Referral Patterns Between Allopathic Physicians and Complementary and Alternative Medicine Practitioners: A Followup Study

Introduction: • Despite the high prevalence of Complementary and Alternative Medicine (CAM) usage, several recent surveys suggest that the vast majority of patient visits to CAM practitioners are self-referred and that communication between conventional and CAM practitioners is limited. • There is a need for a better understandingof factors influencing referral patterns across these two groups of practitioners. • Network analysis provides a useful tool to quantify relationships between members of an interrelated social network. • The goal of this follow up study was to quantify the cross-class referral patterns between conventional and CAM classes of practitioners in Chittenden County Vermont as well as gather additional information on the basis of referrals for future studies. • This study was a preliminary examination of possible reasons for the referral patterns.https://scholarworks.uvm.edu/comphp_gallery/1039/thumbnail.jp

A Review of Events That Expose Children to Elemental Mercury in the United States

Concern for children exposed to elemental mercury prompted the Agency for Toxic Substances and Disease Registry and the Centers for Disease Control and Prevention to review the sources of elemental mercury exposures in children, describe the location and proportion of children affected, and make recommendations on how to prevent these exposures. In this review, we excluded mercury exposures from coal-burning facilities, dental amalgams, fish consumption, medical waste incinerators, or thimerosal-containing vaccines. We reviewed federal, state, and regional programs with data on mercury releases along with published reports of children exposed to elemental mercury in the United States. We selected all mercury-related events that were documented to expose (or potentially expose) children. Primary exposure locations were at home, at school, and at others such as industrial property not adequately remediated or medical facilities. Exposure to small spills from broken thermometers was the most common scenario; however, reports of such exposures are declining. The information reviewed suggests that most releases do not lead to demonstrable harm if the exposure period is short and the mercury is properly cleaned up. Primary prevention should include health education and policy initiatives

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer

A challenge in quantitative biology is to predict output patterns of gene expression from knowledge of input transcription factor patterns and from the arrangement of binding sites for these transcription factors on regulatory DNA. We tested whether widespread thermodynamic models could be used to infer parameters describing simple regulatory architectures that inform parameter-free predictions of more complex enhancers in the context of transcriptional repression by Runt in the early fruit fly embryo. By modulating the number and placement of Runt binding sites within an enhancer, and quantifying the resulting transcriptional activity using live imaging, we discovered that thermodynamic models call for higher-order cooperativity between multiple molecular players. This higher-order cooperativity capture the combinatorial complexity underlying eukaryotic transcriptional regulation and cannot be determined from simpler regulatory architectures, highlighting the challenges in reaching a predictive understanding of transcriptional regulation in eukaryotes and calling for approaches that quantitatively dissect their molecular nature.Data files are in MATLAB .mat file structures. Funding provided by: Burroughs Wellcome FundCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000861Award Number: Career Award at the Scientific InterfaceFunding provided by: National Institutes of HealthCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000002Award Number: P20 GM0103423Funding provided by: National Institutes of HealthCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000002Award Number: Director's New Innovator Award DP2 OD024541-01Funding provided by: National Science FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000001Award Number: CAREER Award 1652236Funding provided by: National Science FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000001Award Number: CAREER Award 1349779Funding provided by: Alfred P. Sloan FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000879Award Number: Sloan Research FellowshipFunding provided by: Searle Scholars ProgramCrossref Funder Registry ID: http://dx.doi.org/10.13039/100014185Award Number: Funding provided by: Shurl and Kay Curci FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100010319Award Number: Funding provided by: Hellman FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100010336Award Number: Funding provided by: Korea Foundation for Advanced StudiesCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100007633Award Number:Data were collected using fluorescent confocal microscopy as described in the Methods and Materials section of the main text, and processed using the image processing techniques described therein. The file 'compiledData.mat' represents the pre-and post-processed transcription data using the fitting schemes described in the main text. Data for the concentration of input transcription factors, Bicoid and Runt, are stored in 'Bicoid.mat' and 'Runt.mat' respectively

FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue

Objective: Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates metabolic homeostasis. Previous work has suggested that impairment of FGF21 signaling in adipose tissue may occur through downregulation of the obligate FGF21 co-receptor, β-klotho, which leads to “FGF21 resistance” during the onset of diet-induced obesity. Here, we sought to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance and whether other mechanisms also contribute to FGF21 resistance in vivo. Methods: We generated adipose-specific β-klotho transgenic mice to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance in vivo. Results: β-klotho protein levels are markedly decreased in white adipose tissue, but not liver or brown adipose tissue, during diet-induced obesity. Maintenance of β-klotho protein expression in adipose tissue does not alleviate impaired FGF21 signaling in white adipose or increase FGF21 sensitivity in vivo. Conclusions: In white adipose tissue, downregulation of β-klotho expression is not the major mechanism contributing to impaired FGF21 signaling in white adipose tissue. Keywords: FGF21, Resistance, Betaklotho, Obesity, Adipos

The Price of Gasoline and the Demand for Fuel Economy: Evidence from Monthly New Vehicles Sales Data

This paper uses a unique data set of monthly new vehicle sales by detailed model from 1978-2007, and implements a new identification strategy to estimate the effect of the price of gasoline on consumer demand for fuel economy. We control for unobserved vehicle and consumer characteristics by using within model-year changes in the price of gasoline and vehicle sales. We find a significant demand response, as nearly half of the decline in market share of U.S. manufacturers from 2002-2007 was due to the increase in the price of gasoline. On the other hand, an increase in the gasoline tax would only modestly affect average fuel economy

The Prometastatic Ribosomal S6 Kinase 2-cAMP Response Element-binding Protein (RSK2-CREB) Signaling Pathway Up-regulates the Actin-binding Protein Fascin-1 to Promote Tumor Metastasis

Metastasis is the leading cause of death in patients with breast, lung, and head and neck cancers. However, the molecular mechanisms underlying metastases in these cancers remain unclear. We found that the p90 ribosomal S6 kinase 2 (RSK2)-cAMP response element-binding protein (CREB) pathway is commonly activated in diverse metastatic human cancer cells, leading to up-regulation of a CREB transcription target Fascin-1. We also observed that the protein expression patterns of RSK2 and Fascin-1 correlate in primary human tumor tissue samples from head and neck squamous cell carcinoma patients. Moreover, knockdown of RSK2 disrupts filopodia formation and bundling in highly invasive cancer cells, leading to attenuated cancer cell invasion in vitro and tumor metastasis in vivo, whereas expression of Fascin-1 significantly rescues these phenotypes. Furthermore, targeting RSK2 with the small molecule RSK inhibitor FMK-MEA effectively attenuated the invasive and metastatic potential of cancer cells in vitro and in vivo, respectively. Taken together, our findings for the first time link RSK2-CREB signaling to filopodia formation and bundling through the up-regulation of Fascin-1, providing a proinvasive and prometastatic advantage to human cancers. Therefore, protein effectors of the RSK2-CREB-Fascin-1 pathway represent promising biomarkers and therapeutic targets in the clinical prognosis and treatment of metastatic human cancers