Racial and ethnic discrimination and DSM-5 substance use disorders among U.S. adults.

Objective: Racial and ethnic discrimination is a risk factor for substance use among United States adults. However, whether discrimination is associated with substance use disorders (SUDs) overall and by race and ethnicity is less understood.

Methods: We used data from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (n=35,355) and defined past-year discrimination as a summary scale (range: 0-4).

Social Network Barriers to Extended-Release Naltrexone Within Rural Appalachia: Perspectives from Justice-Involved Clients and Clinicians.

Background: Extended-release naltrexone (XR-NTX, Vivitrol) is an effective, but underutilized, evidence-based treatment for people with opioid use disorder (POUD) who are incarcerated. Networks of family, friends, and clinicians serve as social influencers of health behaviors, including XR-NTX initiation, and are especially salient in Appalachia.

Objectives: Using a triangulation of perspectives, this study examined concordance between the social network themes that emerged from qualitative interviews with clinicians and POUD social network findings.

Description of implementing a mail-based overdose education and naloxone distribution program in community supervision settings during COVID-19.

Introduction: This study uses the Exploration, Preparation, Implementation, and Sustainment (EPIS) model to retrospectively describe the mail-based overdose education and naloxone distribution (OEND) program developed in collaboration with the Kentucky Department of Corrections (DOC) for use in the HEALing Communities Study in Kentucky (HCS-KY) and details the reach of this innovative delivery model.

Methods: HCS-KY is a community-engaged cluster-randomized trial assessing the effects of implementing evidence-based practices, including OEND, on overdose death reduction across 16 communities highly impacted by the opioid epidemic in Kentucky. The study launch coincided with the COVID-19 pandemic.

Leveraging local knowledge to contextualize the opioid epidemic within HEALing Communities Study communities: A Photovoice protocol.

Since its inception 30 years ago, Photovoice has gained increasing popularity as a research method and more recently has been incorporated within randomized controlled trial (RCT) designs. Photovoice is a participatory action research method that pairs photography with focus group discussions to record community strengths and concerns, build critical consciousness, and reach policymakers. Adherence of Photovoice implementation to these original tenets of Photovoice varies.

Rapid jail-based implementation of overdose education and naloxone distribution in response to the COVID-19 pandemic.

Background: People incarcerated in jails are highly impacted by the opioid epidemic, and overdose education and naloxone distribution (OEND) is an effective strategy to reduce opioid overdose deaths. This study examines barriers and facilitators of fast-track OEND implementation within the jails in the Wave 1 Kentucky counties of the HEALing Communities Study during the COVID-19 pandemic.

Methods: Meeting minutes with jail stakeholders were qualitatively coded using the Practical, Robust Implementation and Sustainability Model (PRISM) as the coding framework.

Using Photovoice to Improve Engagement in Community Health Assessments Addressing Behavioral Health.

Behavioral health disorders are well-known to have close links with the social determinants of health, yet little is known about how impacted communities perceive these links. Qualitative participatory methods can not only provide insight into how communities conceptualize these relationships but also empower those with lived experience to contextualize their perspectives and formulate calls to action. This study used Photovoice as a participatory method to supplement the Clark County Health Department Community Health Assessment and determine priority facilitators and barriers contributing to the behavioral health of Clark County, KY, residents.

Rural and urban clinician views on COVID-19's impact on substance use treatment for individuals on community supervision in Kentucky.

Background: The COVID-19 pandemic produced system-level changes within the criminal legal system and community-based substance use disorder (SUD) treatment system with impacts on recovery efforts. This study examines rural and urban clinicians' perspectives of COVID-19 on SUD treatment delivery for people on community supervision.

Methods: Virtual qualitative interviews were conducted between April and October 2020 with 25 community supervision clinicians employed by Kentucky's Department of Corrections (DOC), who conduct assessments and facilitate community-based treatment linkages for individuals on probation or parole.

Barriers and facilitators to the use of medication for opioid use disorder within the criminal justice system: Perspectives from clinicians.

Introduction: This study examines social service clinicians' (SSCs) perspectives of factors within the criminal justice system that impact justice-involved individuals' use of medications for opioid use disorder (MOUD). Opioid use disorder (OUD) rates are high among justice-involved individuals, and overdose risk is heightened upon release from incarceration. This study is innovative, as it specifically focuses on criminal justice contexts that influence the MOUD continuum of care from the perspective of clinicians working within the criminal justice system.

Social ecological factors and medication treatment for opioid use disorder among justice-involved rural and urban persons: the eographic variation in ddiction reatment xperiences (GATE) longitudinal cohort study protocol.

Introduction: Three medications are Food and Drug Administration approved for the treatment of opioid use disorder (OUD); however, these medications are underused within prisons, which elevates the risk of relapse and overdose when persons with opioid use disorder (POUD) are released. Research is scant regarding the multilevel factors associated with POUDs' willingness to initiate medication treatment for opioid use disorder (MOUD) while in prison and their continued engagement in treatment after release. Furthermore, rural and urban populations have not been compared.

Microfluidic Squeezing Enables MHC Class I Antigen Presentation by Diverse Immune Cells to Elicit CD8 T Cell Responses with Antitumor Activity.

CD8 T cell responses are the foundation of the recent clinical success of immunotherapy in oncologic indications. Although checkpoint inhibitors have enhanced the activity of existing CD8 T cell responses, therapeutic approaches to generate Ag-specific CD8 T cell responses have had limited success. Here, we demonstrate that cytosolic delivery of Ag through microfluidic squeezing enables MHC class I presentation to CD8 T cells by diverse cell types.

The role of domestic violence in fatal mass shootings in the United States, 2014-2019.

Background: Fatal mass shootings, defined as four or more people killed by gunfire, excluding the perpetrator, account for a small percentage of firearm homicide fatalities. Research has not extensively focused on the role of domestic violence (DV) in mass shootings in the United States. This study explores the role of DV in mass shootings in the United States.

Worth the risk? Gun carrying and perceived criminal justice responses in Baltimore.

Introduction: Policing strategies to deter illegal gun carrying by high-risk people are associated with reductions in gun violence. Many factors influence decisions to use or carry a gun in public, but it is unclear whether perceptions of the criminal justice system's response influence those decisions.

Methods: We used a 2016 cross-sectional survey of criminal justice system-involved men in Baltimore City (n=195) to assess their recent frequency of gun carrying and perceptions of criminal justice system responses.

Describing a "mass shooting": the role of databases in understanding burden.

Background: The mass shooting phenomenon has gained much attention lately as this form of gun violence appears to increase in frequency. Although many organizations collect information on mass shootings (fatal and nonfatal injuries), no federal definition of this phrase exists. The purpose of this study was to highlight the different statistics that result among databases that define and track "mass shootings.

Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.

Nitric oxide contributes to protection from tuberculosis. It is generally assumed that this protection is due to direct inhibition of Mycobacterium tuberculosis growth, which prevents subsequent pathological inflammation. In contrast, we report that nitric oxide primarily protects mice by repressing an interleukin-1- and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes bacterial replication.

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection.

IL-21 is produced predominantly by activated CD4 T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (γ) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8 T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4 and CD8 T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3.

Inflammatory signaling in human tuberculosis granulomas is spatially organized.

Granulomas are the pathological hallmark of tuberculosis (TB). However, their function and mechanisms of formation remain poorly understood. To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner.

Multiple Inflammatory Cytokines Converge To Regulate CD8+ T Cell Expansion and Function during Tuberculosis.

The differentiation of effector CD8(+) T cells is a dynamically regulated process that varies during different infections and is influenced by the inflammatory milieu of the host. In this study, we define three signals regulating CD8(+) T cell responses during tuberculosis by focusing on cytokines known to affect disease outcome: IL-12, type I IFN, and IL-27. Using mixed bone marrow chimeras, we compared wild-type and cytokine receptor knockout CD8(+) T cells within the same mouse following aerosol infection with Mycobacterium tuberculosis.

A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis.

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.

Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection.

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown.

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus.

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year.

In search of a new paradigm for protective immunity to TB.

Clinical trials of vaccines against Mycobacterium tuberculosis are well under way and results are starting to come in. Some of these results are not so encouraging, as exemplified by the latest Aeras-422 and MVA85A trials. Other than empirically determining whether a vaccine reduces the number of cases of active tuberculosis, which is a daunting prospect given the chronic nature of the disease, we have no way of assessing vaccine efficacy.

Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts.

Objective: To analyse gene expression patterns and to define a specific gene expression signature in patients with the severe end of the spectrum of cryopyrin-associated periodic syndromes (CAPS). The molecular consequences of interleukin 1 inhibition were examined by comparing gene expression patterns in 16 CAPS patients before and after treatment with anakinra.

Methods: We collected peripheral blood mononuclear cells from 22 CAPS patients with active disease and from 14 healthy children.

Efferocytosis is an innate antibacterial mechanism.

Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved.