Medicare Hospital Readmissions Reduction Program

Outlines national health reform provisions to reduce readmissions by publishing readmission data, lowering Medicare payments to hospitals with high readmission rates, and pairing such hospitals with patient safety organizations. Considers implications

Cten promotes Epithelial–Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src

Cten is an oncogene promoting EMT in many signaling pathways, namely through Snail. We investigated whether Cten function could be mediated through Src. Cten levels were modulated by forced expression in HCT116 and gene knockdown in SW620 CRC (colorectal cancer) cell lines. In all cell lines, Cten was a positive regulator of Src expression. The functional importance of Src was tested by simultaneous Cten overexpression and Src knockdown. This resulted in abrogation of Cten motility-inducing activity and reduction of colony formation ability together with failure to induce Cten targets. In SW620ΔCten reduced Src expression increased following restoration of Cten, also leading to increased cell motility and colony formation, which were lost if Src was concomitantly knocked down. By qRT-PCR we showed modulation of Cten had no effect on Src mRNA. However, a CHX pulse chase assay demonstrated stabilization of Src protein by Cten. Finally, expression of Cten and Src was tested in a series of 84 primary CRCs and there was a significant correlation between them (P = 0.001). We conclude that Src is a novel and functionally important target of the Cten signaling pathway and that Cten protein causes post-transcriptional stabilization of Src in promoting EMT and possibly metastasis in CRC

Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice

Background Sirtuins are important regulators of glucose and fat metabolism, and sirtuin activation has been proposed as a therapeutic target for insulin resistance and diabetes. We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Resveratrol is a widely recognized activator of Sirt; however, the biologically-effective high concentrations used in cell and animal studies are generally impractical or difficult to achieve in humans. Accordingly, we sought to determine whether leucine would exhibit synergy with low levels of resveratrol on sirtuin-dependent outcomes in adipocytes and in diet-induced obese (DIO) mice. Methods 3T3-L1 mouse adipocytes were treated with Leucine (0.5 mM), β-hydroxy-β-methyl butyrate (HMB) (5 μM) or Resveratrol (200 nM) alone or in combination. In addition, diet-induced obese mice were treated for 6-weeks with low (2 g/kg diet) or high (10 g/kg diet) dose HMB, Leucine (24 g/kg diet; 200% of normal level) or low (12.5 mg/kg diet) or high (225 mg/kg diet) dose resveratrol, alone or as combination with leucine-resveratrol or HMB-resveratrol. Results Fatty acid oxidation, AMPK, Sirt1 and Sirt3 activity in 3T3-L1 adipocytes and in muscle cells, were significantly increased by the combinations compared to the individual treatments. Similarly, 6-week feeding of low-dose resveratrol combined with either leucine or its metabolite HMB to DIO mice increased adipose Sirt1 activity, muscle glucose and palmitate uptake (measured via PET/CT), insulin sensitivity (HOMAIR), improved inflammatory stress biomarkers (CRP, IL-6, MCP-1, adiponectin) and reduced adiposity comparable to the effects of high dose resveratrol, while low-dose resveratrol exerted no independent effect. Conclusion These data demonstrate that either leucine or its metabolite HMB may be combined with a low concentration of resveratrol to exert synergistic effects on Sirt1-dependent outcomes; this may result in more practical dosing of resveratrol in the management of obesity, insulin-resistance and diabetes

25-hydroxyvitamin D and health service utilization for asthma in early childhood

Introduction Asthma is the most common chronic illness of childhood and a common reason for hospital admission. Studies suggest that low vitamin D levels may be associated with health service utilization (HSU) for childhood asthma. Objectives and Approach The primary objective was to determine if vitamin D serum levels in early childhood were associated with HSU for asthma including: a) total HSU, b) hospital admissions, c) emergency department visits and d) outpatient sick visits. Secondary objectives were to determine whether vitamin D supplementation in pregnancy or childhood were associated with HSU for asthma. Prospective cohort study of children participating in the TARGet Kids! practice based research network. HSU was determined by linking each child's provincial health insurance number to health administrative databases. Multivariable quasi Poisson and logistic regression were used to evaluate the associations. Results 2926 healthy children ages 0-6 years had 25-hydroxyvitamin D data available and were included in the primary analysis. Mean (IQR) 25-hydroxyvitmain D level was 84 nmol/L (65-98 nmol/L), 218 and 1267 children had 25-hydroxyvitamin D levels <50 nmol/L and <75 nmol/L, respectively. In the adjusted models, there were no associations between 25-hydroxyvitamin D (continuously or dichotomized at 50 and 75 nmol/L), vitamin D supplementation in pregnancy or childhood and HSU for asthma. Conclusion/Implications Higher vitamin D blood values do not appear to be associated with HSU for asthma in this population of healthy urban children

Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects

PublishedResearch Support, Non-U.S. Gov'tBACKGROUND: Environmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established. OBJECTIVES: We assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent). METHODS: Growth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17 alpha-ethinyl-estradiol (EE2)], and to EE2 alone. RESULTS: In addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE2 were modified when it was present in a complex mixture (i.e., spiked into effluent), suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes. CONCLUSION: These data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures.This work was funded by the Environment Agency to C.R.T. (project no. SC040078). T.N. was supported by a Fundação para a Ciência ea Tecnologia (FCT) fellowship (BPD/18192/04)

Comparing two asthma diagnoses using a prospective cohort of young children

Introduction Asthma is the most common chronic illness of childhood and places a large burden on the health care system. Asthma prevalence is commonly measured in national surveys by questionnaire. In Ontario, the Ontario Asthma Surveillance Information System (OASIS) developed a validated health claims diagnosis algorithm using health administrative data. Objectives and Approach The primary objective of this study was to measure the agreement between the health claims diagnosis algorithm (OASIS diagnosis algorithm) and questionnaire diagnosis (TARGet Kids! diagnosis) of asthma in children younger than 6 years of age. Secondary objectives were to identify concordant and discordant pairs, and to identify factors associated with disagreement. A comparison study including 3368 children participating in the TARGet Kids! practice based research network between 2008 and 2013 in Toronto, Canada. OASIS diagnosis algorithm and TARGet Kids! diagnosis asthma cases were compared using kappa statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results Prevalence of asthma was estimated to be 15% by the OASIS diagnosis algorithm and 7% by TARGet Kids! diagnosis. The Kappa statistic was 0.47 (95% CI: 0.42 – 0.51), sensitivity 82\%, specificity 90%, PPV 38% and NPV 98% for OASIS diagnosis algorithm using TARGet Kids! diagnosis as the criterion standard. There were 3011 concordant pairs (2820 true negatives and 191 true positives) and 357 discordant pairs (315 false positives and 42 false negatives). Statistically significant factors associated with false positives included: male sex, higher zBMI and history of allergy. No statistically significant factors associated with false negatives were identified. Conclusion/Implications OASIS diagnosis algorithm had high sensitivity, specificity, and NPV but low PPV relative to TARGet Kids! diagnosis of asthma. Although, the OASIS diagnosis may identify more asthma cases in young children, its diagnostic properties are similar in older children and it may be a useful tool for longitudinal asthma surveillance

Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Erratum in: Nat Commun. 2023 Mar 20;14(1):1539. doi: 10.1038/s41467-023-37302-5.Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori fromEurope and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks bymigration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.This work was supported by Sequencing Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (221S0002, 18KK0266, 19H03473, 21H00346 and 22H02871) to Y.Y. F.F.V. is financed by FCT through Assistant Researcher grant CEECIND/03023/2017 and a project grant PTDC/BTM-TEC/3238/ 2020. I.K. studentship was funded by the National Strategic Reference Framework Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020, project No. MIS5002486) and sequencing of strains was supported by the InfeNeutra Project (NSRF 2007-2013, project no. MIS450598) of the Ministry of Culture and Edu- cation, Greece. K.T. and the sequencing of KI isolates was supported by Erik Philip-Sörensen Foundation grant G2016-08, and Swedish Society for Medical research (SSMF). All primary bioinformatics and parts of the comparative genomics were performed on resources provided by Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under projects snic2018-8-24 and uppstore2017270. Work by S.S. was supported by the German Research Foundation (DFG, project number 158 989 968–SFB 900/A1) and by the Bavarian Ministry of Sci- ence and the Arts in the framework of the Bavarian Research Network “New Strategies Against Multi-Resistant Pathogens by Means of Digital Networking—bayresq.net”. D.F. was supported by Shanghai Municipal Science and Technology Major Project No. 2019SHZDZX02.info:eu-repo/semantics/publishedVersio

Dairy attentuates oxidative and inflammatory stress in metabolic syndrome123

Background: Oxidative and inflammatory stress are elevated in obesity and are further augmented in metabolic syndrome. We showed previously that dairy components suppress the adipocyte- and macrophage-mediated generation of reactive oxygen species and inflammatory cytokines and systemic oxidative and inflammatory biomarkers in obesity

Benchmarking spike-based visual recognition: a dataset and evaluation

Today, increasing attention is being paid to research into spike-based neural computation both to gain a better understanding of the brain and to explore biologically-inspired computation. Within this field, the primate visual pathway and its hierarchical organisation have been extensively studied. Spiking Neural Networks (SNNs), inspired by the understanding of observed biological structure and function, have been successfully applied to visual recognition and classification tasks. In addition, implementations on neuromorphic hardware have enabled large-scale networks to run in (or even faster than) real time, making spike-based neural vision processing accessible on mobile robots. Neuromorphic sensors such as silicon retinas are able to feed such mobile systems with real-time visual stimuli. A new set of vision benchmarks for spike-based neural processing are now needed to measure progress quantitatively within this rapidly advancing field. We propose that a large dataset of spike-based visual stimuli is needed to provide meaningful comparisons between different systems, and a corresponding evaluation methodology is also required to measure the performance of SNN models and their hardware implementations. In this paper we first propose an initial NE (Neuromorphic Engineering) dataset based on standard computer vision benchmarks and that uses digits from the MNIST database. This dataset is compatible with the state of current research on spike-based image recognition. The corresponding spike trains are produced using a range of techniques: rate-based Poisson spike generation, rank order encoding, and recorded output from a silicon retina with both flashing and oscillating input stimuli. In addition, a complementary evaluation methodology is presented to assess both model-level and hardware-level performance. Finally, we demonstrate the use of the dataset and the evaluation methodology using two SNN models to validate the performance of the models and their hardware implementations. With this dataset we hope to (1) promote meaningful comparison between algorithms in the field of neural computation, (2) allow comparison with conventional image recognition methods, (3) provide an assessment of the state of the art in spike-based visual recognition, and (4) help researchers identify future directions and advance the field

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy