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7 YLL within the study period, 17.28% (95% empirical CI 9.42-25.14%) of YLL and 17.27% (12.70-21.34%) of mortality were attributable to non-optimum temperature. More YLL was caused by cold (10.14%, 3.94-16.36%) than by heat (7.14%, 0.47-13.88%). Mild cold (12.2-24.5 °C) was responsible for far more YLL (8.78%, 3.00-14.61%) than extreme cold (3.5-12.2 °C). As for cardiovascular deaths, only the fractions attributable to overall and cold temperature were significant, with mild cold contributing the largest fraction to YLL (16.31%, 6.85-25.82%) and mortality (16.08%, 9.77-21.22%). Most of the temperature-related YLL and mortality was attributable to mild but non-optimum weather, especially mild cold, while the YLL model implied a more prominent heat effect on premature death. buy Tanshinone C Our findings can supply additional evidence from multiperspectives for health planners to define priorities and make targeted policies for mitigating the burden of adverse temperatures.Leukopenia is a serious, frequent side effect associated with azathioprine use. Currently, we use thiopurine methyltransferase (TPMT) testing to predict leukopenia in patients taking azathioprine. We hypothesized that a risk score incorporating additional clinical and genetic variables would improve the prediction of azathioprine-associated leukopenia. In the discovery phase, we developed four risk score models (1) age, sex, and TPMT metabolizer status; (2) model 1 plus additional clinical variables; (3) sixty candidate single nucleotide polymorphisms; and (4) model 2 plus model 3. The area under the receiver-operating-characteristic curve (AUC) of the risk scores was 0.59 (95% CI 0.54-0.64), 0.75 (0.71-0.80), 0.66 (0.61-0.71), and 0.78 (0.74-0.82) for models 1, 2, 3, and 4, respectively. link2 During the replication phase, models 2 and 4 (AUC = 0.64, 95% CI 0.59-0.70 and AUC = 0.63, 95% CI 0.58-0.69, respectively) were significant in an independent group. Compared with TPMT testing alone, additional genetic and clinical variables improve the prediction of azathioprine-associated leukopenia.The coupled model AVIM-RIEMS2.0 is employed to examine the effects of climate change on the terrestrial ecosystem over East Asia during three decades since the 1980s. The vegetation parameters present significantly different responses to climate change in subregions, since the effects of climate change trigger seasonal signals on land surface processes at the regional scale. In the 1980s, the increasing temperature and rainfall lead to a decrease in biomass and leaf area index (LAI) in winter, but a slight increase in net primary productivity (NPP) over China. However, summertime precipitation shows interval changes of cyclic increase-decrease pattern over eastern China, and the similar pattern also occurs for the variations in biomass and LAI. In the 1990s, the temperature and precipitation over the most regions in East Asia demonstrate the opposite changes compared to the 1980s, which results in converse variations in LAI and vegetation carbon flux. In the 2000s, biomass and LAI in the mid-lower reaches of Yangtze River basin and southeast coastal regions exhibit the same changes as precipitation in winter, and NPP shows a similar response to temperature. The biomass and LAI show consistent responses to regional climate change in summer, while different responses are seen for NPP. In general, climate change had a great impact on the vegetation in the 1990s, which produced the remarkable influences on LAI and biomass in winter and the significant impacts on NPP in summer. Over the regions affected significantly by East Asian monsoon, e.g. South China, the terrestrial ecosystem displays a roughly consistent response to regional climate change.Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms, which showed that long-term circadian misalignment induced significant early mortality. Non-biased RNA sequencing analysis using liver and kidney showed marked activation of gene regulatory pathways associated with the immune system and immune disease in both organs. In accordance, we observed enhanced steatohepatitis with infiltration of inflammatory cells. The investigation of senescence-associated immune cell subsets from the spleens and mesenteric lymph nodes revealed an increase in PD-1+CD44high CD4 T cells as well as CD95+GL7+ germinal center B cells, indicating that the long-term circadian misalignment exacerbates immune senescence and consequent chronic inflammation. Our results underscore immune homeostasis as a pivotal interventional target against clock-related disorders.BACKGROUND While institution-sponsored wellness programs may be effective, little is known about their availability and utilization in pediatric subspecialists, and about programs physicians wish were available. METHODS A survey of perceptions about, and availability and utilization of institutional wellness activities, was distributed electronically to pediatric subspecialists nationally. Bivariate analyses were performed using χ2 tests or independent t tests. Multivariable logistic regression models for categories of institution-sponsored programming as a function of potential predictors of program utilization were performed. Qualitative content analysis was performed for free-text survey answers. RESULTS Approximately 60% of respondents participated in institution-sponsored wellness opportunities. Debriefs, Schwartz Center Rounds, mental health services, and team building events were the most available institution-sponsored wellness activities, whereas debriefs, team building, Schwartz Center Rounds, and pet therapy were most frequently utilized. Respondents desired greater social/emotional support, improved leadership, enhanced organizational support, and modifications to the physical work environment, with no significant differences across subspecialties for "wish list" items. CONCLUSIONS Physician wellness requires more than a "one-size-fits-all" initiative. Our data highlight the importance of encouraging and normalizing self-care practices, and of listening to what physicians articulate about their needs. Pre-implementation needs assessment allows a "bottom-up" approach where physician voices can be heard.Portugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR- and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Klotho, an antiaging protein, has been shown to play a protective role in renal tubular epithelial-mesenchymal transition (EMT) during the development of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) participate in the progression of EMT in many diseases. However, the effect of Klotho on lncRNAs during the development of DKD is still unknown. In this study, we found that Klotho overexpression in high-fat diet (HFD)- and streptozotocin (STZ)-induced DKD mice significantly inhibited the expression of lncRNA nuclear-enriched abundant transcript 1 (Neat1). We demonstrated that NEAT1 was significantly upregulated in both bovine serum albumin (BSA)-stimulated HK2 cells and mice with HFD- and STZ-induced diabetes. In addition, we observed that Klotho displays colocalization with NEAT1. Furthermore, overexpression of Klotho can inhibit the high expression of NEAT1 in BSA-stimulated HK2 cells, while silencing Klotho can further upregulate the expression of NEAT1. link3 Silencing NEAT1 in HK2 cells resulted in inhibition of the EMT-related markers alpha smooth muscle actin (α-SMA) and vimentin (VIM) and the renal fibrosis-related markers transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF). The effect of NEAT1 on DKD was partly mediated by regulation of the ERK1/2 signaling pathway. Finally, we found that silencing NEAT1 can reverse the activation of EMT and fibrosis caused by Klotho silencing in a manner dependent on the ERK1/2 signaling pathway. These findings reveal a new regulatory pathway by which Klotho regulates ERK1/2 signaling via NEAT1 to protect against EMT and renal fibrosis, suggesting that NEAT1 is a potential therapeutic target for DKD.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Spintronic devices using antiferromagnets (AFMs) are promising candidates for future applications. Recently, many interesting physical properties have been reported with AFM-based devices. Here we report a butterfly-shaped magnetoresistance (MR) in a micrometer-sized triangular-lattice antiferromagnet Ag2CrO2. The material consists of two-dimensional triangular-lattice CrO2 layers with antiferromagnetically coupled S = 3/2 spins and Ag2 layers with high electrical conductivity. The butterfly-shaped MR appears only when the magnetic field is applied perpendicularly to the CrO2 plane with the maximum MR ratio (≈15%) at the magnetic ordering temperature. These features are distinct from those observed in conventional magnetic materials. We propose a theoretical model where fluctuations of partially disordered spins with the Ising anisotropy play an essential role in the butterfly-shaped MR in Ag2CrO2.OBJECTIVE To study the efficacy of intranasal fentanyl as an adjunct for pain management during screening for retinopathy of prematurity (ROP) in preterm infants. STUDY DESIGN In this single center, double blinded, randomized controlled trial, preterm neonates between 30 and 34 weeks postmenstrual age received either intranasal fentanyl (2 mcg/kg) or intranasal normal saline through a mucosal atomization device 5 min prior to the first ROP-screening examination. Both the groups received standard pain relief strategies (oral sucrose, 0.5% proparacaine eye drops and physical containment). The primary outcome was premature infant pain profile-revised (PIPP-R) score during the screening. RESULTS A total of 111 infants were enrolled. PIPP-R score during the retinal examination was significantly lower in the fentanyl group (8.3 versus 11.5, mean difference 3.2 (2.46-4.06), P less then 0.001). There was no significant difference in the incidence of adverse effects. CONCLUSION Intranasal fentanyl significantly reduced the pain associated with retinal examination without increasing the risk of respiratory depression.
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