Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Clinical, Virological and Immunological Features from Patients Infected with Re-Emergent Avian-Origin Human H7N9 Influenza Disease of Varying Severity in Guangdong Province

The second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.Background The second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region. Methods Five patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery. Results Four patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%). Conclusion Expectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.published_or_final_versio

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Rejuvenation of metallic glasses by non-affine thermal strain.

When a spatially uniform temperature change is imposed on a solid with more than one phase, or on a polycrystal of a single, non-cubic phase (showing anisotropic expansion-contraction), the resulting thermal strain is inhomogeneous (non-affine). Thermal cycling induces internal stresses, leading to structural and property changes that are usually deleterious. Glasses are the solids that form on cooling a liquid if crystallization is avoided--they might be considered the ultimate, uniform solids, without the microstructural features and defects associated with polycrystals. Here we explore the effects of cryogenic thermal cycling on glasses, specifically metallic glasses. We show that, contrary to the null effect expected from uniformity, thermal cycling induces rejuvenation, reaching less relaxed states of higher energy. We interpret these findings in the context that the dynamics in liquids become heterogeneous on cooling towards the glass transition, and that there may be consequent heterogeneities in the resulting glasses. For example, the vibrational dynamics of glassy silica at long wavelengths are those of an elastic continuum, but at wavelengths less than approximately three nanometres the vibrational dynamics are similar to those of a polycrystal with anisotropic grains. Thermal cycling of metallic glasses is easily applied, and gives improvements in compressive plasticity. The fact that such effects can be achieved is attributed to intrinsic non-uniformity of the glass structure, giving a non-uniform coefficient of thermal expansion. While metallic glasses may be particularly suitable for thermal cycling, the non-affine nature of strains in glasses in general deserves further study, whether they are induced by applied stresses or by temperature change.This research was supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan, by NSF China and MOST 973 China, and by the Engineering and the Engineering and Physical Sciences Research Council, UK (Materials World Network project). Y.H.S. acknowledges support from a China Scholarship Council (CSC) scholarship.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1467

The geoaccumulation index and enrichment factor of mercury in mangrove sediment of Port Klang, Selangor, Malaysia.

Mangrove areas are important to the ecosystem. One of its crucial functions is as a sink of pollutants, especially metal ions. However, the accumulation of metals in mangrove sediment can generate negative impacts on plant growth, microbial activity, and soil fertility. Apart from that, the severity of the impact is highly influenced by the type of metal found in the sediment and the quality of sediment itself. One of the metals that have adverse effects on the environment is mercury. The objectives of this study are to determine the concentration and distribution of mercury and to assess the enrichment of mercury in Port Klang mangrove sediment by using geoaccumulation index and enrichment factor. Sediment samples were collected from 30 sampling points that cover Langat River and Klang River estuaries, Lumut Straits, Pulau Klang, and Pulau Indah. During sampling, water parameters such as pH, salinity, electrical conductivity, and total dissolved solids were measured in situ, whereas the total mercury in sediment samples was determined at the laboratory using inductively coupled plasma mass spectrometry. In this study, mercury was found to be concentrated along Lumut Strait especially in the mixing zone near the confluence of Langat River and at the jetty to Pulau Ketam. The geoaccumulation index and enrichment factor (calculated using logarithmized data of the reference element) found that three stations were enriched with mercury. In addition, geoaccumulation index was also observed to be more objective compared to enrichment factor whose results were influenced by the concentration of reference element used

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

A role of the Atlantic Ocean in predicting summer surface air temperature over North East Asia?

We assess the ability of the DePreSys3 prediction system to predict the summer (JJAS) surface-air temperature over North East Asia. DePreSys3 is based on a high resolution ocean–atmosphere coupled climate prediction system (~ 60 km in the atmosphere and ~ 25 km in the ocean), which is full-field initialized from 1960 to 2014 (26 start-dates). We find skill in predicting surface-air temperature, relative to a long-term trend, for 1 and 2–5 year leadtimes over North East Asia, the North Atlantic Ocean and Eastern Europe. DePreSys3 also reproduces the interdecadal evolution of surface-air temperature over the North Atlantic subpolar gyre and North East Asia for both lead times, along with the strong warming that occurred in the mid-1990s over both areas. Composite analysis reveals that the skill at capturing interdecadal changes in North East Asia is associated with the propagation of an atmospheric Rossby wave, which follows the subtropical jet and modulates surface-air temperature from Europe to Eastern Asia. We hypothesise that this ‘circumglobal teleconnection’ pattern is excited over the Atlantic Ocean and is related to Atlantic multi-decadal variability and the associated changes in precipitation over the Sahel and the subtropical Atlantic Ocean. This mechanism is robust for the 2–5 year lead-time. For the 1 year lead-time the Pacific Ocean also plays an important role in leading to skill in predicting SAT over Northeast Asia. Increased temperatures and precipitation over the western Pacific Ocean was found to be associated with a Pacific-Japan like-pattern, which can affect East Asia’s climate

The World's Rediscovered Species: Back from the Brink?

Each year, numerous species thought to have disappeared are rediscovered. Yet, do these rediscoveries represent the return of viable populations or the delayed extinction of doomed species? We document the number, distribution and conservation status of rediscovered amphibian, bird, and mammal species globally. Over the past 122 years, at least 351 species have been rediscovered, most occurring in the tropics. These species, on average, were missing for 61 years before being rediscovered (range of 3–331 years). The number of rediscoveries per year increased over time and the majority of these rediscoveries represent first documentations since their original description. Most rediscovered species have restricted ranges and small populations, and 92% of amphibians, 86% of birds, and 86% of mammals are highly threatened, independent of how long they were missing or when they were rediscovered. Under the current trends of widespread habitat loss, particularly in the tropics, most rediscovered species remain on the brink of extinction

Risk Model-Based Lung Cancer Screening and Racial and Ethnic Disparities in the US

Importance The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model–based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity.Objective To validate and recalibrate the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012) model—a well-established risk prediction model based on a predominantly White population—across races and ethnicities in the US and evaluate racial and ethnic disparities and screening performance through risk-based screening using PLCOm2012 vs the USPSTF 2021 criteria.Design, Setting, and Participants In a population-based cohort design, the Multiethnic Cohort Study enrolled participants in 1993-1996, followed up through December 31, 2018. Data analysis was conducted from April 1, 2022, to May 19. 2023. A total of 105 261 adults with a smoking history were included.Exposures The 6-year lung cancer risk was calculated through recalibrated PLCOm2012 (ie, PLCOm2012-Update) and screening eligibility based on a 6-year risk threshold greater than or equal to 1.3%, yielding similar eligibility as the USPSTF 2021 guidelines.Outcomes Predictive accuracy, screening eligibility-incidence (E-I) ratio (ie, ratio of the number of eligible to incident cases), and screening performance (sensitivity, specificity, and number needed to screen to detect 1 lung cancer).Results Of 105 261 participants (60 011 [57.0%] men; mean [SD] age, 59.8 [8.7] years), consisting of 19 258 (18.3%) African American, 27 227 (25.9%) Japanese American, 21 383 (20.3%) Latino, 8368 (7.9%) Native Hawaiian/Other Pacific Islander, and 29 025 (27.6%) White individuals, 1464 (1.4%) developed lung cancer within 6 years from enrollment. The PLCOm2012-Update showed good predictive accuracy across races and ethnicities (area under the curve, 0.72-0.82). The USPSTF 2021 criteria yielded a large disparity among African American individuals, whose E-I ratio was 53% lower vs White individuals (E-I ratio: 9.5 vs 20.3; P &lt; .001). Under the risk-based screening (PLCOm2012-Update 6-year risk ≥1.3%), the disparity between African American and White individuals was substantially reduced (E-I ratio: 15.9 vs 18.4; P &lt; .001), with minimal disparities observed in persons of other minoritized groups, including Japanese American, Latino, and Native Hawaiian/Other Pacific Islander. Risk-based screening yielded superior overall and race and ethnicity–specific performance to the USPSTF 2021 criteria, with higher overall sensitivity (67.2% vs 57.7%) and lower number needed to screen (26 vs 30) at similar specificity (76.6%).Conclusions The findings of this cohort study suggest that risk-based lung cancer screening can reduce racial and ethnic disparities and improve screening performance across races and ethnicities vs the USPSTF 2021 criteria