Ten-year trends in opioid prescribing and vaso-occlusive crises in sickle cell disease: a population-based national cohort study (2011-2022).

Background: Patterns of opioid prescribing and vaso-occlusive crises (VOCs) are poorly characterized among individuals with sickle cell disease (SCD) across diverse insurance types and age groups. We aimed to evaluate opioid prescribing and VOC trends in publicly and commercially insured individuals with SCD over a 10-year time period in the United States (US).

Methods: We conducted a retrospective cohort study of US administrative claims (2011-2022), analyzing 45,726 commercial and Medicaid beneficiaries with SCD.

Neural networks of the mouse visceromotor cortex.

The medial prefrontal cortex (MPF) regulates autonomic and neuroendocrine responses to stress and coordinates goal-directed behaviours such as attention, decision-making and social interactions. However, the underlying mechanisms remain unclear due to incomplete circuit-level MPF characterization. Here, using integrated neuroanatomical, physiological and behavioural approaches, we construct a comprehensive wiring diagram of the MPF, focused on the dorsal peduncular area (DP)-a poorly understood prefrontal area.

Age-Related Effects of Cannabis and Cannabinoids on Brain and Behavior.

The effect of cannabis use on health is likely to depend on individual differences. In particular, there is a growing need to understand the impact of cannabis and delta-9-tetrahydrocannabinol (THC) on brain and behavioral health across the lifespan. We conducted a narrative review summarizing the effects of cannabis and THC across three stages of life: , adolescence, and late adulthood.

Elucidating interplay between myrcene and cannabinoid receptor 1 receptors to produce antinociception in mouse models of neuropathic pain.

The need for nonaddictive and effective treatments for chronic pain are at an all-time high. Historical precedence, and now clinical evidence, supports the use of cannabis for alleviating chronic pain. A plethora of research on delta-9-tetrahydrocannabinol exists, yet cannabis is comprised of a multitude of constituents, some of which possess analgesic potential, that have not been systematically investigated, including the terpene myrcene.

Non-Linear Relationships of Loneliness with Age in People Living with Schizophrenia and Non-Psychiatric Comparison Participants: Relations non linéaires entre la solitude et l'âge chez les personnes atteintes de schizophrénie et les personnes n'ayant aucun antécédent de maladie psychiatrique.

Objective: Loneliness – distress that arises from discrepancies between perceived and desired relationships – is increasingly prevalent and recognized as a major public health concern due to the association with negative health outcomes. People living with schizophrenia (PLWS) experience higher rates of loneliness than the general population and may be particularly vulnerable to these adverse outcomes. In the general population, loneliness fluctuates throughout the lifespan, but the relationship between loneliness and age in PLWS is not well understood.

A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection.

The universally conserved α-oxoaldehydes glyoxal (GO) and methylglyoxal (MGO) are toxic metabolic byproducts whose accumulation can lead to cell death. In the absence of a known, natural inducer of the GO-specific response in prokaryotes, we exploited RNA-seq to define a GO response in the bacterial pathogen Pseudomonas aeruginosa. The highest upregulated operon consisted of the known glyoxalase (gloA2) and an antibiotic monooxygenase (ABM) domain of unknown function - renamed here Aldehyde responsive quorum-sensing Inhibitor (ArqI).

Ventricular Repolarization in Healthy Young Adults Who Use Combusted Cannabis: A Cross-Sectional Parallel Group Comparison Study.

Background: Inhaled combusted cannabis and co-use of combusted cannabis and nicotine electronic cigarettes (ECIGs) are emerging trends among young adults, yet the potential cardiovascular disease risks associated with these substances remain unclear. This study examined whether cannabis use increases cardiovascular disease risk, specifically, arrhythmia risk, as estimated by ventricular repolarization, and whether ECIG co-use further amplifies this risk.

Methods: A cross-sectional parallel group comparison study was conducted with 3 groups: healthy adults (21-30 years) who (1) chronically use combusted cannabis but no tobacco, (2) chronically co-use both nicotine ECIGs and combusted cannabis, and (3) are nonusers (controls).

Human development, inequality, and their associations with brain structure across 29 countries.

Background: The macro-social and environmental conditions in which people live, such as the level of a country's development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.

In situ insights into antibody-mediated neutralization of a pre-fusion Junin virus glycoprotein complex.

A transmembrane glycoprotein complex (GPC) decorates the Junin mammarenavirus (JUNV) that causes New World hemorrhagic fevers. We leveraged single-particle cryoelectron microscopy (cryo-EM) to image the full-length JUNV GPC directly on pseudotyped virus (PV) membranes and bound by two JUNV-neutralizing antibodies: Candid#1 vaccine-elicited CR1-28 and J199, a potent therapeutic against Argentine hemorrhagic fever (AHF). The 3.

Multiregional representations of intertemporal decision making in human single neurons.

Understanding the neural mechanisms underlying delay discounting-the tendency to prefer smaller, immediate rewards over larger, delayed rewards-is critical for elucidating the etiology of impulsive decision-making, a hallmark of several psychiatric conditions including substance use and impulse control disorders. Here, we investigate single-neuron activity in the orbitofrontal cortex (OFC), hippocampus, and amygdala of nine human participants performing a delay discounting task. Intracranial recordings yielded a total of 193 single units (50 OFC, 68 amygdala, and 75 hippocampus) and reveal distinct neural correlates of decision-making, including representations of choice preferences and decision difficulty across all three regions.

Mobile EEG examination of putative biomarkers of mental health in individuals that use cannabis.

Healthy individuals that use cannabis are at greater risk of developing mental health conditions than those that do not use cannabis. Here, using mobile electroencephalography (EEG) in controlled laboratory settings, we examined two putative biomarkers of mental health across two studies of people who use cannabis ( = 100, 50% male;  = 40, 60% male). We examined associations to cannabis use and mood and assessed the influence of sex and age on the outcomes.

Opposing effects of mu opioid receptors on dopamine D1 and D2 receptor expressing neurons in opioid mediated antinociception.

There is extensive interaction between systems involved in pain processing and motivation, where the aberrant functioning of salience circuits likely contributes to chronic pain, as well as increased susceptibility to opioid misuse and opioid use disorder. This study asks to what extent mu opioid receptors (MORs) in dopamine D1 receptor (D1R), D2 receptor (D2R) or adenosine A2a receptor (A2aR) expressing neurons contribute to the expression of pain and opioid antinociception. We ablated MORs in dopamine receptor expressing neurons by breeding D1R, D2R or A2aR-cre with MOR mice, which was confirmed by RNAscope multiplex fluorescent in situ hybridization.

Subjective drug-effect ratings predict cannabis self-administration in people who use cannabis daily.

As interest in the potential therapeutic benefits of cannabis-derived products grows, accurate predictors of abuse potential will be vital for informing regulatory decisions. Currently, the Food and Drug Administration recommends using subjective effect ratings of Drug Liking as the primary measure in human abuse potential studies. However, dissociations between subjective ratings and drug-taking behavior have been previously reported.

Physical activity affects DNA methylation-derived inflammation markers in a community-based Parkinson's disease study.

Introduction: Past studies have connected physical activity (PA) and Parkinson's disease (PD) to chronic inflammation. We use DNA methylation-derived (DNAm) proxies for inflammation to investigate the relationship between PA and chronic inflammation among PD patients.

Methods: We collected demographics, lifestyle, and PA status information by interviewing 555 PD patients enrolled in the Parkinson's Environment and Gene (PEG) studies.

A transdiagnostic approach to understanding neural responsivity to reward and its links to social motivation.

Schizophrenia (SZ) and bipolar disorder (BD) are characterized by social impairments. Social impairment also occurs in the general community. Across clinical and nonclinical groups social impairment may be related to deficits in social approach and/or social avoidance motivation.

Effects of virtual reality on spatiotemporal gait parameters and freezing of gait in Parkinson's disease.

Virtual reality (VR) is increasingly used to study freezing of gait (FOG) in Parkinson's disease (PD). However, overground gait in VR typically exhibits shorter, wider, and slower steps than real-world gait in both healthy and PD populations. This altered gait behavior raises the question of whether VR also alters the FOG phenomenon.

Peripheral Alzheimer's Disease Biomarkers Are Related to Change in Subjective Memory in Older Women with Cardiovascular Risk Factors in a Trial of Yoga vs. Memory Training: Lien établi entre les biomarqueurs périphériques de la maladie d'Alzheimer et l'amélioration de la mémoire subjective chez les femmes âgées présentant des facteurs de risque cardiovasculaire dans le cadre d'un essai comparant le yoga à l'entraînement de la mémoire.

Objectives: Older women with cardiovascular risk factors and subjective memory complaints are at greater risk for Alzheimer’s disease (AD). We examined the changes in AD peripheral biomarkers, including phosphorylated-tau (p-tau), Aβ40, Aβ42, and Aβ42/40 ratio, in a randomized controlled trial of Kundalini yoga (KY) versus memory enhancement training (MET) in aging women at risk for AD.

Methods: We recruited women (50+ years) with subjective memory complaints and high cardiovascular risk as defined by the ACC/AHA Guideline on the Assessment of Cardiovascular Risk.

Barriers and delays to healthcare at time of death: qualitative analysis of Los Angeles County death records of people experiencing homelessness.

Background: Human health and homelessness are incompatible with one another. People experiencing homelessness (PEH) experience extreme health and social inequities, including a significantly higher mortality rate and lower life expectancy compared to the general adult population. While many studies have attempted to identify the most common causes of death, no study to our knowledge has sought to contextualize these deaths using death records.

Neural Networks of the Mouse Primary Visceromotor Cortex.

The medial prefrontal cortex (MPF) regulates emotions, stress responses, and goal-directed behaviors like attention and decision-making. However, the precise mechanisms underlying MPF function remain poorly understood, largely due to an incomplete characterization of its neural circuitry. Leveraging neuroanatomical, neurophysiological, and behavioral techniques, we present a detailed wiring diagram of the MPF, with a particular focus on the dorsal peduncular area (DP), an underexplored MPF area implicated in psychological stress, fear conditioning, anxiety, depression, and opioid addiction.

Insomnia and Inflammation Conspire to Heighten Depression Risk: Implications for Treatment and Prevention of Mood Disorders.

Insomnia is ubiquitous, is comorbid with all major mental disorders, increases the risk of depression, and contributes to inflammatory morbidity and all-cause mortality. This review examines the relationships between insomnia and inflammation in the pathophysiology of depression. The unique role of insomnia on depression risk is examined with interrogation of what aspects of sleep disturbance contribute to depressed mood.

Racial Differences in Naturalistic Psychedelic Use - Motivations for Use, Communication with Health Care Providers, and Outcomes.

People of Color have been under-included in psychedelic-assisted therapy (PAT) research. Researchers have argued that systemic issues resulting in harms to communities of color like the War on Drugs and recurrent exposure to discrimination in healthcare settings may reduce their willingness to engage in PAT research. However, there are no empirical data regarding People of Color's trust or willingness in using psychedelics with support of trained healthcare providers.

The Science of Tai Chi and Qigong as Whole Person Health-Part II: Evidence Gaps and Opportunities for Future Research and Implementation.

The emerging paradigm of whole person health shares many core principles with traditional complementary and integrative health frameworks, including Tai Chi and Qigong (TCQ). In the fall of 2023, the Harvard Medical School Osher Center for Integrative Health hosted the inaugural international conference on : at Harvard Medical School. A two-part white paper was written to summarize key conference topics, findings, and issues.

High-Potency Cannabis Use and Health: A Systematic Review of Observational and Experimental Studies.

Objective: Amid continuously rising concentrations of delta-9-tetrahydrocannabinol (THC) in cannabis (i.e., potency), high-potency cannabis is a major topic in contemporary cannabis policy discussions, yet its impact on health is not well understood.