Assessing experts' perspectives on challenges in substance misuse prevention, harm reduction, and treatment to shape funding priorities in New York State.

Background: Drug overdose is a leading cause of death and opioid-related deaths increased by more than 300% from 2010 to 2020 in New York State. Experts holding a range of senior leadership positions from across New York State were asked to identify the greatest challenges in substance misuse prevention, harm reduction, and treatment continuum of care. Expert input was used to shape funding priorities.

Comparison of 30-day retention in treatment among patients referred to opioid use disorder treatment from emergency department and telemedicine settings.

Introduction: Telemedicine is a feasible alternative to in-person evaluations for people with opioid use disorder (OUD). The literature on medications for opioid use disorder (MOUD) telemedicine has focused on ongoing OUD treatment. Emergency department (ED) visits are an opportunity to initiate MOUD; however, little is known regarding the outcomes of patients following telemedicine referrals for MOUD from emergency settings.

Characteristics of Patients Presenting at an Emergency Department for a Heroin Overdose vs Detoxification.

Purpose: This study compares substance use, treatment histories, and sociodemographic characteristics of patients presenting to an emergency department (ED) following a heroin overdose or seeking detoxification services for heroin and examines risk factors for a subsequent return to the ED for a substance-related problem.

Methods: A convenience sample of patients presenting for an overdose or detoxification at an urban teaching ED was recruited for this study. During their ED visit, patients were interviewed regarding demographics, substance use experiences, and treatment history.

COVID-19-Induced Phlegmasia Cerulea Dolens.

A 44-year-old male with a history of deep venous thrombosis (DVT) and pulmonary embolism (PE) with the inferior vena cava (IVC) filter in place and peripheral vascular disease (PVD) status post lower extremity vascular stenting presented from a COVID-19 rehabilitation center with bilateral phlegmasia cerulea dolens and no palpable popliteal or dorsalis pedis pulses, at risk for venous gangrene and loss of limbs. The patient was anticoagulated and taken emergently to the operating room for vascular surgery where thrombolysis with alteplase and mechanical thrombectomy were performed. Bilateral thrombolysis infusion catheters were placed for two days.

G protein-coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na/K ATPase activation.

G-coupled somatostatin or α2-adrenergic receptor activation stimulated β-cell NKA activity, resulting in islet Ca fluctuations. Furthermore, intra-islet paracrine activation of β-cell G-GPCRs and NKAs by δ-cell somatostatin secretion slowed Ca oscillations, which decreased insulin secretion. β-cell membrane potential hyperpolarization resulting from G-GPCR activation was dependent on NKA phosphorylation by Src tyrosine kinases.

Implementing a Novel Statewide Network to Support Emergency Department-initiated Buprenorphine Treatment.

Introduction: Medications for opioid use disorder (MOUD), including buprenorphine, represent an evidence-based treatment that supports long-term recovery and reduces risk of overdose death. Patients in crisis from opioid use disorder (OUD) often seek care from emergency departments (ED). The New York Medication for Addiction Treatment and Electronic Referrals (MATTERS) network is designed to support ED-initiated buprenorphine and urgent referrals to long-term care for patients suffering from OUD.

Liraglutide increases islet Ca oscillation frequency and insulin secretion by activating hyperpolarization-activated cyclic nucleotide-gated channels.

Aim: To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels impact glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) modulation of islet Ca handling and insulin secretion.

Methods: The impact of liraglutide (GLP-1 analogue) on islet Ca handling, HCN currents and insulin secretion was monitored with fluorescence microscopy, electrophysiology and enzyme immunoassays, respectively. Furthermore, liraglutide-mediated β-to-δ-cell cross-communication was assessed following selective ablation of either mouse islet δ or β cells.

iMicrobe: Tools and data-dreaiven discovery platform for the microbiome sciences.

Background: Scientists have amassed a wealth of microbiome datasets, making it possible to study microbes in biotic and abiotic systems on a population or planetary scale; however, this potential has not been fully realized given that the tools, datasets, and computation are available in diverse repositories and locations. To address this challenge, we developed iMicrobe.us, a community-driven microbiome data marketplace and tool exchange for users to integrate their own data and tools with those from the broader community.

Impact of shift duration on alertness among air-medical emergency care clinician shift workers.

Background: Greater than half of Emergency Medical Services (EMS) shift workers report fatigue at work and most work long duration shifts. We sought to compare the alertness level of EMS shift workers by shift duration.

Methods: We used a multi-site, 14-day prospective observational cohort study design of EMS clinician shift workers at four air-medical EMS organizations.

A MicroRNA-29 Mimic (Remlarsen) Represses Extracellular Matrix Expression and Fibroplasia in the Skin.

MicroRNA-29 (miR-29) negatively regulates fibrosis and is downregulated in multiple fibrotic organs and tissues, including in the skin. miR-29 mimics prevent pulmonary fibrosis in mouse models but have not previously been tested in the skin. This study aimed to identify pharmacodynamic biomarkers of miR-29 in mouse skin, to translate those biomarkers across multiple species, and to assess the pharmacodynamic activity of a miR-29b mimic (remlarsen) in a clinical trial.

Real-Time Fatigue Mitigation with Air-Medical Personnel: The SleepTrackTXT2 Randomized Trial.

The aims of this study were: 1) to determine the short-term impact of the SleepTrackTXT2 intervention on air-medical clinician fatigue during work shifts and 2) determine the longer-term impact on sleep quality over 120 days. We used a multi-site randomized controlled trial study design with a targeted enrollment of 100 (ClinicalTrials.gov NCT02783027).

Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma.

miR-155, a microRNA associated with poor prognosis in lymphoma and leukaemia, has been implicated in the progression of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). In this study, we developed and tested cobomarsen (MRG-106), a locked nucleic acid-modified oligonucleotide inhibitor of miR-155. In MF and human lymphotropic virus type 1 (HTLV-1+) CTCL cell lines in vitro, inhibition of miR-155 with cobomarsen de-repressed direct miR-155 targets, decreased expression of multiple gene pathways associated with cell survival, reduced survival signalling, decreased cell proliferation and activated apoptosis.

HOMINID: a framework for identifying associations between host genetic variation and microbiome composition.

Recent studies have uncovered a strong effect of host genetic variation on the composition of host-associated microbiota. Here, we present HOMINID, a computational approach based on Lasso linear regression, that given host genetic variation and microbiome taxonomic composition data, identifies host single nucleotide polymorphisms (SNPs) that are correlated with microbial taxa abundances. Using simulated data, we show that HOMINID has accuracy in identifying associated SNPs and performs better compared with existing methods.

Fatigue mitigation with SleepTrackTXT2 in air medical emergency care systems: study protocol for a randomized controlled trial.

Background: Most air medical Emergency Medical Services (EMS) clinicians work extended duration shifts, and more than 50% report inadequate sleep, poor sleep quality, and/or poor recovery between shifts. The SleepTrackTXT pilot trial (ClinicalTrials.gov, NCT02063737) showed that use of mobile phone text messages could impact EMS clinician self-reported fatigue and sleepiness during long duration shifts.

The Efficacy of Cardiac Anti-miR-208a Therapy Is Stress Dependent.

MicroRNAs (miRNAs) are important regulators of biology and disease. Recent animal efficacy studies validate the therapeutic benefit of miRNA modulation and underscore the therapeutic value of miRNA-targeting oligonucleotides. However, whether disease conditions (stress) influence the pharmacological effects of an anti-miR is currently unknown.

Variation in Rural African Gut Microbiota Is Strongly Correlated with Colonization by Entamoeba and Subsistence.

The human gut microbiota is impacted by host nutrition and health status and therefore represents a potentially adaptive phenotype influenced by metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that industrialization is strongly correlated with patterns in human gut microbiota; however, we know little about the relative contribution of factors such as climate, diet, medicine, hygiene practices, host genetics, and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i) contrast the gut microbiota of populations inhabiting similar environments but having different traditional subsistence modes and either shared or distinct genetic ancestry, and (ii) examine the relationship between gut parasites and bacterial communities.

Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment.

Background: The human gut microbiome is associated with the development of colon cancer, and recent studies have found changes in the microbiome in cancer patients compared to healthy controls. Studying the microbial communities in the tumor microenvironment may shed light on the role of host-bacteria interactions in colorectal cancer. Here, we highlight the major shifts in the colorectal tumor microbiome relative to that of matched normal colon tissue from the same individual, allowing us to survey the microbial communities in the tumor microenvironment and providing intrinsic control for environmental and host genetic effects on the microbiome.

Restriction Site-Associated DNA Sequencing (RAD-seq) Reveals an Extraordinary Number of Transitions among Gecko Sex-Determining Systems.

Sex chromosomes have evolved many times in animals and studying these replicate evolutionary "experiments" can help broaden our understanding of the general forces driving the origin and evolution of sex chromosomes. However this plan of study has been hindered by the inability to identify the sex chromosome systems in the large number of species with cryptic, homomorphic sex chromosomes. Restriction site-associated DNA sequencing (RAD-seq) is a critical enabling technology that can identify the sex chromosome systems in many species where traditional cytogenetic methods have failed.

Delta-6-desaturase links polyunsaturated fatty acid metabolism with phospholipid remodeling and disease progression in heart failure.

Background: Remodeling of myocardial phospholipids has been reported in various forms of heart failure for decades, but the mechanism and pathophysiological relevance of this phenomenon have remained unclear. We examined the hypothesis that δ-6 desaturase (D6D), the rate-limiting enzyme in long-chain polyunsaturated fatty acid biosynthesis, mediates the signature pattern of fatty acid redistribution observed in myocardial phospholipids after chronic pressure overload and explored plausible links between this process and disease pathogenesis.

Methods And Results: Compositional analysis of phospholipids from hearts explanted from patients with dilated cardiomyopathy revealed elevated polyunsaturated fatty acid product/precursor ratios reflective of D6D hyperactivity, manifesting primarily as lower levels of linoleic acid with reciprocally higher levels of arachidonic and docosahexaenoic acids.

Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure.

Aims: Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in hypertension-induced heart disease.

Methods And Results: In order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure.