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"Lewis, Nikki"
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Feasibility of paying people who use drugs cash to distribute naloxone within their networks
Introduction
Immediate access to naloxone is needed to prevent fatal opioid-related overdoses in the presence of fentanyl analogs saturating the opioid supply. Peer models engage impacted populations who are not accessing naloxone through standard venues, yet compensating peers who utilize syringe service programs with cash stipends to distribute naloxone within networks of people who use drugs is not well described.
Methods
As part of the HEALing Communities Study, syringe service program-based interventions were developed in Holyoke and Gloucester, MA, which paid people who use drugs (“peers”) cash to distribute naloxone. Early program outcomes were evaluated for the time each program was funded within the HCS study period.
Results
During 22 study-months of observation, peers in two communities distributed 1104 naloxone kits. The total cost of peer compensation for program delivery was $10,510. The rate of peer-distributed naloxone per 100 K population reached 109 kits/mo and 222 kits/mo in the two communities. Participating peers addressed gaps in harm reduction outreach and distributed naloxone and other harm reduction equipment to individuals who were not syringe service program participants, expanding organizational reach. Being compensated with unrestricted cash stipends supported dignity and acknowledged peers’ work in overdose prevention.
Conclusion
The underutilization of compensated peer models is often attributed to funding and organizational barriers. These programs demonstrate that providing cash stipends to peers is feasible and expanded naloxone distribution at two existing syringe service programs. Providing cash stipends for peers who engage in secondary naloxone distribution offers promise in delivering naloxone to people not accessing syringe services.
Journal Article
Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths
Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices.
In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults.
During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year.
In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).
Journal Article
Social Cognitive Influences as Opposed to Early Age of Initiation in Predicting Daily Adolescent Tobacco Use and Cessation Failure
For decades, tobacco use among adolescents has been viewed as a significant public health issue based on health effects, dependency, and failed cessation. An assessment of the factors associated with smoking initiation among this population may be applied to education, cessation programs, and smoking policies by public health agencies and policy makers to improve prevention strategies. Guided by the social cognitive theory, the purpose of this quantitative study was to test if age of initiation, when compared to exogenous influences, was a stronger predictive factor for smoking and cessation failure. This study was a secondary analysis of a public survey dataset of 7,609 adolescents collected by the Centers for Disease Control and Prevention for the 2009 National Youth Tobacco Survey. Data were analyzed using logistic regression and stratified analysis. Adolescents within the older age of initiation groups (12-14 and 15-17+) were at higher risk for failing long-term cessation than those within the younger age group (9-11). For daily smoking, early age of initiation was predictive among the younger age groups (9-11 and 12-14) whereas exposure to parental acceptance, parental influence, and peer influence was predictive for the older age group (15-17+). Self-efficacy was found to be significant in predicting short- and long-term cessation failure among boys and girls. Moreover, self-efficacy was found to have an intervening effect that hindered successful long-term smoking cessation among those adolescents exposed to peer influence, tobacco in movies, and tobacco on the Internet. The results of this study may aid in educating individuals, communities, public health agencies, and policy makers on the impact that social influences continue to have on tobacco initiation, daily smoking, and cessation efforts in American adolescents.
Dissertation
United set to buy Sunstrand in $4B deal
Sunstrand has a market capitalization of approximately $3.2- billion, and while exact financial details could not be established, one person close to United said it would be paying close to $4- billion. Sunstrand would fit well with United's Pratt & Whitney business unit, which makes aircraft jet engines and spare parts.
Newspaper Article
United set to buy Sunstrand in $4B deal
United Technologies, the industrial group, is today expected to announce the acquisition of Sunstrand, the Illinois-based aerospace components manufacturer, in a deal likely to be valued at $4- billion. Sunstrand would fit well with United's Pratt & Whitney business unit, which makes aircraft jet engines and spare parts.
Newspaper Article
Detection of trace concentrations of S-nitrosothiols by means of a capacitive sensor
Small molecule S-nitrosothiols are a class of endogenous chemicals in the body, which have been implicated in a variety of biological functions. However, the labile nature of NO and the limits of current detection assays have made studying these molecules difficult. Here we present a method for detecting trace concentrations of S-nitrosothiols in biological fluids. Capacitive sensors when coupled to a semiconducting material represent a method for detecting trace quantities of a chemical in complex solutions. We have taken advantage of the semiconducting and chemical properties of polydopamine to construct a capacitive sensor and associated method of use, which specifically senses S-nitrosothiols in complex biological solutions.
Journal Article
ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance
Cyclic dinucleotide (CDN) agonists of the STimulator of InterferoN Genes (STING) pathway have shown immune activation and tumor clearance in pre-clinical models. However, CDNs administered intratumorally also promote STING activation leading to direct cytotoxicity of many cell types in the tumor microenvironment (TME), systemic inflammation due to rapid tumor extravasation of the CDN, and immune ablation in the TME. These result in a failure to establish immunological memory. ExoSTING, an engineered extracellular vesicle (EV) exogenously loaded with CDN, enhances the potency of CDN and preferentially activates antigen presenting cells in the TME. Following intratumoral injection, exoSTING was retained within the tumor, enhanced local Th1 responses and recruitment of CD8+ T cells, and generated systemic anti-tumor immunity to the tumor. ExoSTING at therapeutically active doses did not induce systemic inflammatory cytokines, resulting in an enhanced therapeutic window. ExoSTING is a novel, differentiated therapeutic candidate that leverages the natural biology of EVs to enhance the activity of CDNs.Su Chul Jang et al. develop exoSTING, consisting of an engineered extracellular vesicle loaded with a potent cyclic dinucleotide (CDN) agonist of the STING pathway. They find that exoSTING shows more than 100-fold increased potency in in vivo tumor models and has increased tumor retention and lower levels of systemic inflammatory cytokine production as compared to free CDN.
Journal Article
Key features of the innate immune response is mediated by the immunoproteasome in microglia
Microglia are the resident immune cells of the central nervous system (CNS). We and others have shown that the inflammatory response of microglia is partially regulated by the immunoproteasome, an inducible form of the proteasome responsible for the generation of major histocompatibility complex (MHC) class I epitopes. While the role of the proteasome in the adaptive immune system is well established, emerging evidence suggests the immunoproteasome may have discrete functions in the innate immune response. Here, we show that inhibiting the immunoproteasome reduces the IFNγ-dependent induction of complement activator C1q, suppresses phagocytosis, and alters the cytokine expression profile in a microglial cell line (BV2) and microglia derived from human inducible pluripotent stem cells. Moreover, we show that the immunoproteasome regulates the degradation of IκBα, a modulator of NF-κB signaling. Finally, we demonstrate that NADH prevents induction of the immunoproteasome, representing a potential pathway to suppress immunoproteasome-dependent immune responses.
Journal Article