Interactive effects of intrinsic capacity and obesity on the KDIGO chronic kidney disease risk classification in older patients with type 2 diabetes mellitus.

BACKGROUND: Intrinsic capacity (IC) is a novel concept focusing on normal and healthy aging. The effect of IC on the risk of chronic kidney disease (CKD) according to KDIGO category in older type 2 diabetes mellitus (T2DM) patients has rarely been studied. We investigated whether a decline in IC is associated with the risk of CKD according to KDIGO 2012 categories. METHODS: This is a cross-sectional study. The exposure variables (IC score and body mass index) and outcome variable (KDIGO categories of the risk of CKD) were collected at the same timepoint. A total of 2482 older subjects with T2DM managed through a disease care program were enrolled. The five domains of IC, namely locomotion, cognition, vitality, sensory, and psychological capacity were assessed. Based on these domains, the IC composite score was calculated. CKD risk was classified according to the KDIGO 2012 CKD definition. Univariate and multivariate analyses were used to assess the association between IC score and KDIGO categories of risk of CKD. RESULTS: The KDIGO CKD risk category increased in parallel with IC score (p for trend < 0.0001). In multivariate analysis, compared to those with an IC score 0, the odds ratio of having a KDIGO moderately increased to very high risk category of CKD was 1.76 (1.31-2.37) times higher for those with an IC score of 2-5. Furthermore, an increased IC score was associated with a higher prevalence of moderate and severe obesity. Moreover, there was a synergistic interaction between IC score and obesity on the KDIGO moderately increased to very high risk category of CKD (synergy index = 1.683; 95% CI 0.630-3.628), and the proportion of the KDIGO moderately increased to very high risk category of CKD caused by this interaction was 25.6% (attributable proportion of interaction = 0.256). CONCLUSIONS: Our findings indicate that IC score may be closely related to the KDIGO moderately increased to very high risk category of CKD. In addition, there may be a synergistic interaction between IC score and obesity, and this synergistic interaction may increase the KDIGO CKD risk stage.

Enterovirus A71 Induces Neurological Diseases and Dynamic Variants in Oral Infection of Human SCARB2-Transgenic Weaned Mice.

Enterovirus A71 (EV-A71) and many members of the Picornaviridae family are neurotropic pathogens of global concern. These viruses are primarily transmitted through the fecal-oral route, and thus suitable animal models of oral infection are needed to investigate viral pathogenesis. An animal model of oral infection was developed using transgenic mice expressing human SCARB2 (hSCARB2 Tg), murine-adapted EV-A71/MP4 virus, and EV-A71/MP4 virus with an engineered nanoluciferase gene that allows imaging of viral replication and spread in infected mice. Next-generation sequencing of EV-A71 genomes in the tissues and organs of infected mice was also performed. Oral inoculation of EV-A71/MP4 or nanoluciferase-carrying MP4 virus stably induced neurological symptoms and death in infected 21-day-old weaned mice. In vivo bioluminescence imaging of infected mice and tissue immunostaining of viral antigens indicated that orally inoculated virus can spread to the central nervous system (CNS) and other tissues. Next-generating sequencing further identified diverse mutations in viral genomes that can potentially contribute to viral pathogenesis. This study presents an EV-A71 oral infection murine model that efficiently infects weaned mice and allows tracking of viral spread, features that can facilitate research into viral pathogenesis and neuroinvasion via the natural route of infection. IMPORTANCE Enterovirus A71 (EV-A71), a positive-strand RNA virus of the Picornaviridae, poses a persistent global public health problem. EV-A71 is primarily transmitted through the fecal-oral route, and thus suitable animal models of oral infection are needed to investigate viral pathogenesis. We present an animal model of EV-A71 infection that enables the natural route of oral infection in weaned and nonimmunocompromised 21-day-old hSCARB2 transgenic mice. Our results demonstrate that severe disease and death could be stably induced, and viral invasion of the CNS could be replicated in this model, similar to severe real-world EV-A71 infections. We also developed a nanoluciferase-containing EV-A71 virus that can be used with this animal model to track viral spread after oral infection in real time. Such a model offers several advantages over existing animal models and can facilitate future research into viral spread, tissue tropism, and viral pathogenesis, all pressing issues that remain unaddressed for EV-A71 infections.

Factors affecting trajectory patterns of self-rated health (SRH) in an older population--a community-based longitudinal study.

Self-rated health (SRH) is considered a relevant and important predictor for major health outcomes in the older population. SRH status may interact with certain factors and change over a person's lifetime. In this study, we sought to characterize profiles of older people over time by constructing prototypical trajectories of the variable of interest, namely SRH. The underlying assumption was that the collection of observed individual trajectories could be efficiently summarized by a smaller set of latent clusters of those trajectories. Data was obtained from the Longitudinal Survey of Health and Living Status of the Elderly in Taiwan, which was conducted between 1989 and 2003 and included five separate waves of survey. A total of 3937 subjects aged 60 or older (2251 males and 1686 females) comprised the major analytic cohort. Latent Class Growth Analysis (LCGA) was used to identify developmental classes of trajectory patterns in SRH. The results showed that during a 14-year period, SRH developed five major longitudinal trajectories. Less than one-third of the older population was able to maintain their formerly good or moderate health status; when change occurred, decline was more likely than improvement. In addition, LCGA indicated that many demographic characteristics, as well as physical and psychological propensities, were associated with poor SRH in the older population. Specifically, these factors played a role in involving baseline SRH level and its trend toward deterioration in later life. Health care professionals must understand the various longitudinal patterns and factors affecting SRH trajectories if they are to develop programs aimed at maintaining the older population's health and well-being.

Trajectory stability and factors affecting trajectories over time of the longitudinal age-related change in physical performance among older people.

This study used community-based cohort data to explore the trajectory stability (tracking coefficient or stability coefficient) and its influencing factors on the longitudinal age-related change in physical performance among older populations. An integrated statistical method with generalized estimating equations was applied to study trajectory stability. The study particularly demonstrated a mixed representation regarding the significant trajectories of intact and reduced physical performance over time. It is important to note that the trajectory stability of reduced physical performance was higher in females (odds ratio [OR] = 7.76; 95% confidence interval [CI]: 5.04-11.93) than in males (OR = 5.65; 95% CI: 4.09-7.79). However, for intact physical performance, the coefficient was 3.52 (95% CI: 2.76-4.48) in males and 2.55 (95% CI: 1.91-3.41) in females. There are further gender differences based on the influence of demographic, psychological, lifestyle, and biological variables in relation to the trajectories of physical performance. The authors conclude that an understanding of trajectory stability, as well as the factors affecting these trajectories in physical performance, is essential to the development of prevention programs tailored to maintaining functional ability or preventing the loss of physical function among older people.

Time-varying nature of risk factors for the longitudinal development of disability in older adults with arthritis.

BACKGROUND: To investigate changes over time in risk factors for the development of Activities of Daily Living (ADL) disabilities in older adults with arthritis. METHODS: The data were obtained from the Longitudinal Survey of Health and Living Status of the Elderly in Taiwan (1989-1999). The major analytic cohort comprised 977 older adults (458 men and 519 women) with arthritis and without ADL limitation at study baseline. A generalized estimating equations (GEE) model was used to analyze all temporally correlated errors, population-averaged estimates, and longitudinal relationships. RESULTS: Overall, the cumulative incidence of ADL disability in the analytic cohort was 17.4% during an observation period of 11 years. With respect to baseline risk, ADL disability was associated with older age, presence of comorbid chronic conditions, and poor self-rated health. However, the findings changed after accounting for the time-varying nature of risk factors and the temporal sequence of possible cause-and-effect relationships. In addition to the baseline predictors, a high score on the Center for Epidemiologic Studies Depression Scale, lack of regular exercise, and becoming widowed were associated with an increased risk of ADL disability and a decreased chance of recovery. CONCLUSIONS: An understanding of the time-varying nature of risk factors for the disabling process is essential for the development of effective interventions that aim to maintain functional ability and prevent limitations among older adults with arthritis.