2,540 research outputs found

    Risk of developing gallbladder cancer in patients with gallbladder polyps detected on transabdominal ultrasound: a systematic review and meta-analysis

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    Objective: To estimate the risk of malignancy in gallbladder polyps of incremental sizes detected during transabdominal ultrasound (TAUS). Methods: We searched databases including MEDLINE, Embase, and Cochrane Library for eligible studies recording the polyp size from which gallbladder malignancy developed, confirmed following cholecystectomy, or by subsequent follow-up. Primary outcome was the risk of gallbladder cancer in patients with polyps. Secondary outcome was the effect of polyp size as a prognostic factor for cancer. Risk of bias was assessed using the Quality in Prognostic Factor Studies (QUIPS) tool. Bayesian meta-analysis estimated the median cancer risk according to polyp size. This study is registered with PROSPERO (CRD42020223629). Results: 82 studies published since 1990 reported primary data for 67,837 patients. 67,774 gallbladder polyps and 889 cancers were reported. The cumulative median cancer risk of a polyp measuring 10 mm or less was 0.60% (99% credible range 0.30–1.16%). Substantial heterogeneity existed between studies (I2 = 99.95%, 95% credible interval 99.86–99.98%). Risk of bias was generally high and overall confidence in evidence was low. 13 studies (15.6%) were graded with very low certainty, 56 studies (68.3%) with low certainty, and 13 studies (15.6%) with moderate certainty. In studies considered moderate quality, TAUS monitoring detected 4.6 cancers per 10,000 patients with polyps less than 10 mm. Conclusion: Malignant risk in gallbladder polyps is low, particularly in polyps less than 10 mm, however the data are heterogenous and generally low quality. International guidelines, which have not previously modelled size data, should be informed by these findings

    Styryllactones from Goniothalamus tamirensis

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    The phytochemical investigation of the twig and leaf extracts of Goniothalamus tamirensis led to the isolation and identification of 15 compounds including three rare previously undescribed styryllactones, goniotamirenones A-C, together with 12 known compounds. (Z)-6-Styryl-5,6-dihydro-2-pyranone and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one are reported here for the first time as previously undescribed natural products. Their structures were elucidated by spectroscopic methods. Goniotamirenone A was synthesized via a [2 + 2] cycloaddition reaction of 6-styrrylpyran-2-one in quantitative yield. The absolute configurations of goniotamirenones B and C were identified from experimental and calculated ECD data, while the absolute configurations of (−)-5-acetoxygoniothalamin, (−)-isoaltholactone, parvistone E, and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one were identified by single-crystal X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of the other related compounds were determined from comparisons of their ECD spectra with relevant compounds reported in the literature. (−)-5-Acetoxygoniothalamin exhibited potent cytotoxicity against the colon cancer cell line (HCT116) with an IC50 value of 8.6 μM which was better than the standard control (doxorubicin, IC50 = 9.7 μM), while (Z)-6-styryl-5,6-dihydro-2-pyranone was less active with an IC50 value of 22.1 μM

    The International DORIS Service (IDS) - Recent Developments in Preparation for ITRF2013

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    The International DORIS Service (IDS) was created in 2003 under the umbrella of the International Association of Geodesy (IAG) to foster scientific research related to the French DORIS tracking system and to deliver scientific products, mostly related to the International Earth rotation and Reference systems Service (IERS). We first present some general background related to the DORIS system (current and planned satellites, current tracking network and expected evolution) and to the general IDS organization (from Data Centers, Analysis Centers and Combination Center). Then, we discuss some of the steps recently taken to prepare the IDS submission to ITRF2013 (combined weekly time series based on individual solutions from several Analysis Centers). In particular, recent results obtained from the Analysis Centers and the Combination Center show that improvements can still be made when updating physical models of some DORIS satellites, such as Envisat, Cryosat-2 or Jason-2. The DORIS contribution to ITRF2013 should also benefit from the larger number of ground observations collected by the last generation of DGXX receivers (first instrument being onboard Jason-2 satellite). In particular for polar motion, sub-millarcsecond accuracy seems now to be achievable. Weekly station positioning internal consistency also seems to be improved with a larger DORIS constellation

    Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

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    BackgroundRecurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population.Methods/designIn this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care.DiscussionIf this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings.Trial registrationClinicalTrials.gov Identifier NCT01763203

    Climate vulnerability assessment for Pacific salmon and steelhead in the California Current Large Marine Ecosystem.

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    Major ecological realignments are already occurring in response to climate change. To be successful, conservation strategies now need to account for geographical patterns in traits sensitive to climate change, as well as climate threats to species-level diversity. As part of an effort to provide such information, we conducted a climate vulnerability assessment that included all anadromous Pacific salmon and steelhead (Oncorhynchus spp.) population units listed under the U.S. Endangered Species Act. Using an expert-based scoring system, we ranked 20 attributes for the 28 listed units and 5 additional units. Attributes captured biological sensitivity, or the strength of linkages between each listing unit and the present climate; climate exposure, or the magnitude of projected change in local environmental conditions; and adaptive capacity, or the ability to modify phenotypes to cope with new climatic conditions. Each listing unit was then assigned one of four vulnerability categories. Units ranked most vulnerable overall were Chinook (O. tshawytscha) in the California Central Valley, coho (O. kisutch) in California and southern Oregon, sockeye (O. nerka) in the Snake River Basin, and spring-run Chinook in the interior Columbia and Willamette River Basins. We identified units with similar vulnerability profiles using a hierarchical cluster analysis. Life history characteristics, especially freshwater and estuary residence times, interplayed with gradations in exposure from south to north and from coastal to interior regions to generate landscape-level patterns within each species. Nearly all listing units faced high exposures to projected increases in stream temperature, sea surface temperature, and ocean acidification, but other aspects of exposure peaked in particular regions. Anthropogenic factors, especially migration barriers, habitat degradation, and hatchery influence, have reduced the adaptive capacity of most steelhead and salmon populations. Enhancing adaptive capacity is essential to mitigate for the increasing threat of climate change. Collectively, these results provide a framework to support recovery planning that considers climate impacts on the majority of West Coast anadromous salmonids

    BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo

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    There has been an increasing recognition that mitochondrial perturbations play a central role in human heart failure. Discovery of mitochondrial networks, whose function is to maintain the regulation of mitochondrial biogenesis, autophagy (‘mitophagy’) and mitochondrial fusion/fission, are new potential therapeutic targets. Yet our understanding of how the molecular underpinning of these processes is just emerging. We recently identified a role of the SWI/SNF ATP-dependent chromatin remodeling complexes in the metabolic homeostasis of the adult cardiomyocyte using cardiomyocyte-specific and inducible deletion of the SWI/SNF ATPases BRG1 and BRM in adult mice (Brg1/Brm double mutant mice). To build upon these observations in early alterated metabolism, the present study looks at the subsequent alterations in mitochondrial quality control mechanisms in the impaired adult cardiomyocyte. We identified that Brg1/Brm double-mutant mice exhibited an increased mitochondrial biogenesis, increases in ‘mitophagy’, and alterations in mitochondrial fission and fusion that led to small, fragmented mitochondria. Mechanistically, increases in the autophagy and mitophagy-regulated proteins Beclin1 and Bnip3 were identified, paralleling changes seen in human heart failure. Cardiac mitochondrial dynamics were perturbed including decreased mitochondria size, reduced number, and altered expression of genes regulating fusion (Mfn1, Opa1) and fission (Drp1). We also identified cardiac protein amyloid accumulation (aggregated fibrils) during disease progression along with an increase in pre-amyloid oligomers and an upregulated unfolded protein response including increased GRP78, CHOP, and IRE-1 signaling. Together, these findings described a role for BRG1 and BRM in mitochondrial quality control, by regulating mitochondrial number, mitophagy, and mitochondrial dynamics not previously recognized in the adult cardiomyocyte. As epigenetic mechanisms are critical to the pathogenesis of heart failure, these novel pathways identified indicate that SWI/SNF chromatin remodeling functions are closely linked to mitochondrial quality control mechanisms

    Nationwide emergency department visits for pediatric traumatic spinal cord injury in the United States, 2016–2020

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    IntroductionTraumatic spinal cord injury (tSCI) is a debilitating neurological condition resulting in lifelong disability for many individuals. The primary objectives of our study were to describe national trends in incident emergency department (ED) visits for tSCI among children (less than 21 years) in the United States, and to determine the proportion of visits that resulted in immediate hospitalization each year, including stratified by age and sex. Secondary objectives were to examine associations between select characteristics and hospitalization following tSCI, as well as to assess sports-related tSCIs over time, including by individual sport and geographic region.MethodsWe used the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample to identify ED visits among children between January 2016 and December 2020 for incident tSCI. Diagnosis codes were used to identify tSCI and sports-related injury etiologies. Census Bureau data were used to approximate annual rates of pediatric ED visits for tSCI per 100,000 children. Unconditional logistic regression modeling assessed whether select factors were associated with hospital admission.ResultsWe found that the annual ED visit rate for tSCI remained relatively stable between 2016 and 2020, with approximately 2,200 new all-cause pediatric ED visits for tSCI annually. Roughly 70% of ED visits for tSCI resulted in hospitalization; most ED visits for tSCI were by older children (15–20 years) and males, who were also more often admitted to the hospital. Notable secondary findings included: (a) compared with older children (15–20 years), younger children (10–14 years) were less likely to be hospitalized immediately following an ED visit for tSCI; (b) patient sex and race were not associated with hospital admission; and (c) American tackle football was the leading cause of sports-related ED visits for tSCI among children. Our findings also suggest that the proportion of sports-related tSCI ED visits may have increased in recent years.DiscussionFuture research should further examine trends in the underlying etiologies of pediatric tSCI, while assessing the effectiveness of new and existing interventions aimed at tSCI prevention
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