Dietary Supplement Use in Middle-aged and Older Adults.

OBJECTIVES: Despite limited evidence of clinical benefits, dietary supplement use is increasingly common among older adults. The aim of this study was to characterise the prevalence of dietary supplement use in a national sample of community-dwelling middle-aged and older adults and investigate factors associated with its use. DESIGN/SETTING/PARTICIPANTS: This was a cross-sectional study using data from the Health and Retirement Study (HRS), a biennial, nationally representative survey of individuals aged 50 years and older in the United States. This study combined data from the 2013/14 Health Care and Nutrition Survey (HCNS) and 2012 Core Survey. MEASUREMENTS: The primary outcome was the use of any dietary supplement at least once a week. Secondary outcomes were the use of multivitamins and specific vitamin and supplement types. Multivariable regression models were used to identify factors associated with any dietary supplement use. RESULTS: A total of 6045 participants (weighted n = 71,268,015) were included in the final analytical sample (mean age 67.7 years, 59.3% female). Of these, 84.6% (n=60,292,704) were regular dietary supplement users, with participants taking a mean of 3.2±0.1 different dietary supplements and 41.9% taking four or more. Multivitamins were the most common, used by 57.5% (n=41,147,146) of participants. Other commonly used dietary supplements were vitamin D, fish oil, calcium, vitamin C, and vitamin B12. Older age (75+ years), female sex, higher education, daily alcohol use, vigorous physical activity, regular medication use, and arthritis were associated with higher odds of dietary supplement use. CONCLUSIONS: In this sample of middle-aged and older Americans, more than 4 out of 5 used a dietary supplement. Certain demographic, behavioural, and clinical factors were associated with their use. Given the lack of evidence for improving health outcomes, our findings suggest potential overuse of dietary supplements in people over the age of 50.

Eclipse-induced wind changes over the British Isles on the 20 March 2015.

The British Isles benefits from dense meteorological observation networks, enabling insights into the still-unresolved effects of solar eclipse events on the near-surface wind field. The near-surface effects of the solar eclipse of 20 March 2015 are derived through comparison of output from the Met Office's operational weather forecast model (which is ignorant of the eclipse) with data from two meteorological networks: the Met Office's land surface station (MIDAS) network and a roadside measurement network operated by Vaisala. Synoptic-evolution relative calculations reveal the cooling and increase in relative humidity almost universally attributed to eclipse events. In addition, a slackening of wind speeds by up to about 2 knots in already weak winds and backing in wind direction of about 20° under clear skies across middle England are attributed to the eclipse event. The slackening of wind speed is consistent with the previously reported boundary layer stabilization during eclipse events. Wind direction changes have previously been attributed to a large-scale 'eclipse-induced cold-cored cyclone', mountain slope flows, and changes in the strength of sea breezes. A new explanation is proposed here by analogy with nocturnal wind changes at sunset and shown to predict direction changes consistent with those observed.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'.

Atmospheric changes from solar eclipses.

This article reviews atmospheric changes associated with 44 solar eclipses, beginning with the first quantitative results available, from 1834 (earlier qualitative accounts also exist). Eclipse meteorology attracted relatively few publications until the total solar eclipse of 16 February 1980, with the 11 August 1999 eclipse producing the most papers. Eclipses passing over populated areas such as Europe, China and India now regularly attract scientific attention, whereas atmospheric measurements of eclipses at remote locations remain rare. Many measurements and models have been used to exploit the uniquely predictable solar forcing provided by an eclipse. In this paper, we compile the available publications and review a subset of them chosen on the basis of importance and novelty. Beyond the obvious reduction in incoming solar radiation, atmospheric cooling from eclipses can induce dynamical changes. Observations and meteorological modelling provide evidence for the generation of a local eclipse circulation that may be the origin of the 'eclipse wind'. Gravity waves set up by the eclipse can, in principle, be detected as atmospheric pressure fluctuations, though theoretical predictions are limited, and many of the data are inconclusive. Eclipse events providing important early insights into the ionization of the upper atmosphere are also briefly reviewed.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'.

The National Eclipse Weather Experiment: an assessment of citizen scientist weather observations.

The National Eclipse Weather Experiment (NEWEx) was a citizen science project designed to assess the effects of the 20 March 2015 partial solar eclipse on the weather over the United Kingdom (UK). NEWEx had two principal objectives: to provide a spatial network of meteorological observations across the UK to aid the investigation of eclipse-induced weather changes, and to develop a nationwide public engagement activity-based participation of citizen scientists. In total, NEWEx collected 15 606 observations of air temperature, cloudiness and wind speed and direction from 309 locations across the UK, over a 3 h window spanning the eclipse period. The headline results were processed in near real time, immediately published online, and featured in UK national press articles on the day of the eclipse. Here, we describe the technical development of NEWEx and how the observations provided by the citizen scientists were analysed. By comparing the results of the NEWEx analyses with results from other investigations of the same eclipse using different observational networks, including measurements from the University of Reading's Atmospheric Observatory, we demonstrate that NEWEx provided a fair representation of the change in the UK meteorological conditions throughout the eclipse. Despite the simplicity of the approach adopted, robust reductions in both temperature and wind speed during the eclipse were observed.This article is part of the themed issue 'Atmospheric effects of solar eclipses stimulated by the 2015 UK eclipse'.

Second messengers, steroids and signaling cascades: Crosstalk in sperm development and function.

Signaling cascades control numerous aspects of sperm physiology, ranging from creation to fertilization. Novel aspects of several kinases and their influence on sperm development will be discussed in the first section and cover proliferation, chromatin remodeling and morphology. In the second section, protein kinases (A, B and C) that affect sperm function and their regulation by second messengers, cyclic-AMP and phosphoinositides, as well as steroids will be featured. Key areas of integration will be presented on the topics of sperm motility, capacitation, acrosome reaction and fertilization.

The predictive value of structured ultrasonographic staging for thyroid nodules.

BACKGROUND: 'R staging' is a new ultrasonographic scoring system developed and used by our specialist head and neck radiologist for reporting sonographic risk of malignancy to those at our thyroid multidisciplinary team meeting. This study aimed to: classify the R staging system, examine its relationship with the eventual histopathological diagnosis and define its clinical utility. METHODS: The pre-operative ultrasound scans of 78 patients were assigned an R status by our specialist head and neck radiologist. The final histopathology report for each thyroid nodule was used as the 'gold standard' for analysis. RESULTS: When thyroid nodules were classified as low risk (R stages 1-3) or high risk (R stages 4-5) for malignancy, the sensitivity of R staging was 74.2 per cent and specificity was 80.9 per cent. An R5 status was 100 per cent predictive of malignancy. CONCLUSION: Our results compare favourably with other suggested ultrasonographic staging systems for thyroid nodules.

Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques.

OBJECTIVES: Observational and experimental studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD); however, clinical trials and other observational studies, including the Adult Changes in Thought (ACT) study, show no protection or promotion of AD. The objective of this study is to determine the relationship between common dementia-associated pathologies and mid- to late-life NSAID exposure. METHODS: We examined the association of mid- to late-life NSAID use with neuropathologic findings on 257 autopsies from ACT, a population-based study of brain aging and incident dementia. Cumulative standard daily doses (SDD) of nonselective NSAIDs were determined from ≥10 years of computerized pharmacy dispensing data. Analyses were adjusted for selection bias to broaden generalizability of results to 3,026 eligible participants in the ACT cohort. Seven pathologic indices were evaluated: intermediate or frequent score for neuritic plaques, Braak stages V or VI for neurofibrillary tangles, >2 cerebral microinfarcts, the presence of any neocortical Lewy bodies, any macroscopic infarcts, any amyloid angiopathy, and moderate or severe atherosclerosis. RESULTS: Of the neuropathologic indices evaluated, only neuritic plaque score was significantly increased in participants with greater use of nonselective NSAIDs (p = 0.065), specifically in those with high levels of cumulative use: 1,000-2,000 SDD (adjusted relative risk [RR] 2.16, 95% confidence interval [CI] 1.02-4.25, compared to light/nonuse [<60 SDD]) and >2,000 SDD (adjusted RR 2.37, 95% CI 1.24-4.67). CONCLUSIONS: Increased neuritic plaque accumulation may explain the association between heavy use of nonselective NSAIDs and increased risk of dementia among ACT participants.

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer dementia (AD). METHODS: We analyzed the association of prior NSAID exposure with incident dementia and AD in the Adult Changes in Thought population-based cohort aged > or = 65 years (median 74.8) at enrollment. Participants were members of Group Health, which provided computerized pharmacy dispensing records from 1977 onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy data, following them biennially for up to 12 years to identify dementia and AD. Cox proportional hazards regression assessed association of dementia or AD with NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g., heavy use = 500 + SDD), with some analyses also adding consecutive biennial self-reports of NSAID use. RESULTS: Pharmacy records identified 351 participants (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy users during follow-up. Some 476 individuals developed incident dementia, 356 with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence interval, 1.24-2.24) and 1.57 (95% confidence interval, 1.10-2.23). Addition of self-reported exposure data did not alter these results. CONCLUSIONS: These findings differ from those of other studies with younger cohorts. The results observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could result in increased AD incidence in late old age. The relation of NSAID use and AD pathogenesis needs further investigation.

Mouse models of PPAR-gamma deficiency: dissecting PPAR-gamma's role in metabolic homoeostasis.

The identification of humans with mutations in PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) has underlined its importance in the pathogenesis of the metabolic syndrome. Genetically modified mice provide powerful tools to dissect the mechanisms by which PPAR-gamma regulates metabolic processes. Ablation of PPAR-gamma in vivo is lethal and thus dissection of PPAR-gamma function using mouse models has relied on the development of tissue and isoform-specific ablation and mouse models of human mutations. These models exhibit phenotypes of partial PPAR-gamma impairment and are useful to elucidate how PPAR-gamma regulates specific metabolic processes. These murine models have confirmed the involvement of PPAR-gamma in adipose tissue development, maintenance and distribution. The mechanism involved in PPAR-gamma regulation of glucose homoeostasis is obscure as both agonism and partial impairment of PPAR-gamma increase insulin sensitivity. While adipose tissue is likely to be the primary target for the insulin-sensitizing effects of PPAR-gamma, some murine models suggest PPAR-gamma expressed outside adipose tissue may also contribute actively to maintain glucose homoeostasis. Interestingly, mutations in PPAR-gamma that cause severe insulin resistance in humans when expressed in mice do not result in insulin insensitivity. However, these murine models can recapitulate the effects in fuel partitioning, post-prandial lipid handling and vasculature dysfunction observed in humans. In summary, these murine models of PPAR-gamma have provided useful in vivo systems to dissect the function of PPAR-gamma, but additionally have revealed a picture of complexity. These models have confirmed a key role for PPAR-gamma in the metabolic syndrome; however, they challenge the concept that insulin resistance is the main factor linking the clinical manifestations of the metabolic syndrome.

Factors affecting choice of community residential care setting.

UNLABELLED: To investigate factors associated with residents' choice of type of Medicaid-funded community residential care setting in western Washington State. METHOD: Prospective cohort design including residents new to any of three setting types (264 residents entering 170 different facilities), using data from state and Medicaid databases and in-person interviews. The authors used analysis of variance and multinomial logistic regression to examine bivariate associations and estimate effects of resident and facility characteristics on choice of facility type at baseline. RESULTS: Several resident characteristics appear to be associated with choice of community residential care setting, including age, marital status, education, functional status, and reported memory and behavior problems. Facility policies differ significantly among types of facilities and also appear to be associated with choice of setting. DISCUSSION: Selection processes operate in choice of community residential care setting, with residents choosing facility type based on the fit of their needs with facility characteristics.

Measurement of leptin and insulin-like growth factor-I in seminal plasma from different species.

The multi-functional proteins, insulin-like growth factor-I (IGF-I) and leptin were present in seminal plasma from different species. Concentrations of IGF-I in equine and porcine semen were 20 and 17.5 ng/ml, respectively. Seminal plasma concentrations of leptin were 1 ng/ml in human and 11 ng/ml in porcine samples.

Targeted disruption of the pituitary adenylate cyclase-activating polypeptide gene results in early postnatal death associated with dysfunction of lipid and carbohydrate metabolism.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hormone belonging to the glucagon superfamily of hormones. These hormones are known to play important roles in metabolism and growth. PACAP is a neuropeptide that causes accumulation of cAMP in a number of tissues and affects the secretion of other hormones, vasodilation, neural and immune functions, as well as the cell cycle. To determine whether PACAP is essential for survival and to evaluate its function(s), we have generated mice lacking the PACAP gene via homologous recombination. We found that most PACAP null mice died in the second postnatal week in a wasted state with microvesicular fat accumulation in liver, skeletal muscle, and heart. Gas chromatography-mass spectrometry showed that fatty acid beta-oxidation in liver mitochondria of PACAP(-/-) mice was not blocked based on the distribution of 3-hydroxy-fatty acids (C6-16) in the plasma. Instead, increased metabolic flux through the beta-oxidation pathway was suggested by the presence of ketosis. Also, serum triglycerides and cholesterol were significantly higher (2- to 3-fold) in PACAP null mice than littermates. In the fed state, both serum insulin and blood glucose were normal in 5-d-old null mice compared with their littermates. In contrast, fasted PACAP null pups had a significant increase in insulin, but a decrease in blood glucose compared with littermates. Glycogen in the liver was reduced. These results suggest PACAP is a critical hormonal regulator of lipid and carbohydrate metabolism.

Residues from anabolic preparations after good veterinary practice.

The purpose of this study was to determine the endogenous concentrations of estrogens, particularly estradiol-17beta (E2beta, in edible tissues of beef cattle (females and intact and neutered males) and the concentrations of E2beta, and trenbolone beta and alpha (betaTb, alphaTb) after an E2beta and/or trenbolone acetate (TA) ear implant. Radioimmunoassays were validated for quantitation of E2beta (active isomer), E2alpha, estrone (E1), betaTb and alphaTb for bovine muscle, liver, kidney and fat tissues. The criteria of accuracy, precision, specificity and sensitivity were applied according to the standards of the U.S. Food & Drug Administration. In steer tissues, endogenous E2beta was <15 ppt, as was heifer muscle; but heifer liver and kidney were 3-fold greater. An E2beta implant in steers had no effect on muscle E2beta concentration, but increased E2beta in liver and fat 4- and 3-fold, respectively, but by 24 h post-implant removal, E2beta had fallen by half. Tissue E1 concentrations in cyclic females were similar to E2beta, but rose many fold greater than did E2beta during gestation; E2beta rose 3-fold during gestation. After E2beta/TA implant, steer tissues had E2beta concentrations equal to (for muscle and fat) and one-half (for liver) the E2beta measured in E2beta implant only steers; betaTb was in a low range (250-380 ppt) in muscle, liver and fat and alphaTb was even lower, except in liver (800-1500 ppt). An implant of TA only (no E2beta) resulted in betaTb and alphaTb concentrations 2-3-fold greater in liver, kidney and fat, but no greater in muscle than betaTb in tissues of E2beta/TA implant steers. In conclusion, anabolic implants in steers resulted in tissue E2beta concentrations less than the FDA allowable increment and betaTb in the lowest quartile (0.25) of a part per billion 30 days after implant.

Crosstalk and considerations in endocrine disruptor research.

The presence of endocrine disrupting chemicals in the environment has prompted action on several fronts to assess the potential health risks of these compounds. To fully understand the mechanisms behind the observed endocrine disruption, crosstalk and other factors should be considered. In this article we will discuss how crosstalk modulates estrogen action in several common assays and how this and other considerations appear to have been overlooked. In addition, a paradigm shift from theoretical linear response pathways to interaction maps should aid in the understanding and analysis of endocrine disruption.

Medication adherence in elderly patients receiving home health services following hospital discharge.

OBJECTIVE: To assess prevalence and risk factors for medication under- and overadherence in a two-week period following hospital discharge in adults > or = 65 years. DESIGN: Prospective, cohort study. SETTING: Three home healthcare agencies in Madison, Wisconsin, and surrounding vicinity. PARTICIPANTS: One hundred forty-seven older participants taking three or more medications who were hospitalized for medical illness, received home nursing after discharge, and completed the two-week interview. MEASUREMENTS: The main outcome measures were having at least one medication with less than 70% adherence (underadherence) and having at least one medication with more than 120% adherence (overadherence) based on pill counts. RESULTS: Forty-five (30.6%) participants were underadherent and 27 (18.4%) participants were overadherent with at least one medication> In a multivariate model, underadherence was predicted by poor cognition (OR 2.5; 95% CI 1.02 to 6.10) and higher medication use (OR 1.16; 95% CI 1.03 to 1.31, for each 1-unit increase in number of medications). Both poor cognition and low education were significantly associated with overadherence in univariate analysis; however, neither variable was significant once included in the multivariate model. CONCLUSIONS: Under- and overadherence to medications is common after hospital discharge. Poor cognition and a greater number of medications were associated with underadherence. Poor and lower education were markers for overadherence; however, further study is needed to determined whether these are independent predictors. Patients who have impaired cognition or are taking a greater number of medications after hospitalization may benefit from targeted interventions to monitor and improve medication compliance.

Synergistic approach to cancer therapy: exploiting interactions between anti-estrogens, retinoids, monoterpenes and tyrosine kinase inhibitors.

Non-responsiveness and toxicity are large problems encountered during cancer treatment. Utilization of compounds that synergize should increase treatment efficacy while avoiding problems of toxicity. This review explores interactions between classes of compounds, including anti-estrogens, retinoids, monoterpenes and tyrosine kinase inhibitors, that are effective independent, and how their synergistic interaction could be exploited in cancer treatment. The effects of these compounds on insulin-like growth factors (IGF) and transforming-growth factor-beta (TGF-beta) will also be examined.

Physiological basis for use of insulin-like growth factors in reproductive applications: a review.

The insulin-like growth factors (IGF-I and -II) are ubiquitously expressed factors that regulate cell growth, differentiation and maintenance of differentiated cell function. All aspects of male and female reproduction are influenced by the IGF system. This review will examine the IGF system as it pertains to reproductive physiology and applications.

Does the insulin-like growth factor system interact with prostaglandins and proinflammatory cytokines during neurodegeneration?

Prostaglandins and proinflammatory cytokines are implicated in the etiology of neurodegenerative diseases, such as Alzheimer's disease. Signaling cascades initiated by these factors may result in reactive oxygen species generation and cell death. The insulin-like growth factors (IGF) are ubiquitous polypeptides involved in all aspects of growth and development. Additionally, the IGF are regarded as survival factors that display potent antiapoptotic activity. Interfering with IGF production, distribution, or signaling may result in greater susceptibility to apoptotic stimuli. In neurodegenerative conditions, the IGF appear to be antagonized by prostaglandins and proinflammatory cytokines. In this review, the relationship among specific prostaglandins, the proinflammatory factors, tumor necrosis factor, interleukin-1, and interleukin-6, and the IGF system will be investigated.

Actions and interactions of the IGF system in Alzheimer's disease: review and hypotheses.

Insulin-like growth factors (IGF) are pleiotrophic polypeptides affecting all aspects of growth and development. The IGF system, including ligands, receptors, binding proteins and proteases is also involved in pathophysiological conditions, such as cancer and degenerative conditions. In this review, the actions and interactions of the IGF system as it relates to Alzheimer's disease will be investigated.