finally, our analysis reveals a composite site for LexA binding and cleavage, which is formed only on the active RecA filament. These new sites can provide new drug targets to modulate one or more RecA functions, with the potential to address the problem of evolution of antibiotic resistance at its root

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Search for subsolar-mass black hole binaries in the second part of Advanced LIGO’s and Advanced Virgo’s third observing run

We describe a search for gravitational waves from compact binaries with at least one component with mass 0.2–1.0 M and mass ratio q ≥ 0.1 in Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Advanced Virgo data collected between 2019 November 1, 15:00 UTC and 2020 March 27, 17:00 UTC. No signals were detected. The most significant candidate has a false alarm rate of 0.2 yr−1. We estimate the sensitivity of our search over the entirety of Advanced LIGO’s and Advanced Virgo’s third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs fPBH 0.6 (at 90 per cent confidence) in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions, we are unable to rule out fPBH = 1. For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes, we find an upper bound fDBH < 10−5 on the fraction of atomic dark matter collapsed into black holes