Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD

Background: It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8.Results: Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates. Conclusion: The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.

Prevalence of inflammatory bowel disease in the canton of Vaud (Switzerland) : a population-based cohort study

Abstract : Background and aims: Because of the changing epidemiology of Inflammatory Bowel Diseases (IBD), we set out to characterize the population-based prevalence of Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of Switzerland. Methods: Adult IBD patients were identified by across-matched review of histological, hospital and gastroenterologist files throughout a geographical defined population (Canton of Vaud). Demographic factors statistically significantly associated with prevalence were evaluated using a stepwise Poisson regression analysis. Results were compared to IBD prevalence rates in other population-based studies and time trends were performed, based on a systematic literature review. Results: Age and sex-adjusted prevalence rates were 205.7 IBD (100.7 CD and 105.0 UC) cases per 10,5 inhabitants. Among 1016 IBD patients (519 CD and 497 UC), females outnumbered males in CD (p<0.001), but males were more represented in elderly UC patients (p=0.008). Thus, being a mate was statistically associated with UC (Relative Risk (RR) 1.25; p=0.013), whereas being a female was associated with CD (RR 1.27; p=0.007). Living in an urban zone was associated with both CD and UC (RR 1.49; p<0.001, 1.63; p<0.001, respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4% (95%CI, 2.1%-2.8%; p<0.001) and 3.6% (95%CI, 3.1%-4.1%; p<0.001) per annum were found in industrialised countries. Résumé de synthèse : 1. Introduction : Étant donné l'évolution constante des donnés épidémiologiques sur les maladies inflammatoires chroniques de l'intestin (MICI), nous avons recherché à caractériser la prévalence de la maladie de Crohn (MC) et de la colite ulcéreuse (CU) dans une population définie de la Suisse. 2. Méthodes : Nous avons identifiés, dans une population délimitée au Canton de Vaud, les patients adultes atteints de maladies inflammatoires de l'intestin en regroupant les données histologiques et médicales disponibles à l'hôpital et au cabinet du gastroentérologue. Pour nos analyses, nous avons utilisé la méthode de la régression de Poisson afin d'identifier les facteurs démographiques significativement liés avec la prévalence. Ensuite, nos résultats ont été comparés aux valeurs de prévalence des MICI issues d'autres études de population (revue systématique de la littérature) afin de dégager les tendances de leur évolution au cours du temps. 3. Résultats : La prévalence des MICI pondérée selon l'âge et le sexe était de 205.7 cas (100.7 MC et 105.0 CU) pour 10,5 habitants. Parmi les 1016 patients identifiés (519 MC et 497 CU), les femmes étaient plus représentées que les hommes dans la MC (P<0.0001), alors que la proportion d'hommes dépassait celle des femmes chez les patients âgés atteints de CU (p=0.008). Par conséquent, le fait d'être un homme était statistiquement associé à la CU (Risque relatif (RR) 1.25, p=0.013), et celui d'être une femme était associé à la MC (RR 1.27 ; p=0.007). L'étude a également montré qu'habiter en zone urbaine était significativement associé avec les deux types de MICI (RR (MC) 1.49; p<0.001, (CU) 1.63; p<0.001). Enfin, il a été mis en évidence dans les pays industrialisés, entre 1960 et 2005, une augmentation annuelle des taux de prévalences de 2.4% (95% IC, 2.1 %-2.8% ; p<0.001) pour la MC et de 3.6% (95% IC, 3.1 %-4.1 % ; p<0.001) pour la CU. 4. Conclusion : L'extrapolation de nos données au niveau Suisse fournit une estimation de 12 000 cas de MICI pour le pays soit 1 cas pour 500 habitants. Notre étude contribue également à démontrer une augmentation de la prévalence des MICI en Europe.

Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study.

BACKGROUND: The incidence and outcomes of respiratory viral infections in lung transplant recipients (LTR) are not well defined. The objective of this prospective study conducted from June 2008 to March 2011 was to characterise the incidence and outcomes of viral respiratory infections in LTR. METHODS: Patients were seen in three contexts: study-specific screenings covering all seasons; routine post-transplantation follow-up; and emergency visits. Nasopharyngeal specimens were collected systematically and bronchoalveolar lavage (BAL) was performed when clinically indicated. All specimens underwent testing with a wide panel of molecular assays targeting respiratory viruses. RESULTS: One hundred and twelve LTR had 903 encounters: 570 (63%) were screening visits, 124 (14%) were routine post-transplantation follow-up and 209 (23%) were emergency visits. Respiratory viruses were identified in 174 encounters, 34 of these via BAL. The incidence of infection was 0.83 per patient-year (95% CI 0.45 to 1.52). The viral infection rates upon screening, routine and emergency visits were 14%, 15% and 34%, respectively (p<0.001). Picornavirus was identified most frequently in nasopharyngeal (85/140; 60.7%) and BAL specimens (20/34; 59%). Asymptomatic viral carriage, mainly of picornaviruses, was found at 10% of screening visits. Infections were associated with transient lung function loss and high calcineurin inhibitor blood levels. The hospitalisation rate was 50% (95% CI 30% to 70.9%) for influenza and parainfluenza and 16.9% (95% CI 11.2% to 23.9%) for other viruses. Acute rejection was not associated with viral infection (OR 0.4, 95% CI 0.1 to 1.3). CONCLUSIONS: There is a high incidence of viral infection in LTR; asymptomatic carriage is rare. Viral infections contribute significantly to this population's respiratory symptomatology. No temporal association was observed between infection and acute rejection.

Delay of extubation in neonates and children after cardiac surgery: impact of ventilator-associated pneumonia.

OBJECTIVE: This study was undertaken to determine the delay of extubation attributable to ventilator-associated pneumonia (VAP) in comparison to other complications and complexity of surgery after repair of congenital heart lesions in neonates and children. METHODS: Cohort study in a pediatric intensive care unit of a tertiary referral center. All patients who had cardiac operations during a 22-month period and who survived surgery were eligible (n = 272, median age 1.3 years). Primary outcome was time to successful extubation. Primary variable of interest was VAP Surgical procedures were classified according to complexity. Cox proportional hazards models were calculated to adjust for confounding. Potential confounders comprised other known risk factors for delayed extubation. RESULTS: Median time to extubation was 3 days. VAP occurred in 26 patients (9.6%). The rate of VAP was not associated with complexity of surgery (P = 0.22), or cardiopulmonary bypass (P = 0.23). The adjusted analysis revealed as further factors associated with delayed extubation: other respiratory complications (n = 28, chylothorax, airway stenosis, diaphragm paresis), prolonged inotropic support (n = 48, 17.6%), and the need for secondary surgery (n = 51, 18.8%; e.g., re-operation, secondary closure of thorax). Older age promoted early extubation. The median delay of extubation attributable to VAP was 3.7 days (hazards ratio HR = 0.29, 95% CI 0.18-0.49), exceeding the effect size of secondary surgery (HR = 0.48) and other respiratory complications (HR = 0.50). CONCLUSION: VAP accounts for a major delay of extubation in pediatric cardiac surgery.

The Toarcian in the Subbetic basin (southern Spain): Bio-events (ammonite and calcareous nannofossils) and carbon-isotope stratigraphy

A detailed carbon-isotope stratigraphic study for the uppermost Pliensbachian lowermost Aalenian interval in the Median Subbetic palaeogeographic domain (External zones of the Betic Cordillera, southern Spain) has been carried out. During the Early Jurassic, the Median Subbetic, which represents a typical basin of the Hispanic Corridor connecting the Tethys and the Eastern Pacific, was located in the westernmost Tethys. The analyzed sections encompass the entire Toarcian stage as represented in the southern Iberian palaeomargin. Rocks are mainly rhythmic sequences of grey marls and marly limestones containing a rich ammonite fauna, nannofossils, and benthic foraminifers-all these provide an accurate biostratigraphic control. The lower and upper Toarcian boundaries are well represented in some of these sections and therefore represent optimal sites to link the carbon-isotope curves to ammonite zones, and to nannofossil events. delta C-13 values of bulk carbonates from the different localities of the Subbetic basin have similar variations from the uppermost Pliensbachian to the lowermost Aalenian, suggesting changes in the original DIC carbon isotope composition along the Hispanic corridor. The transition from Pliensbachian to Toarcian is marked by increasing delta C-13 values from similar to 12 to 2.0 parts per thousand, interrupted in the Serpentinum Zone by a negative shift concomitant with the Toarcian oceanic anoxic event (T-OAE), with the major ammonite extinction event of the Toarcian, and an important turnover of calcareous nannoplankton. The negative shift observed in the Serpentinum Zone confirms the global perturbation of the carbon cycling documented along the Tethys and the palaeo-Pacific in organic material and in marine carbonates. However, the amplitude of the negative excursion (similar to - 1.5 parts per thousand) is not compatible with an isotopic homogeneous seawater DIC and/or CO2 atmospheric reservoirs. The interval from the middle to the top of the Toarcian delta C-13 shows relatively constant values, minor ammonite turnovers, and is associated with increasing diversity of calcareous nannoplankton. (c) 2012 Elsevier B.V. All rights reserved.

The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1-infected patients treated with Peg-IFN-alfa-2a and ribavirin.

Summary.  Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1-infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of ≥2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, ≥0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.

Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors.

AIMS: Common carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures. METHODS AND RESULTS: We combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)]. CONCLUSION: We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.

High incidence of childhood hemolytic uremic syndrome in Switzerland is associated with indicators of livestock farming intensity

Background: Hemolytic-uremic syndrome (HUS) is a multisystem disorder associated with significant morbidity and mortality. Typically, HUS is preceded by an episode of (bloody) diarrhea mostly due to Shiga-toxin (Stx) producing Escherichia coli (STEC). The main reservoir for STEC is the intestine of healthy ruminants, mostly cattle, and recent studies have revealed an association between indicators of livestock density and human STEC infection or HUS, respectively. Nationwide data on HUS in Switzerland have been established through the Swiss Pediatric Surveillance Unit (SPSU) [Schifferli et al. Eur J Pediatr. 2010; 169:591-8]. Aims: Analysis of age-specific incidence rate of childhood HUS and possible association of Shiga-toxin associated HUS (Stx-HUS) with indicators of livestock farming intensity. Methods: Epidemiological and ecological analysis based on the SPSU data (1997-2003) and the database of the Swiss Federal Statistical Office (data on population and agriculture). Results: One hundred-fourteen cases were registered, 88% were ≤5 years old. The overall annual incidence rate was 1.42 (0.60-1.91) and 4.23 (1.76-6.19) per 100000 children ≤5 and ≤16 years, respectively (P = 0.005). Stx-HUS was more frequent compared to cases not associated with STEC (P = 0.002). The incidence rate for Stx-HUS was 3.85 (1.76-5.65) in children ≤5, compared to 0.27 (0.00-0.54) per 100'000 children 5-16 years (P = 0.002), respectively. The incidence rate of cases not associated with STEC infection did not significantly vary with age (P = 0.107). Compared to data from Scotland, Canada, Ireland, Germany, England, Australia, Italy, and Austria the annual incidence rate of HUS in young children is highest in Switzerland. Ecological analysis revealed strong association between the incidence rate of Stx-HUS and indicators of rural occupation (agricultural labourer / population, P = 0.030), farming intensity (livestock breeding farms / population, P = 0.027) and cattle density (cattle / cultivated area, P = 0.013). Conclusions: Alike in other countries, HUS in Switzerland is mostly associated with STEC infection and affects predominantly young children. However, the incidence rate is higher compared to countries abroad and is significantly correlated with indicators of livestock farming intensity. The present data support the impact of direct and indirect contact with animals or fecal contaminants in transmission of STEC to humans.

Caution on the storage of waters and aqueous solutions in plastic containers for hydrogen and oxygen stable isotope analysis

RATIONALE The choice of containers for storage of aqueous samples between their collection, transport and water hydrogen (2H) and oxygen (18O) stable isotope analysis is a topic of concern for a wide range of fields in environmental, geological, biomedical, food, and forensic sciences. The transport and separation of water molecules during water vapor or liquid uptake by sorption or solution and the diffusive transport of water molecules through organic polymer material by permeation or pervaporation may entail an isotopic fractionation. An experiment was conducted to evaluate the extent of such fractionation. METHODS Sixteen bottle-like containers of eleven different organic polymers, including low and high density polyethylene (LDPE and HDPE), polypropylene (PP), polycarbonate (PC), polyethylene terephthalate (PET), and perfluoroalkoxy-Teflon (PFA), of different wall thickness and size were completely filled with the same mineral water and stored for 659?days under the same conditions of temperature and humidity. Particular care was exercised to keep the bottles tightly closed and prevent loss of water vapor through the seals. RESULTS Changes of up to +5 parts per thousand for d2H values and +2.0 parts per thousand for d18O values were measured for water after more than 1?year of storage within a plastic container, with the magnitude of change depending mainly on the type of organic polymer, wall thickness, and container size. The most important variations were measured for the PET and PC bottles. Waters stored in glass bottles with Polyseal (TM) cone-lined PP screw caps and thick-walled HDPE or PFA containers with linerless screw caps having an integrally molded inner sealing ring preserved their original d2H and d18O values. The carbon, hydrogen, and oxygen stable isotope compositions of the organic polymeric materials were also determined. CONCLUSIONS The results of this study clearly show that for precise and accurate measurements of the water stable isotope composition in aqueous solutions, rigorous sampling and storage procedures are needed both for laboratory standards and for unknown samples. Copyright (c) 2012 John Wiley & Sons, Ltd.

CT arthrography of the glenohumeral joint: CT fluoroscopy versus conventional CT and fluoroscopy--comparison of image-guidance techniques.

PURPOSE: To compare examination time with radiologist time and to measure radiation dose of computed tomographic (CT) fluoroscopy, conventional CT, and conventional fluoroscopy as guiding modalities for shoulder CT arthrography. MATERIALS AND METHODS: Glenohumeral injection of contrast material for CT arthrography was performed in 64 consecutive patients (mean age, 32 years; age range, 16-74 years) and was guided with CT fluoroscopy (n = 28), conventional CT (n = 14), or conventional fluoroscopy (n = 22). Room times (arthrography, room change, CT, and total examination times) and radiologist times (time the radiologist spent in the fluoroscopy or CT room) were measured. One-way analysis of variance and Bonferroni-Dunn posthoc tests were performed for comparison of mean times. Mean effective radiation dose was calculated for each method with examination data, phantom measurements, and standard software. RESULTS: Mean total examination time was 28.0 minutes for CT fluoroscopy, 28.6 minutes for conventional CT, and 29.4 minutes for conventional fluoroscopy; mean radiologist time was 9.9 minutes, 10.5 minutes, and 9.0 minutes, respectively. These differences were not statistically significant. Mean effective radiation dose was 0.0015 mSv for conventional fluoroscopy (mean, nine sections), 0.22 mSv for CT fluoroscopy (120 kV; 50 mA; mean, 15 sections), and 0.96 mSv for conventional CT (140 kV; 240 mA; mean, six sections). Effective radiation dose can be reduced to 0.18 mSv for conventional CT by changing imaging parameters to 120 kV and 100 mA. Mean effective radiation dose of the diagnostic CT arthrographic examination (140 kV; 240 mA; mean, 25 sections) was 2.4 mSv. CONCLUSION: CT fluoroscopy and conventional CT are valuable alternative modalities for glenohumeral CT arthrography, as examination and radiologist times are not significantly different. CT guidance requires a greater radiation dose than does conventional fluoroscopy, but with adequate parameters CT guidance constitutes approximately 8% of the radiation dose.

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Origin of mineralizing fluids of the sediment-hosted Navachab gold mine, Namibia: Constraints from stable (O, H, C, S) isotopes

The Navachab gold mine in the Damara belt of central Namibia is characterized by a polymetallic Au-Bi-As-Cu-Ag ore assemblage, including pyrrhotite, chalcopyrite, sphalerite, arsenopyrite, bismuth, gold, bismuthinite, and bismuth tellurides. Gold is hosted by quartz sulfide veins and semimassive sulfide lenses that are developed in a near-vertical sequence of shelf-type metasedimentary rocks, including marble, calcsilicate rock, and biotite schist. The sequence has been intruded by abundant syntectonic lamprophyre, aplite, and pegmatite dikes, documenting widespread igneous activity coeval with mineralization. The majority of quartz from the veins has delta(18)O values of 14 to 15 per mil (V-SMOW). The total variations in delta(18)O values of the biotite schist and calcsilicate rock are relatively small (12-14 parts per thousand), whereas the marble records steep gradients in delta(18)O values (17-21 parts per thousand), the lowest values being recorded at the vein margins. Despite this, there is no correlation between delta(18)O and delta(13)C values and the carbonate content of the rocks, indicating that fluid-rock interaction alone cannot explain the isotopic gradients. In addition, the marble records increased delta(13)C values at the contact to the veins, possibly related to a change in the physicochemical conditions during fluid-rock interaction. Gold is interpreted to have precipitated in equilibrium with metamorphic find (delta(18)O 12-14 parts per thousand; delta D = -40 to -60 parts per thousand) at peak metamorphic conditions of ca. 550 degrees C and 2 kbars, consistent with isotopic fractionations between coexisting calcite, garnet, and clinopyroxene in the alteration halos. The most likely source of the mineralizing fluid was a midcrustal fluid in equilibrium with the Damaran metapelites that underwent prograde metamorphism at amphibolite- to granulite-facies grades. Although there is no isotopic evidence for the contribution of magmatic fluids, they may have been important in contributing to the overall hydraulic regime and high apparent geothermal gradients (ca. 80 degrees C/km(-1)) in the mine area.

Inverse association between circulating vitamin D and mortality-dependent on sex and cause of death?

BACKGROUND AND AIMS: In various populations, vitamin D deficiency is associated with chronic diseases and mortality. We examined the association between concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and all-cause as well as cause-specific mortality. METHODS AND RESULTS: The study included 3404 participants of the general adult Swiss population, who were recruited between November 1988 and June 1989 and followed-up until the end of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox proportional hazards regression was used to examine the association between 25(OH)D concentration and all-cause and cause-specific mortality adjusting for sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10 ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D concentration was inversely associated with cancer mortality in men (HR = 0.72, 95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93-1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality association. CONCLUSION: 25(OH)D was similarly inversely related to all-cause mortality in men and women. However, we observed opposite effects in women and men with respect to cardiovascular and cancer mortality.

Un programa de atención multidisciplinar al paciente con hepatitis crónica C mejora la eficacia del tratamiento con peginterferon alfa-2a y ribavirina.

La adherencia al tratamiento antiviral de la hepatitis crónica C (HCC) es una variable importante en la obtención de la respuesta viral sostenida (RVS). El objetivo de este trabajo es evaluar el impacto de un programa de atención multidisciplinar (PAM) en la adherencia y eficacia del tratamiento de la HCC. Se incluyeron 447 pacientes tratados con peginterferón-alfa-2a y ribavirina y se clasificaron en tres grupos: grupo control (2003-2004, n=147), grupo PAM (2005-2006, n=131) y grupo Validación-PAM (2007-2009, n=169). La adherencia y los porcentajes de RVS fueron superiores en los pacientes incluidos en los grupos PAM (94.6% y 77.1%) y Validación-PAM (91.7% y 74.6%) en comparación con el grupo control (78.9% y 61.9%) (p<0.05 para todos los casos).

Oxidative and glycogenolytic cCapacities within the developing chick heart.

Cardiac morphogenesis and function are known to depend on both aerobic and anaerobic energy-producing pathways. However, the relative contribution of mitochondrial oxidation and glycogenolysis, as well as the determining factors of oxygen demand in the distinct chambers of the embryonic heart, remains to be investigated. Spontaneously beating hearts isolated from stage 11, 20, and 24HH chick embryos were maintained in vitro under controlled metabolic conditions. O(2) uptake and glycogenolytic rate were determined in atrium, ventricle, and conotruncus in the absence or presence of glucose. Oxidative capacity ranged from 0.2 to 0.5 nmol O(2)/(h.microg protein), did not depend on exogenous glucose, and was the highest in atria at stage 20HH. However, the highest reserves of oxidative capacity, assessed by mitochondrial uncoupling, were found at the youngest stage and in conotruncus, representing 75 to 130% of the control values. At stage 24HH, glycogenolysis in glucose-free medium was 0.22, 0.17, and 0.04 nmol glucose U(h.microg protein) in atrium, ventricle, and conotruncus, respectively. Mechanical loading of the ventricle increased its oxidative capacity by 62% without altering glycogenolysis or lactate production. Blockade of glycolysis by iodoacetate suppressed lactate production but modified neither O(2) nor glycogen consumption in substrate-free medium. These findings indicate that atrium is the cardiac chamber that best utilizes its oxidative and glycogenolytic capacities and that ventricular wall stretch represents an early and major determinant of the O(2) uptake. Moreover, the fact that O(2) and glycogen consumptions were not affected by inhibition of glyceraldehyde-3-phosphate dehydrogenase provides indirect evidence for an active glycerol-phosphate shuttle in the embryonic cardiomyocytes.