Genome-wide association and functional follow-up reveals new loci for kidney function.

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Pancreatic islet adaptation to fasting is dependent on peroxisome proliferator-activated receptor alpha transcriptional up-regulation of fatty acid oxidation.

The cellular response to fasting and starvation in tissues such as heart, skeletal muscle, and liver requires peroxisome proliferator-activated receptor-alpha (PPARalpha)-dependent up-regulation of energy metabolism toward fatty acid oxidation (FAO). PPARalpha null (PPARalphaKO) mice develop hyperinsulinemic hypoglycemia in the fasting state, and we previously showed that PPARalpha expression is increased in islets at low glucose. On this basis, we hypothesized that enhanced PPARalpha expression and FAO, via depletion of lipid-signaling molecule(s) for insulin exocytosis, are also involved in the normal adaptive response of the islet to fasting. Fasted PPARalphaKO mice compared with wild-type mice had supranormal ip glucose tolerance due to increased plasma insulin levels. Isolated islets from the PPARalpha null mice had a 44% reduction in FAO, normal glucose use and oxidation, and enhanced glucose-induced insulin secretion. In normal rats, fasting for 24 h increased islet PPARalpha, carnitine palmitoyltransferase 1, and uncoupling protein-2 mRNA expression by 60%, 62%, and 82%, respectively. The data are consistent with the view that PPARalpha, via transcriptionally up-regulating islet FAO, can reduce insulin secretion, and that this mechanism is involved in the normal physiological response of the pancreatic islet to fasting such that hypoglycemia is avoided.

Conversion of an administrative record system for compatibility with the ICIDH.

This paper presents an account of considerations relevant to conversion of data in an administrative record system into categories compatible with the ICIDH. Existing information recorded for the Swiss disablement insurance scheme fairly readily generates impairment and disability data relating to the time of first contact with the scheme, and the means for conversion are illustrated. The system does not generate data relevant to handicap.

Free microvascular iliac crest flap for extensive talar necrosis--case report with a 16-year long-term follow up.

Atraumatic osteonecrosis of the talus can be extremely painful and lead to significant functional impairment. Although clinical, radiographic, and demographic characteristics of atraumatic osteonecrosis of the talus have been well documented, the diagnosis is frequently missed or delayed; the most common causes are use of corticosteroids and the presence of immune disorders. Operative treatment of large osteochondral lesions of the talus is difficult because the blood supply is poor in the talar dome. Microvascular reconstruction of the talar dome with iliac crest autografts is a complex but functionally excellent therapeutic option. We present a 48-year-old man, who developed an extensive atraumatic avascular necrosis of the talar dome without collapse. Except for insulin dependent diabetes mellitus no further comorbidities were known. A microvascular iliac crest bone flap was inserted into the talus. A follow-up 16 years postoperatively showed a clinically as well as radiographically stable reconstruction of the talar dome and an excellent mobility of the ankle joint. The AOFAS hindfoot scale had improved from initially 33 points to 100 on the last follow-up. Free microvascular bony reconstruction of the talar dome should not only be considered in younger patients but also for middle aged active patients, since our follow-up shows an excellent long term result. Early reconstruction can prevent collapse of the talar bone.

Traitement chronique de l'hypertension arterielle par un inhibiteur de l'enzyme de conversion de l'angiotensine. [Chronic treatment of hypertension by an inhibitor of angiotensin converting enzyme]

Captopril, or SQ 14,225 an orally active inhibitor of angiotensin-converting enzyme, produced a significant blood pressure reduction in 26 hypertensives. This new drug, alone or combined with a diuretic, has normalized the blood pressure of the 22 patients on long-term treatment.

Catch-up growth strategies differ between body structures: interactions between age and structure-specific growth in wild nestling Alpine swifts

1. Little is known on the occurrence and magnitude of faster than normal (catch-up) growth in response to periods of undernutrition in the wild, and the extent to which different body structures compensate and over what timescales is poorly understood. 2. We investigated catch-up growth in nestling Alpine Swifts, Apus melba, by comparing nestling growth trajectories in response to a naturally occurring 1-week period of inclement weather and undernutrition with growth of nestlings reared in a good year. 3. In response to undernutrition, nestlings exhibited a hierarchy of tissues preservation and compensation, with body mass being restored quickly after the end of the period of undernutrition, acceleration of skeletal growth occurring later in development, and compensation in wing length occurring mostly due to a prolongation of growth and delayed fledging. 4. The effect of undernutrition and subsequent catch-up growth was age-dependent, with older nestlings being more resilient to undernutrition, and in turn having less need to compensate later in the development. 5. This shows that young in a free-living bird population can compensate in body mass and body size for a naturally occurring period of undernutrition, and that the timing and extent of compensation varies with age and between body structures.

3-year follow-up results of bone mineral content and density after a school-based physical activity randomized intervention trial.

BACKGROUND: As an important modifiable lifestyle factor in osteoporosis prevention, physical activity has been shown to positively influence bone mass accrual during growth. We have previously shown that a nine month general school based physical activity intervention increased bone mineral content (BMC) and density (aBMD) in primary school children. From a public health perspective, a major key issue is whether these effects persist during adolescence. We therefore measured BMC and aBMD three years after cessation of the intervention to investigate whether the beneficial short-term effects persisted. METHODS: All children from 28 randomly selected first and fifth grade classes (intervention group (INT): 16 classes, n=297; control group (CON): 12 classes, n=205) who had participated in KISS (Kinder-und Jugendsportstudie) were contacted three years after cessation of the intervention program. The intervention included daily physical education with daily impact loading activities over nine months. Measurements included anthropometry, vigorous physical activity (VPA) by accelerometers, and BMC/aBMD for total body, femoral neck, total hip, and lumbar spine by dual-energy X-ray absorptiometry (DXA). Sex- and age-adjusted Z-scores of BMC or aBMD at follow-up were regressed on intervention (1 vs. 0), the respective Z-score at baseline, gender, follow-up height and weight, pubertal stage at follow-up, previous and current VPA, adjusting for clustering within schools. RESULTS: 377 of 502 (75%) children participated in baseline DXA measurements and of those, 214 (57%) participated to follow-up. At follow-up INT showed significantly higher Z-scores of BMC at total body (adjusted group difference: 0.157 units (0.031-0.283); p=0.015), femoral neck (0.205 (0.007-0.402); p=0.042) and at total hip (0.195 (0.036 to 0.353); p=0.016) and higher Z-scores of aBMD for total body (0.167 (0.016 to 0.317); p=0.030) compared to CON, representing 6-8% higher values for children in the INT. No differences could be found for the remaining bone parameters. For the subpopulation with baseline VPA (n=163), effect sizes became stronger after baseline VPA adjustment. After adjustment for baseline and current VPA (n=101), intervention effects were no longer significant, while effect sizes remained the same as without adjustment for VPA. CONCLUSION: Beneficial effects on BMC of a nine month general physical activity intervention appeared to persist over three years. Part of the maintained effects may be explained by current physical activity.

The Check-Up, November 2013-Jaunary 2014

An update on issues and ideas related to health reform in Iowa Second Story Headline The Check-Up is a monthly health care reform newsletter designed to keep interested Iowans up to date on the progress of health reform initiatives assigned to IDPH.

Résumés actualisés de l'évaluation systématique de l'efficacité d'interventions médicales. [Up-to-date résumés of the systematic evaluation of efficacy of medical interventions]

La Cochrane Library (www.thecochranelibrary.com) est une bibliothèque en ligne répertoriant à ce jour plus de 3000 revues systématiques. Ces revues systématiques sont issues de l'activité continue de plus de 50 groupes de revues de la Collaboration Cochrane (www.cochrane.org ), une organisation à laquelle participent plus de 20 000 personnes dans le monde entier et dont le financement est indépendant de sources pouvant créer un conflit d'intérêt. Le public cible est constitué par les professionnels de la santé, les décideurs en matière sanitaire et le public (patients, consommateurs). En sus de la production et de la diffusion de revues systématiques, la Collaboration Cochrane propose également des activités de formation aux méthodes de la médecine factuelle et des revues systématiques. En Francophonie, de telles formations sont proposées par des partenaires du Réseau francophone Cochrane (www.res_franco.cochrane.org ), dont la coordination est assurée depuis Lausanne par une petite équipe basée à l'Institut universitaire de médecine sociale et préventive (IUMSP). [Extrait]

Loss to follow-up in an international, multicentre observational study.

OBJECTIVE: The aim of this work was to assess loss to follow-up (LTFU) in EuroSIDA, an international multicentre observational cohort study. METHODS: LTFU was defined as no follow-up visit, CD4 cell count measurement or viral load measurement after 1 January 2006. Poisson regression was used to describe factors related to LTFU. RESULTS: The incidence of LTFU in 12 304 patients was 3.72 per 100 person-years of follow-up [95% confidence interval (CI) 3.58-3.86; 2712 LTFU] and varied among countries from 0.67 to 13.35. After adjustment, older patients, those with higher CD4 cell counts, and those who had started combination antiretroviral therapy all had lower incidences of LTFU, while injecting drug users had a higher incidence of LTFU. Compared with patients from Southern Europe and Argentina, patients from Eastern Europe had over a twofold increased incidence of LTFU after adjustment (incidence rate ratio 2.16; 95% CI 1.84-2.53; P<0.0001). A total of 2743 patients had a period of >1 year with no CD4 cell count or viral load measured during the year; 743 (27.1%) subsequently returned to follow-up. CONCLUSIONS: Some patients thought to be LTFU may have died, and efforts should be made to ascertain vital status wherever possible. A significant proportion of patients who have a year with no follow-up visit, CD4 cell count measurement or viral load measurement subsequently return to follow-up.