The need for effective approaches to support aging and homebound adults is recognized internationally and domestically. This exploratory study sought to understand the proximal benefits of an intergenerational program in Delaware, USA that connected homebound individuals with college students. The primary goal was to describe program impacts on home-bound community residents to inform future research, program planning, and implementation.
View Article and Find Full Text PDFOpioid analgesics such as morphine and fentanyl induce mu-opioid receptor (MOR)-mediated hyperactivity in mice. Herein, we show that morphine, fentanyl, SR-17018, and oliceridine have submaximal intrinsic efficacy in the mouse striatum using S-GTPγS binding assays. While all of the agonists act as partial agonists for stimulating G protein coupling in striatum, morphine, fentanyl, and oliceridine are fully efficacious in stimulating locomotor activity; meanwhile, the noncompetitive biased agonists SR-17018 and SR-15099 produce submaximal hyperactivity.
View Article and Find Full Text PDFInt J Environ Res Public Health
December 2022
This review identifies the most promising intervention strategies for promoting the purchase and consumption of healthier items within U.S. grocery retail settings, with a particular focus on those strategies that may be most effective when implemented within SNAP-authorized retail settings.
View Article and Find Full Text PDFWe report a higher percentage of Sindbis virus-specific IgG in serum from patients attending a rheumatology clinic (18.8%) compared with healthy residents (9.6%) and patients with acute febrile illness (9.
View Article and Find Full Text PDFThe severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells.
View Article and Find Full Text PDFThe ability of a ligand to preferentially promote engagement of one signaling pathway over another downstream of GPCR activation has been referred to as signaling bias, functional selectivity, and biased agonism. The presentation of ligand bias reflects selectivity between active states of the receptor, which may result in the display of preferential engagement with one signaling pathway over another. In this study, we provide evidence that the G protein-biased mu opioid receptor (MOR) agonists SR-17018 and SR-14968 stabilize the MOR in a wash-resistant yet antagonist-reversible G protein-signaling state.
View Article and Find Full Text PDFIntroduction: Despite UN recommendations to monitor food insecurity using the Food Insecurity Experience Scale (FIES), to date there are no published reports of its validity for The Bahamas, nor have prevalence rates of moderate or severe food insecurity been reported for the remote island nation. At the same time, food security is a deep concern, with increasing incidence of natural disasters and health concerns related to diet-related disease and dietary quality plaguing the nation and its food system. This article aims to examine the validity of the FIES for use in The Bahamas, the prevalence of moderate and severe food insecurity, and the sociodemographic factors that contribute to increased food insecurity.
View Article and Find Full Text PDFThe consumption of sugar-sweetened beverages (SSBs) has been linked to obesity, diabetes, and other negative health outcomes among children. In response, many government entities have enacted healthy default beverage policies that require restaurants offering bundled kids' meals-food and drink items combined and sold as a single unit-to include only healthier drinks. Despite growing interest in these policies, little is known about their potential reach, restaurant management perceptions, and possible implementation challenges.
View Article and Find Full Text PDFThe mu opioid receptor-selective agonist, SR-17018, preferentially activates GTPγS binding over βarrestin2 recruitment in cellular assays, thereby demonstrating signaling bias. In mice, SR-17018 stimulates GTPγS binding in brainstem and produces antinociception with potencies similar to morphine. However, it produces much less respiratory suppression and mice do not develop antinociceptive tolerance in the hot plate assay upon repeated dosing.
View Article and Find Full Text PDFIt has been demonstrated that opioid agonists that preferentially act at μ-opioid receptors to activate G protein signaling over βarrestin2 recruitment produce antinociception with less respiratory suppression. However, most of the adverse effects associated with opioid therapeutics are realized after extended dosing. Therefore, we tested the onset of tolerance and dependence, and assessed for neurochemical changes associated with prolonged treatment with the biased agonist SR-17018.
View Article and Find Full Text PDFAccurate fiber tip tracking is a critical clinical problem during endovenous laser ablation (EVLA) of small perforating veins. Currently, ultrasound (US) imaging is the gold-standard modality for visualizing and for accurately placing the ablation fiber within the diseased vein. However, US imaging has limitations such as angular dependency and comet tail artifacts.
View Article and Find Full Text PDFIntroduction: The objective of this study is to compare the clinical outcomes of patients with varicose veins managed in the telemedicine clinic and traditional clinic.
Methods: Retrospective analysis of all vein procedures in the institutional Vascular Quality Initiative Varicose Vein Registry (VQI VVR) was performed from January 2015 to August 2017. Patients were divided into two groups: Telemedicine versus Traditional Clinic.
While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents.
View Article and Find Full Text PDFJ Vasc Surg Venous Lymphat Disord
November 2018
Background: Risk factors for chronic venous disease (CVD) have been widely reported in population health management. However, predisposing factors associated with patients treated for advanced stages of CVD have yet to be established. We examined the demographics and risk factors associated with advanced clinical presentation of CVD for patients referred for vein ablation.
View Article and Find Full Text PDFGPR119 drug discovery efforts in the pharmaceutical industry for the treatment of type 2 diabetes mellitus (T2DM) and obesity, were initiated based on its restricted distribution in pancreas and GI tract, and its possible role in glucose homeostasis. While a number of lead series have emerged, the pharmacological endpoints they provide have not been clear. In particular, many lead series have demonstrated loss of efficacy and significant toxic side effects.
View Article and Find Full Text PDFBiased agonism has been proposed as a means to separate desirable and adverse drug responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe structural features of a series of mu-opioid-receptor (MOR)-selective agonists that preferentially activate receptors to couple to G proteins or to recruit βarrestin proteins. By comparing relative bias for MOR-mediated signaling in each pathway, we demonstrate a strong correlation between the respiratory suppression/antinociception therapeutic window in a series of compounds spanning a wide range of signaling bias.
View Article and Find Full Text PDFContamination by and persistence of pathogenic bacteria in ready-to-eat produce have emerged as significant food safety and public health concerns. Viable produceborne pathogens cope with several stresses (e.g.
View Article and Find Full Text PDFThe reductive lithiation of phenyl thioethers, or alkyl chlorides, by either preformed aromatic radical anions or by lithium metal and an aromatic electron-transfer catalyst, is commonly used to prepare organolithiums. Revealed herein is that these two methods are fundamentally different. Reductions with radical anions occur in solution, whereas the catalytic reaction occurs on the surface of lithium, which is constantly reactivated by the catalyst, an unconventional catalyst function.
View Article and Find Full Text PDFA simple method is presented for the highly stereoselective reductions of ketones to the most thermodynamically stable alcohols. In this procedure, the ketone is treated with lithium dispersion and either FeCl2·4H2O or CuCl2·2H2O in THF at room temperature. This protocol is applied to a large number and variety of ketones and is both more convenient and efficient than those commonly reported for the diastereoselective reduction of five- and six-membered cyclic ketones.
View Article and Find Full Text PDFOne of the most widely used methods of preparation of organolithium compounds is by the reductive lithiation of alkyl phenyl thioethers or, usually less conveniently, alkyl halides with either aromatic radical-anions of lithium or lithium metal in the presence of an aromatic electron-transfer catalyst. Here we present results showing that lithium dispersion can achieve reductive lithiation in the absence of the electron-transfer agent. This procedure is more efficient, and surprisingly, the order of reactivity of substrates is reversed depending on whether the electron-transfer agent is present or absent.
View Article and Find Full Text PDFBackground: This study evaluates the relationship between body mass index (BMI) and other comorbidities on the overall morbidity and mortality of abdominal aortic aneurysm (AAA) repair.
Methods: A database of all nonemergent open and endovascular AAA repairs performed at our center from 2004 to 2008 was created. The outcomes at the predefined time intervals were then evaluated for each group of patients.