APPROACH e-PROM system: a user-centered development and evaluation of an electronic patient-reported outcomes measurement system for management of coronary artery disease.

Background: Coronary artery disease (CAD) confers increased risks of premature mortality, non-fatal morbidity, and significant impairment in functional status and health-related quality of life. Routine administration of electronic patient-reported outcome measures (PROMs) and its real time delivery to care providers is known to have the potential to inform routine cardiac care and to improve quality of care and patient outcomes. This study describes a user-centered development and evaluation of the Alberta Provincial Project for Outcomes Assessment (APPROACH) electronic Patient Reported Outcomes Measurement (e-PROM) system.

Dysregulation of kappa opioid receptor neuromodulation of lateral habenula synaptic function following a repetitive mild traumatic brain injury.

Mild traumatic brain injury (mTBI) increases the risk of affective disorders, anxiety and substance use disorder. The lateral habenula (LHb) plays an important role in pathophysiology of psychiatric disorders. Recently, we demonstrated a causal link between mTBI-induced LHb hyperactivity due to excitation/inhibition (E/I) imbalance and motivational deficits in male mice using a repetitive closed head injury mTBI model.

Effects of Repetitive Mild Traumatic Brain Injury on Corticotropin-Releasing Factor Modulation of Lateral Habenula Excitability and Motivated Behavior.

Mild traumatic brain injury (mTBI) is a significant health burden due to mTBI-related chronic debilitating cognitive and psychiatric morbidities. Recent evidence from our laboratory suggests a possible dysregulation within reward/motivational circuit function at the level of a subcortical structure, the lateral habenula (LHb), where we demonstrated a causal role for hyperactive LHb in mTBI-induced motivational deficits in self-care grooming behavior in young adult male mice when exposed to mTBI during late adolescence (at ∼8 weeks old). In this study, we extended this observation by further characterizing neurobehavioral effects of this repetitive closed head injury model of mTBI in both young adult male and female mice on LHb excitability, corticotropin releasing factor (CRF) modulation of LHb activity, and behavioral responses of motivation to self-care behavior and approach versus avoidance behavior in the presence of a social- or threat-related stimulus.

Estimated Effectiveness of the BNT162b2 XBB Vaccine Against COVID-19.

Importance: Data describing the early additional protection afforded by the recently recommended BNT162b2 XBB vaccine (Pfizer-BioNTech; 2023-2024 formulation) are limited.

Objective: To estimate the association between receipt of the BNT162b2 XBB vaccine and medically attended COVID-19 outcomes among US adults 18 years and older.

Design, Setting, And Participants: This test-negative case-control study was performed to estimate the effectiveness of the BNT162b2 XBB vaccine against COVID-19-associated hospitalization and emergency department (ED) or urgent care (UC) encounters among adults in the Kaiser Permanente Southern California health system between October 10, 2023, and December 10, 2023.

Effects of Repetitive Mild Traumatic Brain Injury on Corticotropin-Releasing Factor Modulation of Lateral Habenula Excitability and Motivated Behavior.

Mild traumatic brain injury (mTBI) is a significant health burden due to mTBI-related chronic debilitating cognitive and psychiatric morbidities. Recent evidence from our laboratory suggests a possible dysregulation within reward/motivational circuit function at the level of a subcortical structure, the lateral habenula (LHb), where we demonstrated a causal role for hyperactive LHb in mTBI-induced motivational deficits in self-care grooming behavior in young adult male mice when exposed to mTBI injury during late adolescence (at ~8 weeks old). Here we extended this observation by further characterizing neurobehavioral effects of this repetitive closed head injury model of mTBI in both young adult male and female mice on LHb excitability, corticotropin releasing factor (CRF) modulation of LHb activity, and behavioral responses of motivation to self-care behavior, and approach versus avoidance behavior in the presence of a social- or threat-related stimulus.

Intensive Aerobic Cycling Is Feasible and Elicits Improvements in Gait Velocity in Individuals With Multiple Sclerosis: A Preliminary Study.

Background: Aerobic exercise (AEx) has many potential benefits; however, it is unknown whether individuals with multiple sclerosis (MS) can attain the optimal intensity and duration to harness its effects. Forced-rate exercise (FE) is a novel paradigm in which the voluntary pedaling rate during cycling is supplemented to achieve a higher exercise intensity. The aim of this pilot trial was to investigate the feasibility and initial efficacy of a 12-week FE or voluntary exercise (VE) cycling intervention for individuals with MS.

Dysregulation of Kappa Opioid Receptor Neuromodulation of Lateral Habenula Synaptic Function following a Repetitive Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) increases the risk of cognitive deficits, affective disorders, anxiety and substance use disorder in affected individuals. Substantial evidence suggests a critical role for the lateral habenula (LHb) in pathophysiology of psychiatric disorders. Recently, we demonstrated a causal link between persistent mTBI-induced LHb hyperactivity due to synaptic excitation/inhibition (E/I) imbalance and motivational deficits in self-care grooming behavior in young adult male mice using a repetitive closed head injury mTBI model.

AKAP150-anchored PKA regulates synaptic transmission and plasticity, neuronal excitability and CRF neuromodulation in the mouse lateral habenula.

The scaffolding A-kinase anchoring protein 150 (AKAP150) is critically involved in kinase and phosphatase regulation of synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a key role in brain's processing of rewarding/aversive experiences, however its role in the lateral habenula (LHb, as an important brain reward circuitry) is completely unknown. Using whole cell patch clamp recordings in LHb of male wildtype and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), here we show that the genetic disruption of PKA anchoring to AKAP150 significantly reduces AMPA receptor-mediated glutamatergic transmission and prevents the induction of presynaptic endocannabinoid-mediated long-term depression in LHb neurons.

Pilot Implementation of a Nutrition-Focused Community-Health-Worker Intervention among Formerly Chronically Homeless Adults in Permanent Supportive Housing.

Food insecurity is a known health equity threat for formerly chronically homeless populations even after they transition into permanent housing. This project utilized a human-centered design methodology to plan and implement a nutrition-focused community-health-worker (CHW) intervention in permanent supportive housing (PSH). The project aimed to increase access to healthy foods, improve nutritional literacy, healthy cooking/eating practices, and build community/social connectedness among 140 PSH residents.

Aerobic cycling reduces fatigue and improves pain in persons with multiple sclerosis: A preliminary study.

Fatigue and pain are prevalent in persons with multiple sclerosis (PwMS), negatively impacting quality of life (QoL). Clinical management is challenging due to their multiple underlying causes. Aerobic exercise elicits central and peripheral effects, which may effectively manage MS-related symptoms.

Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against a range of COVID-19 outcomes in a large health system in the USA: a test-negative case-control study.

Background: XBB-related omicron sublineages have recently replaced BA.4/5 as the predominant omicron sublineages in the USA and other regions globally. Despite preliminary signs of immune evasion of XBB sublineages, few data exist describing the real-world effectiveness of bivalent COVID-19 vaccines, especially against XBB-related illness.

An miRNA with a major impact on stress.

miRNAs regulate mRNAs, including those important for synapse function in the brain. Mucha and colleagues recently identified a novel miRNA-mRNA interaction in the basolateral amygdala that acts as a homeostatic counter to stress-induced anxiety and synaptic changes, suggesting miRNAs as potential avenues for therapeutic intervention in anxiety disorders.

Assessment of microbial bioburden on portable medical equipment in a hospital setting.

Objectives: Although routine disinfection of portable medical equipment is required in most hospitals, frontline staff may not be able to disinfect portable medical equipment at a rate that adequately maintains low bioburden on high-use equipment. This study quantified bioburden over an extended time period for two types of portable medical equipment, workstations on wheels and vitals machines, across three hospital wards.

Methods: Bioburden was quantified via press plate samples taken from high touch surfaces on 10 workstations on wheels and 5 vitals machines on each of 3 medical surgical units.

BNT162b2 Against COVID-19-Associated Emergency Department and Urgent Care Visits Among Children 5-11 Years of Age: A Test Negative Design.

In a 1:1 matched test-negative design among 5- to 11-year-olds in the Kaiser Permanente Southern California health system (n = 3984), BNT162b2 effectiveness against the omicron-related emergency department or urgent care encounters was 60% [95%CI: 47-69] <3 months post-dose-two and 28% [8-43] after ≥3 months. A booster improved protection to 77% [53-88].

Analysis of mRNA COVID-19 Vaccine Uptake Among Immunocompromised Individuals in a Large US Health System.

Importance: Immunocompromised individuals are at increased risk for severe outcomes due to SARS-CoV-2 infection. Given the varying and complex nature of COVID-19 vaccination recommendations, it is important to understand COVID-19 vaccine uptake in this vulnerable population.

Objective: To assess mRNA COVID-19 vaccine uptake and factors associated with uptake among immunocompromised individuals from December 14, 2020, through August 6, 2022.

Associations of sNfL with clinico-radiological measures in a large MS population.

Objective: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

Methods: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

Effects of prenatal opioid exposure on synaptic adaptations and behaviors across development.

In this review, we focus on prenatal opioid exposure (POE) given the significant concern for the mental health outcomes of children with parents affected by opioid use disorder (OUD) in the view of the current opioid crisis. We highlight some of the less explored interactions between developmental age and sex on synaptic plasticity and associated behavioral outcomes in preclinical POE research. We begin with an overview of the rich literature on hippocampal related behaviors and plasticity across POE exposure paradigms.

Involvement of Lateral Habenula Dysfunction in Repetitive Mild Traumatic Brain Injury-Induced Motivational Deficits.

Affective disorders including depression (characterized by reduced motivation, social withdrawal, and anhedonia), anxiety, and irritability are frequently reported as long-term consequences of mild traumatic brain injury (mTBI) in addition to cognitive deficits, suggesting a possible dysregulation within mood/motivational neural circuits. One of the important brain regions that control motivation and mood is the lateral habenula (LHb), whose hyperactivity is associated with depression. Here, we used a repetitive closed-head injury mTBI model that is associated with social deficits in adult male mice and explored the possible long-term alterations in LHb activity and motivated behavior 10-18 days post-injury.

Repetitive mild traumatic brain injury induces persistent alterations in spontaneous synaptic activity of hippocampal CA1 pyramidal neurons.

Mild traumatic brain injury (mTBI) or concussion is the most common form of TBI which frequently results in persistent cognitive impairments and memory deficits in affected individuals [1]. Although most studies have investigated the role of hippocampal synaptic dysfunction in earlier time points following a single injury, the long-lasting effects of mTBI on hippocampal synaptic transmission following multiple brain concussions have not been well-elucidated. Using a repetitive closed head injury (3XCHI) mouse model of mTBI, we examined the alteration of spontaneous synaptic transmission onto hippocampal CA1 pyramidal neurons by recording spontaneous excitatory AMPA receptor (AMPAR)- and inhibitory GABAR-mediated postsynaptic currents (sEPSCs and sIPSCs, respectively) in adult male mice 2-weeks following the injury.

Lateral Habenula Beyond Avoidance: Roles in Stress, Memory, and Decision-Making With Implications for Psychiatric Disorders.

In this Perspective review, we highlight some of the less explored aspects of lateral habenula (LHb) function in contextual memory, sleep, and behavioral flexibility. We provide evidence that LHb is well-situated to integrate different internal state and multimodal sensory information from memory-, stress-, motivational-, and reward-related circuits essential for both survival and decision making. We further discuss the impact of early life stress (ELS) on LHb function as an example of stress-induced hyperactivity and dysregulation of neuromodulatory systems within the LHb that promote anhedonia and motivational deficits following ELS.