How the APHA Maternal and Child Health Section Advanced the Public Health Approach to Gun Violence Prevention.

Purpose: This manuscript provides a history of efforts by the American Public Health Association (APHA) Maternal and Child Health Section (MCH Section) Gun Violence Prevention Workgroup (GVP Workgroup) to promote gun violence prevention (GVP) as a key public health priority both within the MCH Section and APHA, and nationally.

Description: The MCH Section established a gun violence prevention workgroup in response to the murders of twenty first-grade children and six adults at Sandy Hook Elementary School. This article presents an overview of the accomplishments and challenges of the MCH Section GVP Workgroup in a context of ever-increasing gun violence.

Empowering Voices: Inspiring Women in Medicinal Chemistry.

As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists.

Empowering Voices: Inspiring Women in Medicinal Chemistry.

As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists.

Health Conditions and Treatment Utilization Among Older Male Veterans Incarcerated in Prisons.

Background: More than 50,000 older male veterans incarcerated in prisons are expected to return to their communities and utilize the Veterans Health Administration (VHA) and community healthcare systems. To support the continuity of healthcare and overall successful community reentry of older incarcerated veterans, an understanding of their health profiles and treatment utilization while in correctional care is needed.

Objective: To assess the health status of older male veterans incarcerated in state prisons and explore demographic, military, and VHA-related factors associated with medical conditions, disabilities, behavioral conditions, and medical and behavioral treatment utilization.

Discovery of pyrrolo[2,1-][1,2,4]triazine-based inhibitors of adaptor protein 2-associated kinase 1 for the treatment of pain.

Adaptor protein 2-associated kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and plays a role in modulating receptor endocytosis. AAK1 was identified as a potential therapeutic target for the treatment of neuropathic pain when it was shown that AAK1 knock out (KO) mice had a normal response to the acute pain phase of the mouse formalin model, but a reduced response to the persistent pain phase. Herein we report our early work investigating a series of pyrrolo[2,1-][1,2,4]triazines as part of our efforts to recapitulate this KO phenotype with a potent, small molecule inhibitor of AAK1.

Co-occurring Medical Multimorbidity, Mental Illness, and Substance Use Disorders Among Older Criminal Legal System-Involved Veterans.

Background: Older veterans involved in the criminal legal system (CLS) may have patterns of multimorbidity that place them at risk for poor health outcomes.

Objectives: To estimate the prevalence of medical multimorbidity (≥2 chronic medical diseases), substance use disorders (SUDs), and mental illness among CLS-involved veterans aged 50 and older.

Research Design: Using Veterans Health Administration health records, we estimated the prevalence of mental illness, SUD, medical multimorbidity, and the co-occurrence of these conditions among veterans by CLS involvement as indicated by Veterans Justice Programs encounters.

Enhancing the Visibility of Women in the ACS Division of Medicinal Chemistry (ACS MEDI).

On the occasion of the 2023 International Women's Day on March 8, 2023, we want to celebrate and highlight the contributions of many women volunteers in the American Chemical Society Division of Medicinal Chemistry (ACS MEDI).

Enhancing the Visibility of Women in the ACS Division of Medicinal Chemistry (ACS MEDI).

On the occasion of the 2023 International Women's Day on March 8, 2023, we want to celebrate and highlight the contributions of many women volunteers in the American Chemical Society Division of Medicinal Chemistry (ACS MEDI).

Dementia in the incarcerated population: a retrospective study using the South Carolina Alzheimer's disease registry, USA.

Purpose: Research about the prevalence of dementia among older adults in the incarceration system is currently lacking, and further investigation is warranted. Considering the high level of healthcare needs, unique behavioural issues and difficulty to rehabilitate within the system due to its punitive approach and lack of effective rehabilitation programs, further investigation is warranted to characterize and determine the number of incarcerated older adults with dementia. The purpose of this study is to estimate the prevalence of individuals with dementia in the prison system while also describing the incarceration, demographic and offence-related characteristics of this unique population.

Fusarioid community diversity associated with conifer seedlings in forest nurseries across the contiguous USA.

Introduction: Fusarioid fungi that cause damping-off and root diseases can result in significant losses to conifer crops produced in forest nurseries across the USA. These nurseries are vital to reforestation and forest restoration efforts. Understanding the diversity of Fusarioid fungi associated with damping-off and root diseases of conifer seedlings can provide an approach for targeted management techniques to limit seedling losses and pathogen spread to novel landscapes.

Discovery of ()-1-((2',6-Bis(difluoromethyl)-[2,4'-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (BMS-986176/LX-9211): A Highly Selective, CNS Penetrable, and Orally Active Adaptor Protein-2 Associated Kinase 1 Inhibitor in Clinical Trials for the Treatment of Neuropathic Pain.

Recent mouse knockout studies identified adapter protein-2 associated kinase 1 (AAK1) as a viable target for treating neuropathic pain. Potent small-molecule inhibitors of AAK1 have been identified and show efficacy in various rodent pain models. ()-1-((2',6-Bis(difluoromethyl)-[2,4'-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (BMS-986176/LX-9211) () was identified as a highly selective, CNS penetrant, potent AAK1 inhibitor from a novel class of bi(hetero)aryl ethers.

Bicyclic Heterocyclic Replacement of an Aryl Amide Leading to Potent and Kinase-Selective Adaptor Protein 2-Associated Kinase 1 Inhibitors.

Adaptor protein 2-associated kinase 1 (AAK1) is a serine/threonine kinase that was identified as a therapeutic target for the potential treatment of neuropathic pain. Inhibition of AAK1 in the central nervous system, particularly within the spinal cord, was found to be the relevant site for achieving an antinociceptive effect. We previously reported that compound is a brain-penetrant, AAK1 inhibitor that showed efficacy in animal models for neuropathic pain.

Effects of Different Types of Childhood Victimization on Health Outcomes: A Study of African American Young Adults in Washington, D.C.

Objective: Some children experience violence and trauma with effects lasting into adulthood. We examine how five types of childhood exposure to violence (ETV) affect the current depression, sleep habits, and drug use of 638 African American youth ages 18 to 25, in Washington, D.C.

Exposure to personal and community violence and associated drug use outcomes in African American young adults.

Background: Exposure to violence (ETV) during one's life has been associated with increased risk for substance abuse. Adolescent ETV is also related to substance abuse into adulthood, and has been shown to have a cumulative effect. This study adds to the understanding of how ETV relates to a range of substance use outcomes by specifying how different types of violence affects substance use behaviors in African American young adults, and examines how this exposure is moderated by other life stressors, and health and social experiences.

Violence Exposure, Drug Use and HIV/AIDS Risk Taking Behaviors: The Role of Gender.

Objective: To examine gender differences among African American young adults in their exposure to violence (ETV) before age 18 and community violence as an adult, and the relationship of these exposures to drug use and HIV risk taking behaviors (HIVRTB).

Method: We detail these experiences in 440 self-identified African Americans, ages 18 to 25, from socio-economically disadvantaged wards in Washington, DC. Factor analysis was used to identify the types of violence experienced before age 18 and as adults.

Discovery of VU2957 (Valiglurax): An mGlu Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease.

Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive and pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies.

The discovery of VU0652957 (VU2957, Valiglurax): SAR and DMPK challenges en route to an mGlu PAM development candidate.

This letter describes the first account of the chemical optimization (SAR and DMPK profiling) of a new series of mGlu positive allosteric modulators (PAMs), leading to the identification of VU0652957 (VU2957, Valiglurax), a compound profiled as a preclinical development candidate. Here, we detail the challenges faced in allosteric modulator programs (e.g.

Veterans in Prison for Sexual Offenses: Characteristics and Reentry Service Needs.

Among prison-incarcerated men in the United States, more veterans (35%) have a sexual offense conviction than nonveterans (23%). Limited research has investigated factors explaining the link between military service and sexual offending. Nationally representative data from prison-incarcerated men ( = 14,080) were used to examine the association between veteran status and sexual offenses, adjusting for demographic, childhood, and clinical characteristics.

Discovery and characterization of N-(1,3-dialkyl-1H-indazol-6-yl)-1H-pyrazolo[4,3-b]pyridin-3-amine scaffold as mGlu positive allosteric modulators that mitigate CYP1A2 induction liability.

Previous reports from our laboratory disclosed the structure and activity of a novel 1H-pyrazolo[4,3-b]pyridine-3-amine scaffold (VU8506) which showed excellent potency, selectivity and in vivo efficacy in preclinical rodent models of Parkinson's disease. Unfortunately, this compound suffered from significant CYP1A2 induction as measured through upstream AhR activation (125-fold) and thus was precluded from further advancement in chronic studies. Herein, we report a new scaffold developed recently which was systematically studied in order to mitigate the CYP1A2 liabilities presented in the earlier scaffolds.

BMS-986163, a Negative Allosteric Modulator of GluN2B with Potential Utility in Major Depressive Disorder.

There is a significant unmet medical need for more efficacious and rapidly acting antidepressants. Toward this end, negative allosteric modulators of the -methyl-d-aspartate receptor subtype GluN2B have demonstrated encouraging therapeutic potential. We report herein the discovery and preclinical profile of a water-soluble intravenous prodrug BMS-986163 () and its active parent molecule BMS-986169 (), which demonstrated high binding affinity for the GluN2B allosteric site ( = 4.

Preclinical Characterization of ()-3-((3,4)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (BMS-986169), a Novel, Intravenous, Glutamate -Methyl-d-Aspartate 2B Receptor Negative Allosteric Modulator with Potential in Major Depressive Disorder.

()-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (BMS-986169) and the phosphate prodrug 4-((3,4)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl dihydrogen phosphate (BMS-986163) were identified from a drug discovery effort focused on the development of novel, intravenous glutamate -methyl-d-aspartate 2B receptor (GluN2B) negative allosteric modulators (NAMs) for treatment-resistant depression (TRD). BMS-986169 showed high binding affinity for the GluN2B subunit allosteric modulatory site (K = 4.03-6.

Discovery of non-zwitterionic aryl sulfonamides as Na1.7 inhibitors with efficacy in preclinical behavioral models and translational measures of nociceptive neuron activation.

Since zwitterionic benzenesulfonamide Na1.7 inhibitors suffer from poor membrane permeability, we sought to eliminate this characteristic by replacing the basic moiety with non-basic bicyclic acetals and monocyclic ethers. These efforts led to the discovery of the non-zwitterionic aryl sulfonamide 49 as a selective Na1.