Background Frailty has been conceptualized as a wasting disorder with weight loss as a key component. However, obesity is associated with disability and with physiological markers also recently ...linked with frailty, for example, increased inflammation and low antioxidant capacity. We aimed to explore the relationship between frailty and body mass index (BMI) in older people. Methods Data were from 3,055 community-dwelling adults aged 65 years and older who participated in the English Longitudinal Study of Ageing. Frailty was defined both by an index of accumulated deficits and by the Fried phenotype. BMI was divided into five categories, and waist circumference 88 cm or more (for women) and 102 cm or more (for men) was defined as high. Analyses were adjusted for sex, age, wealth, level of education, and smoking status. Results The association between BMI and frailty showed a U-shaped curve. This relationship was consistent across different frailty measures. The lowest frailty index (FI) scores and lowest prevalence of Fried frailty were in those with BMI 25–29.9. At each BMI category, and using either measure of frailty, those with a high waist circumference were significantly more frail. Conclusions Both the phenotypic definition of frailty and the FI show increased levels of frailty among those with low and very high BMIs. In view of the rise in obesity in older populations, the benefits and feasibility of diet and exercise for obese older adults should be a focus of urgent inquiries. The association of frailty with a high waist circumference, even among underweight older people, suggests that truncal obesity may be an additional target for intervention.
Background To date little conclusive evidence exists on the seasonality of rotavirus incidence in the tropics. We present a systematic review and meta-analysis on the seasonal epidemiology of ...rotavirus in the tropics, including 26 studies reporting continuous monthly rotavirus incidence for which corresponding climatological data was available. Methods Using linear regression models that account for serial correlation between months, monthly rotavirus incidence was significantly negatively correlated with temperature, rainfall and relative humidity in 65%, 55% and 60% of studies, respectively. We carried out pooled analyses using a generalized estimating equation (GEE) that accounts for correlation from between-study variation and serial correlation between months within a given study. Results For every 1°C (1.8°F) increase in mean temperature, 1 cm (0.39 in.) increase in mean monthly rainfall, and 1% increase in relative humidity (22%) this analysis showed reductions in rotavirus incidence of 10% (95% CI: 6–13%), 1% (95% CI: 0–1%), and 3% (95% CI:0–5%), respectively. Conclusions On the basis of the evidence, we conclude that rotavirus responds to changes in climate in the tropics, with the highest number of infections found at the colder and drier times of the year.
Circadian clocks provide a competitive advantage in an environment that is heavily influenced by the rotation of the Earth, by driving daily rhythms in behaviour, physiology and metabolism in ...bacteria, fungi, plants and animals. Circadian clocks comprise transcription-translation feedback loops, which are entrained by environmental signals such as light and temperature to adjust the phase of rhythms to match the local environment. The production of sugars by photosynthesis is a key metabolic output of the circadian clock in plants. Here we show that these rhythmic, endogenous sugar signals can entrain circadian rhythms in Arabidopsis thaliana by regulating the gene expression of circadian clock components early in the photoperiod, thus defining a 'metabolic dawn'. By inhibiting photosynthesis, we demonstrate that endogenous oscillations in sugar levels provide metabolic feedback to the circadian oscillator through the morning-expressed gene PSEUDO-RESPONSE REGULATOR 7 (PRR7), and we identify that prr7 mutants are insensitive to the effects of sucrose on the circadian period. Thus, photosynthesis has a marked effect on the entrainment and maintenance of robust circadian rhythms in A. thaliana, demonstrating that metabolism has a crucial role in regulation of the circadian clock.
Transport barrier formation and its relation to sheared flows in fluids and plasmas are of fundamental interest in various natural and laboratory observations and of critical importance in achieving ...an economical energy production in a magnetic fusion device. Here we report the first observation of an edge transport barrier formation event in an electrostatic gyrokinetic simulation carried out in a realistic diverted tokamak edge geometry under strong forcing by a high rate of heat deposition. The results show that turbulent Reynolds-stress-driven sheared E×B flows act in concert with neoclassical orbit loss to quench turbulent transport and form a transport barrier just inside the last closed magnetic flux surface.
Stem cells maintain tissues and organs over the lifespan of individuals. How aging influences this process is unclear. Here we investigate the effects of aging on C. elegans germline stem/progenitor ...cells and show that the progenitor pool is depleted over time in a manner dependent on inhibition of DAF-16/FOXO by insulin/IGF-1 signalling (IIS). Our data indicate that DAF-16/FOXO activity in certain somatic gonad cells is required for germline progenitor maintenance, and that this role is separable from the effect of DAF-16/FOXO on organismal aging. In addition, blocking germ cell flux, similar to reducing IIS, maintains germline progenitors. This effect is partially dependent on gonadal DAF-16/FOXO activity. Our results imply that (1) longevity pathways can regulate aging stem cells through anatomically separable mechanisms, (2) stem cell maintenance is not necessarily prioritized and (3) stem cell regulation can occur at the level of an entire organ system such as the reproductive system.
Solvent organization is a key but underexploited contributor to the thermodynamics of protein–ligand recognition, with implications for ligand discovery, drug resistance, and protein engineering. ...Here, we explore the contribution of solvent to ligand binding in the Haemophilus influenzae virulence protein SiaP. By introducing a single mutation without direct ligand contacts, we observed a >1000-fold change in sialic acid binding affinity. Crystallographic and calorimetric data of wild-type and mutant SiaP showed that this change results from an enthalpically unfavorable perturbation of the solvent network. This disruption is reflected by changes in the normalized atomic displacement parameters of crystallographic water molecules. In SiaP’s enclosed cavity, relative differences in water-network dynamics serve as a simple predictor of changes in the free energy of binding upon changing protein, ligand, or both. This suggests that solvent structure is an evolutionary constraint on protein sequence that contributes to ligand affinity and selectivity.
The proliferation/differentiation balance of stem and progenitor cell populations must respond to the physiological needs of the organism 1, 2. Mechanisms underlying this plasticity are not well ...understood. The C. elegans germline provides a tractable system to study the influence of the environment on progenitor cells (stem cells and their proliferative progeny). Germline progenitors accumulate during larval stages to form an adult pool from which gametes are produced. Notch pathway signaling from the distal tip cell (DTC) niche to the germline maintains the progenitor pool 3–5, and the larval germline cell cycle is boosted by insulin/IGF-like receptor signaling 6. Here we show that, independent of its role in the dauer decision, TGF-β regulates the balance of proliferation versus differentiation in the C. elegans germline in response to sensory cues that report population density and food abundance. Ciliated ASI sensory neurons are required for TGF-β-mediated expansion of the larval germline progenitor pool, and the TGF-β receptor pathway acts in the germline stem cell niche. TGF-β signaling thereby couples germline development to the quality of the environment, providing a novel cellular and molecular mechanism linking sensory experience of the environment to reproduction.
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► TGF-β influences the C. elegans germline proliferation versus differentiation balance ► TGF-β receptor signal transduction occurs in the DTC, the germline stem cell niche ► TGF-β is produced in ASI neurons and mediates pheromone and food cues ► TGF-β signaling links environmental cues to germ cell development
A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core ...electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. This Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and time scales of cold-pulse experiments in tokamak plasmas.
delirium and frailty are common among hospitalised older people but delirium is often missed and frailty considered difficult to measure in clinical practice.
to explore the relationship between ...delirium and frailty in older inpatients and determine their impact on survival.
the prospective cohort study of 273 patients aged ≥75 years.
patients were screened for delirium at presentation and on alternate days throughout their hospital stay. Frailty status was measured by an index of accumulated deficits (FI), giving a potential score from 0 (no deficits) to 1.0 (all 33 deficits), with 0.25 used as the cut-off between 'fit' and 'frail'.
delirium was detected in 102 patients (mean FI: 0.33) and excluded in 171 (mean FI: 0.18) (P < 0.005); 111 patients were frail. Among patients with delirium, the median survival in fit patients was 359 days (95% CI: 118-600) compared with 88 days for those who were frail (95% CI: 5-171; P < 0.05).
delirium was associated with higher levels of frailty: the identification of frail patients may help to target those at a greatest risk of delirium. Survival following delirium was poor with the combination of frailty and delirium conferring a particularly bleak prognosis.
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