Brain natriuretic peptide and NT-proBNP levels reflect pulmonary artery systolic pressure in trekkers at high altitude.

Our objective was to evaluate the utility of the natriuretic peptides BNP (brain natriuretic peptide) and NT-proBNP as markers of pulmonary artery systolic pressure (PASP) in trekkers ascending to high altitude (HA). 20 participants had BNP and NT-proBNP assayed and simultaneous echocardiographic assessment of PASP performed during a trek to 5150 m. PASP increased significantly (p=0.006) with ascent from 24+/-4 to 39+/-11 mm Hg at 5150 m. At 5150 m those with a PASP>/=40 mm Hg (n=8) (versus those with PASP/=400 pg/ml) rise in NT-proBNP at 5150 m (n=4) PASP was significantly higher: 45.9+/-7.5 vs. 32.2+/-6.2 mm Hg (p=0.015). BNP and NT-proBNP may reflect elevated PASP, a central feature of high altitude pulmonary oedema, at HA

Neutrophil gelatinase-associated lipocalin: its response to hypoxia and association with acute mountain sickness.

Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly (P < 0.001) from 68 ± 14 (60-102) at 1300 m to 183 ± 107 (65-519); 143 ± 66 (60-315) and 150 ± 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS

Mechanistic determination of tear film thinning via fitting simplified models to tear breakup

Purpose: To determine whether evaporation, tangential flow, or a combination of the two cause tear film breakup in a variety of instances; to estimate related breakup parameters that cannot be measured in breakup during subject trials; and to validate our procedure against previous work. Methods: Five ordinary differential equation models for tear film thinning were designed that model evaporation, osmosis, and various types of flow. Eight tear film breakup instances of five healthy subjects that were identified in fluorescence images in previous work were fit with these five models. The fitting procedure used a nonlinear least squares optimization that minimized the difference of the computed theoretical fluorescent intensity from the models and the experimental fluorescent intensity from the images. The optimization was conducted over the evaporation rate and up to three flow rate parameters. The smallest norm of the difference was determined to correspond to the model that best explained the tear film dynamics. Results: All of the breakup instances were best fit by models with time-dependent flow. Our optimal parameter values and thinning rate and fluid flow profiles compare well with previous partial differential equation model results in most instances. Conclusion: Our fitting procedure suggests that the combination of the Marangoni effect and evaporation cause most of the breakup instances. Comparison with results from previous work suggests that the simplified models can capture the essential tear film dynamics in most cases, thereby validating this procedure as one that could be used on many other instances.Comment: 28 pages, 11 figures, 6 table

Cancer Biology Data Curation at the Mouse Tumor Biology Database (MTB)

Many advances in the field of cancer biology have been made using mouse models of human cancer. The Mouse Tumor Biology (MTB, &#x22;http://tumor.informatics.jax.org&#x22;:http://tumor.informatics.jax.org) database provides web-based access to data on spontaneous and induced tumors from genetically defined mice (inbred, hybrid, mutant, and genetically engineered strains of mice). These data include standardized tumor names and classifications, pathology reports and images, mouse genetics, genomic and cytogenetic changes occurring in the tumor, strain names, tumor frequency and latency, and literature citations.&#xd;&#xa;&#xd;&#xa;Although primary source for the data represented in MTB is peer-reviewed scientific literature an increasing amount of data is derived from disparate sources. MTB includes annotated histopathology images and cytogenetic assay images for mouse tumors where these data are available from The Jackson Laboratory&#x2019;s mouse colonies and from outside contributors. MTB encourages direct submission of mouse tumor data and images from the cancer research community and provides investigators with a web-accessible tool for image submission and annotation. &#xd;&#xa;&#xd;&#xa;Integrated searches of the data in MTB are facilitated by the use of several controlled vocabularies and by adherence to standard nomenclature. MTB also provides links to other related online resources such as the Mouse Genome Database, Mouse Phenome Database, the Biology of the Mammary Gland Web Site, Festing&#x27;s Listing of Inbred Strains of Mice, the JAX&#xae; Mice Web Site, and the Mouse Models of Human Cancers Consortium&#x27;s Mouse Repository. &#xd;&#xa;&#xd;&#xa;MTB provides access to data on mouse models of cancer via the internet and has been designed to facilitate the selection of experimental models for cancer research, the evaluation of mouse genetic models of human cancer, the review of patterns of mutations in specific cancers, and the identification of genes that are commonly mutated across a spectrum of cancers.&#xd;&#xa;&#xd;&#xa;MTB is supported by NCI grant CA089713

Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews

Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews was conducted. For inclusion, reviews had to compare pregnant women of healthy weight with women with obesity, and measure a health outcome for mother and/or baby. Authors conducted full-text screening, quality assurance using the AMSTAR tool and data extraction steps in pairs. Narrative analysis of the 22 reviews included show gestational diabetes, pre-eclampsia, gestational hypertension, depression, instrumental and caesarean birth, and surgical site infection to be more likely to occur in pregnant women with obesity compared with women with a healthy weight. Maternal obesity is also linked to greater risk of preterm birth, large-for-gestational-age babies, foetal defects, congenital anomalies and perinatal death. Furthermore, breastfeeding initiation rates are lower and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy weight women. These adverse outcomes may result in longer duration of hospital stay, with concomitant resource implications. It is crucial to reduce the burden of adverse maternal and foetal/child outcomes caused by maternal obesity. Women with obesity need support to lose weight before they conceive, and to minimize their weight gain in pregnancy

Strained tetragonal states and Bain paths in metals

Paths of tetragonal states between two phases of a material, such as bcc and fcc, are called Bain paths. Two simple Bain paths can be defined in terms of special imposed stresses, one of which applies directly to strained epitaxial films. Each path goes far into the range of nonlinear elasticity and reaches a range of structural parameters in which the structure is inherently unstable. In this paper we identify and analyze the general properties of these paths by density functional theory. Special examples include vanadium, cobalt and copper, and the epitaxial path is used to identify an epitaxial film as related uniquely to a bulk phase.Comment: RevTeX, 4 pages, 4 figures, submitted to Phys. Rev. Let

Charitable Food Systems' Capacity to Address Food Insecurity: An Australian Capital City Audit.

Australian efforts to address food insecurity are delivered by a charitable food system (CFS) which fails to meet demand. The scope and nature of the CFS is unknown. This study audits the organisational capacity of the CFS within the 10.9 square kilometres of inner-city Perth, Western Australia. A desktop analysis of services and 12 face-to-face interviews with representatives from CFS organisations was conducted. All CFS organisations were not-for⁻profit and guided by humanitarian or faith-based values. The CFS comprised three indirect services (IS) sourcing, banking and/or distributing food to 15 direct services (DS) providing food to recipients. DS offered 30 different food services at 34 locations feeding over 5670 people/week via 16 models including mobile and seated meals, food parcels, supermarket vouchers, and food pantries. Volunteer to paid staff ratios were 33:1 (DS) and 19:1 (IS). System-wide, food was mainly donated and most funding was philanthropic. Only three organisations received government funds. No organisation had a nutrition policy. The organisational capacity of the CFS was precarious due to unreliable, insufficient and inappropriate financial, human and food resources and structures. System-wide reforms are needed to ensure adequate and appropriate food relief for Australians experiencing food insecurity

A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-α

Emerging evidence points to aberrant regulation of translation as a driver of cell transformation in cancer. Given the direct control of translation by tRNA modifications, tRNA modifying enzymes may function as regulators of cancer progression. Here, we show that a tRNA methyltransferase 9‐like (hTRM9L/KIAA1456) mRNA is down‐regulated in breast, bladder, colorectal, cervix and testicular carcinomas. In the aggressive SW620 and HCT116 colon carcinoma cell lines, hTRM9L is silenced and its re‐expression and methyltransferase activity dramatically suppressed tumour growth in vivo. This growth inhibition was linked to decreased proliferation, senescence‐like G0/G1‐arrest and up‐regulation of the RB interacting protein LIN9. Additionally, SW620 cells re‐expressing hTRM9L did not respond to hypoxia via HIF1‐α‐dependent induction of GLUT1. Importantly, hTRM9L‐negative tumours were highly sensitive to aminoglycoside antibiotics and this was associated with altered tRNA modification levels compared to antibiotic resistant hTRM9L‐expressing SW620 cells. Our study links hTRM9L and tRNA modifications to inhibition of tumour growth via LIN9 and HIF1‐α‐dependent mechanisms. It also suggests that aminoglycoside antibiotics may be useful to treat hTRM9L‐deficient tumours.National Institute of Environmental Health Sciences (R01 ES015037)National Institute of Environmental Health Sciences (R01 ES017010)National Institute of Environmental Health Sciences (R21 ES017146)National Institute of Environmental Health Sciences (P30 ES002109)National Cancer Institute (U.S.) (R01 CA109182)National Cancer Institute (U.S.) (U54 CA163131)National Science Foundation (U.S.) (NSF 0922830)NYSTARWestaway Research FundSingapore-MIT Alliance for Research and TechnologySamuel Waxman Cancer Research Foundation Tumour Dormancy ProgramNYSTE