Serum 25-hydroxyvitamin D level and kidney function decline in a Swiss general adult population.

Molecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria. Baseline (2003-2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m(2)), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography-tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors. Among the 4280 people included in the analysis, the mean±SD annual eGFR change was -0.57±1.78 ml/min per 1.73 m(2), and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was -0.005 ml/min per 1.73 m(2) (95% confidence interval, -0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria. The association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.

Daily physical activities and sports in adult survivors of childhood cancer and healthy controls: a population-based questionnaire survey.

BACKGROUND: Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. METHODOLOGY/PRINCIPAL FINDINGS: The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976-2003 at age 0-15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5 years and reached adulthood (≥20 years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35 years: 1.5, 95CI 1.2-2.0), female gender (OR 1.6, 95CI 1.3-1.9), French/Italian Speaking (OR 1.4, 95CI 1.1-1.7), and higher education (OR for university education: 2.0, 95CI 1.5-2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1-1.6), older age (OR for ≥35 years: 1.4, 95CI 1.1-1.8), migration background (OR 1.5, 95CI 1.3-1.8), French/Italian speaking (OR 1.4, 95CI 1.2-1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2-2.2), being married (OR 1.7, 95CI 1.5-2.0), having children (OR 1.3, 95CI 1.4-1.9), obesity (OR 2.4, 95CI 1.7-3.3), and smoking (OR 1.7, 95CI 1.5-2.1). Type of diagnosis was only associated with sports. CONCLUSIONS/SIGNIFICANCE: Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population.

Cortical origin of functional recovery in the somatosensory cortex of the adult mouse after thalamic lesion

Résumé L'accident vasculaire cérébral sensoriel pur est un des syndromes lacunaires, dû à l'occlusion de petits vaisseaux cérébraux, souvent dans le cadre d'une lésion intéressant le noyau ventro-caudal du thalamus. Il produit un hémisyndrome sensitif pur, et parfois un syndrome douloureux se développe à distance de l'événement aigu. Afin d'étudier la récupération fonctionnelle dans le cortex somatosensoriel (SI) après une telle lésion dans le thalamus, un modèle de lésion excitotoxique a été développé dans le système somatosensoriel de la souris adulte, caractérisé par la présence de formations cytoarchitectoniques dans SI appelées "tonneaux". Chacun de ces tonneaux correspond à la représentation corticale d'une vibrisse du museau. L'activité métabolique a été mesurée dans SI à différents intervalles après la lésion, à l'aide de déoxyglucose marqué radioactivement. Dans les deux premiers jours suivant celle-ci, l'activité métabolique diminue de manière importante dans toutes les couches corticales, avec une atteinte plus marquée dans la couche IV, principale projection des axones thalamo-corticaux. Une récupération de l'activité métabolique se produit ensuite, d'autant plus marquée que le délai après la lésion est grand. Cette récupération s'observe dans toutes les couches coticales, les couches I et Vb récupérant plus rapidement que les couches II, III, IV, Va et VI. Cinq semaines après la lésion, l'absence des vibrisses correspondant à la partie déafférentée de SI diminue l'activité métabolique corticale de 32% et démontre l'activation par la périphérie de cette partie de l'écorce, malgré la perte des axones thalamo-corticaux provenant du noyau ventro-caudal. Des expériences de traçage rétrograde ont montré une augmentation des projections intracorticales sur la partie déafférentée de l'écorce, en particulier de longue distance, ainsi que des projections interhémisphériques, mais n'ont pas permis de mettre en évidence de nouvelle projection thalamique, indiquant une origine corticale à la récupération fonctionnelle observée. Abstract To study the degree and time course of the functional recovery in the somatosensory cortex (SI) after an excitotoxic lesion in the adult mouse thalamus, metabolic activity was determined in SI at various times points post lesion. Immediately after the lesion, metabolic activity in the thalamically deafferented part of SI was at its lowest value but increased progressively at subsequent time points. This was seen in all cortical layers, however, layers I and Vb recover more rapidly than layers II, III, IV, Va and VI. Removal of the mystacial whiskers corresponding to the deafferented area, 5 weeks after cortical recovery, produced a subsequent 32% drop in metabolic activity, demonstrating peripheral sensory activation of this part of the cortex. Tracing experiments revealed that the deafferented cortex did not receive a novel thalamic input, but cortico-cortical and contralateral barrel cortex projections to this area were reinforced. We conclude that the cortical functional recovery after a thalamic lesion is, at least partially, due to modified cortico-cortical and callosal projections to the deafferented cortical area.

Changes of overweight and obesity in the adult Swiss population according to educational level, from 1992 to 2007.

In many high income developed countries, obesity is inversely associated with educational level. In some countries, a widening gap of obesity between educational groups has been reported. The aim of this study was to assess trends in body mass index (BMI) and in prevalence of overweight and obesity and their association with educational level in the adult Swiss population. Four cross-sectional National health interview surveys conducted in 1992/93 (n = 14,521), 1997 (n = 12,474), 2002 (n = 18,908) and 2007 (n = 17,879) using representative samples of the Swiss population (age range 18-102 years). BMI was derived from self-reported data. Overweight was defined as BMI > or = 25 and <30 kg/m(2), and obesity as BMI > or = 30 kg/m(2). Mean (+/- standard deviation) BMI increased from 24.7 +/- 3.6 in 1992/3 to 25.4 +/- 3.6 kg/m2 in 2007 in men and 22.8 +/- 3.8 to 23.7 +/- 4.3 kg/m(2) in women. Between 1992/3 and 2007, the prevalence of overweight + obesity increased from 40.4% to 49.5% in men and from 22.3% to 31.3% in women, while the prevalence of obesity increased from 6.3% to 9.4% in men and from 4.9% to 8.5% in women. The rate of increase in the prevalence of obesity was greater between 1992/3 and 2002 (men: +0.26%/year; women: +0.31%/year) than between 2002 and 2007 (men: +0.10%/year; women: +0.10%/year). A sizable fraction (approximately 25%) of the increasing mean BMI was due to increasing age of the participants over time. The increase was larger in low than high education strata of the population. BMI was strongly associated with low educational level among women and this gradient remained fairly constant over time. A weaker similar gradient by educational level was apparent in men, but it tended to increase over time. In Switzerland, overweight and obesity increased between 1992 and 2007 and was associated with low education status in both men and women. A trend towards a stabilization of mean BMI levels was noted in most age categories since 2002. The increase in the prevalence of obesity was larger in low education strata of the population. These findings suggest that obesity preventive measures should be targeted according to educational level in Switzerland.

Intraseasonal variation in immune defence, body mass and hematocrit in adult house martins Delichon urbica

The intensity of parasite infections often increases during the reproductive season of the host as a result of parasite reproduction, increased parasite transmission and increased host susceptibility. We report within-individual variation in immune parameters, hematocrit and body mass in adult house martins Delichon urbica rearing nestlings in nests experimentally infested with house martin bugs Oeciacus hirundinis and birds rearing nestlings in initially parasite-free nests. From first to second broods body mass and hematocrit of breeding adult house martins decreased. In contrast leucocytes and immunoglobulins became more abundant. When their nests were infested with ectoparasites adults lost more weight compared with birds raising nestlings in nests treated with pyrethrin, whereas the decrease in hematocrit was more pronounced during infection with blood parasites. Neither experimental infestation with house martin bugs nor blood parasites had a significant effect on the amount of immune defences.

Immunogold Detection of L-glutamate and D-serine in Small Synaptic-Like Microvesicles in Adult Hippocampal Astrocytes.

Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (∼45 and ∼55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca(2+) increase can trigger release of glutamate and/or D-serine.

The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.

BACKGROUND: Hypotension, a common intra-operative incident, bears an important potential for morbidity. It is most often manageable and sometimes preventable, which renders its study important. Therefore, we aimed at examining hospital variations in the occurrence of intra-operative hypotension and its predictors. As secondary endpoints, we determined to what extent hypotension relates to the risk of post-operative incidents and death. METHODS: We used the Anaesthesia Databank Switzerland, built on routinely and prospectively collected data on all anaesthesias in 21 hospitals. The three outcomes were assessed using multi-level logistic regression models. RESULTS: Among 147,573 anaesthesias, hypotension ranged from 0.6% to 5.2% in participating hospitals, and from 0.3% up to 12% in different surgical specialties. Most (73.4%) were minor single events. Age, ASA status, combined general and regional anaesthesia techniques, duration of surgery and hospitalization were significantly associated with hypotension. Although significantly associated, the emergency status of the surgery had a weaker effect. Hospitals' odds ratios for hypotension varied between 0.12 and 2.50 (P < or = 0.001), even after adjusting for patient and anaesthesia factors, and for type of surgery. At least one post-operative incident occurred in 9.7% of the procedures, including 0.03% deaths. Intra-operative hypotension was associated with a higher risk of post-operative incidents and death. CONCLUSION: Wide variations remain in the occurrence of hypotension among hospitals after adjustment for risk factors. Although differential reporting from hospitals may exist, variations in anaesthesia techniques and blood pressure maintenance may also have contributed. Intra-operative hypotension is associated with morbidities and sometimes death, and constant vigilance must thus be advocated.

Five-year evolution of drug prescribing in a university adult intensive care unit

Introduction: Drug prescription is difficult in ICUs as prescribers are many, drugs expensive and decisions complex. In our ICU, specialist clinicians (SC) are entitled to prescribe a list of specific drugs, negotiated with intensive care physicians (ICP). The objective of this investigation was to assess the 5-year evolution of quantity and costs of drug prescription in our adult ICU and identify the relative costs generated by ICP or SC. Methods: Quantities and costs of drugs delivered on a quarterly basis to the adult ICU of our hospital between 2004 and 2008 were extracted from the pharmacy database by ATC code, an international five-level classification system. Within each ATC first level, drugs with either high level of consumption, high costs or large variations in quantities and costs were singled out and split by type of prescriber, ICP or SC. Cost figures used were drug purchase prices by the hospital pharmacy. Results: Over the 5-year period, both quantities and costs of drugs increased, following a nonsteady, nonparallel pattern. Four ATC codes accounted for 80% of both quantities and costs, with ATC code B (blood and haematopoietic organs) amounting to 63% in quantities and 41% in costs, followed by ATC code J (systemic anti-infective, 20% of the costs), ATC code N (nervous system, 11% of the costs) and ATC code C (cardiovascular system, 8% of the costs). Prescription by SC amounted to 1% in drug quantities, but 19% in drug costs. The rate of increase in quantities and costs was seven times larger for ICP than for SC (Figure 1 overleaf ). Some peak values in costs and quantities were related to a very limited number of patients. Conclusions: A 5-year increase in quantities and costs of drug prescription in an ICU is a matter of concern. Rather unexpectedly, total costs and cost increases were generated mainly by ICP. A careful follow-up is necessary to try influencing this evolution through an institutional policy co-opted by all professional categories involved in the process.

Maternal coping, appraisals and adjustment following diagnosis of fetal anomaly.

OBJECTIVE: So far, associations between appraisals, maternal adjustment and coping following diagnosis of fetal anomaly have not been investigated in women who continue with their pregnancy. METHOD: This study measured maternal coping and adjustment after and appraisal of a diagnosis of fetal anomaly in 40 mothers who had continued with their pregnancy using a cross-sectional questionnaire design. RESULTS: Based on retrospective reporting, 35% of participants met full diagnostic criteria for post-traumatic stress disorder after having received the diagnosis. Women were significantly more depressed (p < 0.001) and anxious (p < 0.001) and reported significantly less positive affect (p < 0.05) after having received the diagnosis in comparison to the time after childbirth. There were no significant differences between emotion-focused and problem-focused coping. Stressful life events, women's age, number of people providing support and problem-focused coping explained 57.6% of variance in anxiety and depression after childbirth. Satisfaction with social support, emotion-focused coping and problem-focused coping significantly explained 40.6% of variance in positive affect after childbirth. CONCLUSION: Following a prenatal diagnosis and for the remainder of their pregnancy, particular attention should be paid to older mothers, those experiencing additional stressful life events and those who are socially isolated, as these women may experience greater distress after childbirth.

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study).

To assess the associations between alcohol consumption and cytokine levels (interleukin-1beta - IL-1β; interleukin-6 - IL-6 and tumor necrosis factor-α - TNF-α) in a Caucasian population. Population sample of 2884 men and 3201 women aged 35-75. Alcohol consumption was categorized as nondrinkers, low (1-6 drinks/week), moderate (7-13/week) and high (14+/week). No difference in IL-1β levels was found between alcohol consumption categories. Low and moderate alcohol consumption led to lower IL-6 levels: median (interquartile range) 1.47 (0.70-3.51), 1.41 (0.70-3.32), 1.42 (0.66-3.19) and 1.70 (0.83-4.39) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.01, but this association was no longer significant after multivariate adjustment. Compared to nondrinkers, moderate drinkers had the lowest odds (Odds ratio=0.86 (0.71-1.03)) of being in the highest quartile of IL-6, with a significant (p<0.05) quadratic trend. Low and moderate alcohol consumption led to lower TNF-α levels: 2.92 (1.79-4.63), 2.83 (1.84-4.48), 2.82 (1.76-4.34) and 3.15 (1.91-4.73) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.02, and this difference remained borderline significant (p=0.06) after multivariate adjustment. Moderate drinkers had a lower odds (0.81 [0.68-0.98]) of being in the highest quartile of TNF-α. No specific alcoholic beverage (wine, beer or spirits) effect was found. Moderate alcohol consumption is associated with lower levels of IL-6 and (to a lesser degree) of TNF-α, irrespective of the type of alcohol consumed. No association was found between IL-1β levels and alcohol consumption.

Endocrine response and perceived stress test during an experimental challenge task in adult survivors of a childhood cancer.

BACKGROUND: Although long-term implications of cancer in childhood or adolescence with regard to medical conditions are well documented, the impact on mental health and on response to stress, which may be an indicator of psychological vulnerability, is not yet well understood. In this study, psychological and physiological responses to stress were examined.¦PROCEDURE: Fifty-three participants aged 18-39 years (n = 25 survivors of childhood or adolescence cancer, n = 28 controls) underwent an experimental stress test, the Trier Social Stress Test (TSST). Participants were asked to provide repeated evaluations of perceived stress on visual-analogical scales and blood samples were collected before and after the TSST to measure plasma cortisol.¦RESULTS: The psychological perception of stress was not different between the two groups. However, the cancer survivors group showed a higher global plasma cortisol level as well as higher amplitude in the response to the TSST. The global cortisol level in cancer survivors was increased when depression symptoms were present. The subjective perception of stress and the plasma cortisol levels were only marginally correlated in both groups.¦CONCLUSIONS: It is suggested that the exposure to a life-threatening experience in childhood/adolescence increases the endocrine response to stress, and that the presence of depressive symptoms is associated with an elevation of plasma cortisol levels. A better knowledge of these mechanisms is important given that the dysregulations of the stress responses may cause psychological vulnerability. Pediatr Blood Cancer 2012; 59: 138-143. © 2011 Wiley Periodicals, Inc.

Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.

BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. RESULTS: Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03). CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

Synapse formation on adult-born hippocampal neurons.

It is now widely accepted that adult neurogenesis plays a fundamental role in hippocampal function. Neurons born in the adult dentate gyrus of the hippocampus undergo a series of events before they fully integrate in the network and eventually become undistinguishable from neurons born during embryogenesis. Adult hippocampal neurogenesis is strongly regulated by neuronal activity and neurotransmitters, and the synaptic integration of adult-born neurons occurs in discrete steps, some of which are very different from perinatal synaptogenesis. Here, we review the current knowledge on the development of the synaptic input and output of neurons born in the adult hippocampus, from the stem/progenitor cell to the fully mature neuron. We also provide insight on the regulation of adult neurogenesis by some neurotransmitters and discuss some specificities of the integration of new neurons in an adult environment. The understanding of the mechanisms regulating the synaptic integration of adult-born neurons is not only crucial for our understanding of brain plasticity, but also provides a framework for the manipulation and monitoring of endogenous adult neurogenesis as well as grafted cells, for potential therapeutic applications.

Genome-wide association analysis identifies 20 loci that influence adult height.

Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.

Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.