Lithium and boron in calcified tissues of vicuna and its relation to the chronic exposure by water ingestion in the Andean lithium triangle

Vicuna is a wild, endangered species of Andean camelid living in the hyperarid Andean plateau. In the central part of the plateau, the Lithium Triangle defines a zone with lithium‐rich salt pans. Brine pools naturally form within the salt pans, and the adaptation strategy of vicuna consists of drinking from brine pools. Together with reporting the first chemical data on vicuna bones and teeth, we analyzed lithium, boron, and arsenic in water and brines, with the aim of assessing their relation to chronic exposure by water ingestion. We collected and analyzed bones of vicuna specimens lying in an Andean salt pan, together with brine and water samples. Brine and water samples are highly saline and contain large amounts of lithium, boron, and arsenic. Lithium (13.50–40 mg kg–1 ) and boron (40–46.80 mg kg–1 ), but not arsenic, were found in the vicuna bones and teeth. Based on our results and on previously reported data on human tissues in the Andes, we conducted statistical assessments of the relationships between lithium and boron in body tissues and water samples, and discuss their environmental significance in the context of the Lithium Triangle.Fil: López Steinmetz, Romina Lucrecia. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; Argentina. Universidad Nacional de Jujuy. Instituto de Geología Minera; ArgentinaFil: Fong, Shao Bing. University of Melbourne; AustraliaFil: Boyer, Emile. Universite de Rennes I; FranciaFil: López Steinmetz, Lorena Cecilia. Universidad Nacional de Córdoba. Instituto de Investigaciones Psicológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Psicológicas; ArgentinaFil: Tejerina, Norberto Elio. Universidad Nacional de Jujuy. Instituto de Geología Minera; ArgentinaFil: Meuric, Vincent. Universite de Rennes I; Franci

SdrF, a Staphylococcus epidermidis Surface Protein, Contributes to the Initiation of Ventricular Assist Device Driveline–Related Infections

Staphylococcus epidermidis remains the predominant pathogen in prosthetic-device infections. Ventricular assist devices, a recently developed form of therapy for end-stage congestive heart failure, have had considerable success. However, infections, most often caused by Staphylococcus epidermidis, have limited their long-term use. The transcutaneous driveline entry site acts as a potential portal of entry for bacteria, allowing development of either localized or systemic infections. A novel in vitro binding assay using explanted drivelines obtained from patients undergoing transplantation and a heterologous lactococcal system of surface protein expression were used to identify S. epidermidis surface components involved in the pathogenesis of driveline infections. Of the four components tested, SdrF, SdrG, PIA, and GehD, SdrF was identified as the primary ligand. SdrF adherence was mediated via its B domain attaching to host collagen deposited on the surface of the driveline. Antibodies directed against SdrF reduced adherence of S. epidermidis to the drivelines. SdrF was also found to adhere with high affinity to Dacron, the hydrophobic polymeric outer surface of drivelines. Solid phase binding assays showed that SdrF was also able to adhere to other hydrophobic artificial materials such as polystyrene. A murine model of infection was developed and used to test the role of SdrF during in vivo driveline infection. SdrF alone was able to mediate bacterial adherence to implanted drivelines. Anti-SdrF antibodies reduced S. epidermidis colonization of implanted drivelines. SdrF appears to play a key role in the initiation of ventricular assist device driveline infections caused by S. epidermidis. This pluripotential adherence capacity provides a potential pathway to infection with SdrF-positive commensal staphylococci first adhering to the external Dacron-coated driveline at the transcutaneous entry site, then spreading along the collagen-coated internal portion of the driveline to establish a localized infection. This capacity may also have relevance for other prosthetic device–related infections

Proportional Relations Between Systolic, Diastolic and Mean Pulmonary Artery Pressure are Explained by Vascular Properties

Recently, it was shown that proportional relationships exist between systolic, diastolic and mean pulmonary artery pressure (Psys, Pdia and Pmean) and that they are maintained under various conditions in both health and disease. An arterial-ventricular interaction model was used to study the contribution of model parameters to the ratios Psys/Pmean, and Pdia/Pmean. The heart was modeled by a time-varying elastance function, and the arterial system by a three-element windkessel model consisting of peripheral resistance, Rp, arterial compliance Ca, and pulmonary artery characteristic impedance Z0. Baseline model parameters were estimated in control subjects and compared to values estimated in patients with pulmonary hypertension. Results indicate that experimentally derived ratios Psys/Pmean and Pdia/Pmean could be accurately reproduced using our model (1.59 and 0.61 vs. 1.55 and 0.64, respectively). Sensitivity analysis showed that the (empirical) constancy of Psys/Pmean and Pdia/Pmean was primarily based on the inverse hyperbolic relation between total vascular resistance (RT; calculated as Rp + Z0) and Ca, (i.e. constant RTCa product). Of the cardiac parameters, only heart rate affected the pressure ratios, but the contribution was small. Therefore, we conclude that proportional relations between systolic, diastolic and mean pulmonary artery pressure result from the constancy of RTCa thus from pulmonary arterial properties, with only little influence of heart rate

Rules of Engagement: Journalists’ attitudes to industry influence in health news reporting.

Health-related industries use a variety of methods to influence health news, including the formation and maintenance of direct relationships with journalists. These interactions have the potential to subvert news reporting such that it comes to serve the interests of industry in promoting their products, rather than the public interest in critical and accurate news and information. Here we report the findings of qualitative interviews conducted in Sydney, Australia, in which we examined journalists’ experiences of, and attitudes towards, their relationships with health-related industries. Participants’ belief in their ability to manage industry influence and their perceptions of what it means to be unduly influenced by industry raise important concerns relating to the psychology of influence and the realities of power relationships between industry and journalists. The analysis also indicates ways in which concerned academics and working journalists might establish more fruitful dialogue regarding the role of industry in health-related news and the extent to which increased regulation of journalist-industry relationships might be needed.NHMR

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

Validation of a blood protein signature for non-small cell lung cancer

Background: CT screening for lung cancer is effective in reducing mortality, but there are areas of concern, including a positive predictive value of 4% and development of interval cancers. A blood test that could manage these limitations would be useful, but development of such tests has been impaired by variations in blood collection that may lead to poor reproducibility across populations. Results: Blood-based proteomic profiles were generated with SOMAscan technology, which measured 1033 proteins. First, preanalytic variability was evaluated with Sample Mapping Vectors (SMV), which are panels of proteins that detect confounders in protein levels related to sample collection. A subset of well collected serum samples not influenced by preanalytic variability was selected for discovery of lung cancer biomarkers. The impact of sample collection variation on these candidate markers was tested in the subset of samples with higher SMV scores so that the most robust markers could be used to create disease classifiers. The discovery sample set (n = 363) was from a multi-center study of 94 non-small cell lung cancer (NSCLC) cases and 269 long-term smokers and benign pulmonary nodule controls. The analysis resulted in a 7-marker panel with an AUC of 0.85 for all cases (68% adenocarcinoma, 32% squamous) and an AUC of 0.93 for squamous cell carcinoma in particular. This panel was validated by making blinded predictions in two independent cohorts (n = 138 in the first validation and n = 135 in the second). The model was recalibrated for a panel format prior to unblinding the second cohort. The AUCs overall were 0.81 and 0.77, and for squamous cell tumors alone were 0.89 and 0.87. The estimated negative predictive value for a 15% disease prevalence was 93% overall and 99% for squamous lung tumors. The proteins in the classifier function in destruction of the extracellular matrix, metabolic homeostasis and inflammation. Conclusions: Selecting biomarkers resistant to sample processing variation led to robust lung cancer biomarkers that performed consistently in independent validations. They form a sensitive signature for detection of lung cancer, especially squamous cell histology. This non-invasive test could be used to improve the positive predictive value of CT screening, with the potential to avoid invasive evaluation of nonmalignant pulmonary nodules

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE-Glycated hemoglobin (HbA(1c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA(1c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA(1c) levels.RESEARCH DESIGN AND METHODS-We studied associations with HbA(1c) in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA(1c) loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening.RESULTS-Ten loci reached genome-wide significant association with HbA(1c), including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 x 10(-26)), HFE (rs1800562/P = 2.6 x 10(-20)), TMPRSS6 (rs855791/P = 2.7 x 10(-14)), ANK1 (rs4737009/P = 6.1 x 10(-12)), SPTA1 (rs2779116/P = 2.8 x 10(-9)) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 x 10(-9)), and four known HbA(1c) loci: HK1 (rs16926246/P = 3.1 x 10(-54)), MTNR1B (rs1387153/P = 4.0 X 10(-11)), GCK (rs1799884/P = 1.5 x 10(-20)) and G6PC2/ABCB11 (rs552976/P = 8.2 x 10(-18)). We show that associations with HbA(1c) are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (%HbA(1c)) difference between the extreme 10% tails of the risk score, and would reclassify similar to 2% of a general white population screened for diabetes with HbA(1c).CONCLUSIONS-GWAS identified 10 genetic loci reproducibly associated with HbA(1c). Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA(1c) levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA(1c) Diabetes 59: 3229-3239, 201

Recovery of a US Endangered Fish

BACKGROUND: More fish have been afforded US Endangered Species Act protection than any other vertebrate taxonomic group, and none has been designated as recovered. Shortnose sturgeon (Acipenser brevirostrum) occupy large rivers and estuaries along the Atlantic coast of North America, and the species has been protected by the US Endangered Species Act since its enactment. METHODOLOGY/PRINCIPAL FINDINGS: Data on the shortnose sturgeon in the Hudson River (New York to Albany, NY, USA) were obtained from a 1970s population study, a population and fish distribution study we conducted in the late 1990s, and a fish monitoring program during the 1980s and 1990s. Population estimates indicate a late 1990s abundance of about 60,000 fish, dominated by adults. The Hudson River population has increased by more than 400% since the 1970s, appears healthy, and has attributes typical for a long-lived species. Our population estimates exceed the government and scientific population recovery criteria by more than 500%, we found a positive trend in population abundance, and key habitats have remained intact despite heavy human river use. CONCLUSIONS/SIGNIFICANCE: Scientists and legislators have called for changes in the US Endangered Species Act, the Act is being debated in the US Congress, and the Act has been characterized as failing to recover species. Recovery of the Hudson River population of shortnose sturgeon suggests the combination of species and habitat protection with patience can yield successful species recovery, even near one of the world's largest human population centers

Is Cardiorespiratory Fitness Related to Cardiometabolic Health and All-Cause Mortality Risk in Patients with Coronary Heart Disease? A CARE CR Study

Background: Higher cardiorespiratory fitness (CRF) is associated with lower morbidity and mortality in patients with coronary heart disease (CHD). The mechanisms for this are not fully understood. A more favourable cardiometabolic risk factor profile may be responsible, however few studies have comprehensively evaluated cardiometabolic risk factors in relation to CRF, among patients with CHD. Objective: To explore differences in cardiometabolic risk and 5-year all-cause mortality risk in patients with CHD who have low, moderate, and high levels of CRF. Methods: Patients with CHD underwent maximal cardiopulmonary exercise testing (CPET), echocardiogram, carotid intima-media thickness measurement, spirometry, and dual X-ray absorptiometry assessment. Full blood count, biochemical lipid pro-files, high sensitivity (hs)- C-reactive protein and NT-proBNP were analysed. Pa-tients were defined as having low, moderate, or high CRF based on established prognostic thresholds. Results: 70 patients with CHD (age 63.1 ± 10.0 years, 86% male) were recruited. Patients with low CRF had a lower ventilatory anaerobic threshold, peak oxygen pulse, post-exercise heart rate recovery and poor ventilatory efficiency. The low CRF group also had higher NT pro-BNP, hs-CRP, non-fasting glucose concentrations and lower haemoglobin and haematocrit. Five-year mortality risk (CALIBER risk score) was also greatest in the lowest CRF group (14.9%). Conclusion: Practitioners should interpret low CRF as an important clinical risk factor associated with adverse cardiometabolic health and poor prognosis. Study registry; researchregistry.com (researchregistry3548). Key Words: Coronary Heart Disease, Cardiac Rehabilitation, Cardiometabolic Health, Exercise Training, Atherosclerosis, VO2peak, Maximal Cardiopulmonary Exercise Testing, Caliber 5-year ris

A web-accessible computer program for calculating electrical potentials and ion activities at cell-membrane surfaces

Increasing evidence indicates that plant responses to ions (uptake/transport, inhibition, and alleviation of inhibition) are dependent upon ion activities at the outer surface of root-cell plasma membranes (PMs) rather than activities in the bulk-phase rooting medium