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Peer tutoring in higher education is an effective strategy for promoting academic gains. Within nursing, peer tutoring has been used in the clinical setting, but little information is available regarding its use across the nursing curriculum. A peer tutoring program was created at a regional Appalachian university to meet the needs of students with poor academic backgrounds and multiple risk factors for failure. As the program naturally evolved, students moved beyond the time-honored one-on-one model. Many tutoring patterns developed including dyad, small group, large group, skill based, assignment based, and question based. Qualitative evaluation data from the program revealed that each pattern required different tutor skills, involved varied tutor-tutoree relationships, focused on different outcomes, and had certain advantages and disadvantages. All tutoring patterns contributed to improved academic skills and performance. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by hypermethylation of expanded CGG repeats (>200) in the FMR1 gene leading to gene silencing and loss of Fragile X Messenger Ribonucleoprotein (FMRP) expression. FMRP plays important roles in neuronal function, and loss of FMRP in mouse and human FXS cell models leads to aberrant synaptic signaling and hyperexcitability. Multiple drug candidates have advanced into clinical trials for FXS, but no efficacious treatment has been identified to date, possibly as a consequence of poor translation from pre-clinical animal models to human. Here, we use a high resolution all-optical electrophysiology platform applied to multiple FXS patient-derived and CRISPR/Cas9-generated isogenic neuronal cell lines to develop a multi-parametric FXS disease phenotype. This neurophysiological phenotype was optimized and validated into a high throughput assay based on the amount of FMRP re-expression and the number of healthy neurons in a mosaic network necessary for functional rescue. The resulting highly sensitive and multiparameter functional assay can now be applied as a discovery platform to explore new therapeutic approaches for the treatment of FXS., (© 2024. The Author(s).)

Abstract: Chronic pain associated with osteoarthritis (OA) remains an intractable problem with few effective treatment options. New approaches are needed to model the disease biology and to drive discovery of therapeutics. We present an in vitro model of OA pain, where dorsal root ganglion (DRG) sensory neurons were sensitized by a defined mixture of disease-relevant inflammatory mediators, here called Sensitizing PAin Reagent Composition or SPARC. Osteoarthritis-SPARC components showed synergistic or additive effects when applied in combination and induced pain phenotypes in vivo. To measure the effect of OA-SPARC on neural firing in a scalable format, we used a custom system for high throughput all-optical electrophysiology. This system enabled light-based membrane voltage recordings from hundreds of neurons in parallel with single cell and single action potential resolution and a throughput of up to 500,000 neurons per day. A computational framework was developed to construct a multiparameter OA-SPARC neuronal phenotype and to quantitatively assess phenotype reversal by candidate pharmacology. We screened ∼3000 approved drugs and mechanistically focused compounds, yielding data from over 1.2 million individual neurons with detailed assessment of functional OA-SPARC phenotype rescue and orthogonal "off-target" effects. Analysis of confirmed hits revealed diverse potential analgesic mechanisms including ion channel modulators and other mechanisms including MEK inhibitors and tyrosine kinase modulators. Our results suggest that the Raf-MEK-ERK axis in DRG neurons may integrate the inputs from multiple upstream inflammatory mediators found in osteoarthritis patient joints, and MAPK pathway activation in DRG neurons may contribute to chronic pain in patients with osteoarthritis., (Copyright © 2023 International Association for the Study of Pain.)

Evidence is emerging of the pandemic disproportionately impacting communities of color. This study investigates mental health distress among essential workers during the coronavirus pandemic across race and ethnicity. We evaluate individual responses to the patient health questionnaire and general anxiety disorder questionnaire using a unique, nationally representative data set. Our findings suggest that essential healthcare workers reported the highest rates of mental health distress at the beginning of the coronavirus pandemic. However, when evaluated across race and ethnicity, we find that Black essential healthcare workers disproportionately report symptoms of anxiety; while, Hispanic essential healthcare workers disproportionately report symptoms of depression. Additionally, we find that being a Black or Hispanic essential nonhealthcare worker is associated with higher levels of distress related to anxiety and depression. These findings highlight the additional dimensions to which Black and Hispanic Americans may be disproportionately affected by the coronavirus pandemic. Furthermore, it calls into question how the essential worker classification, compounded by US unemployment policies, is potentially amplifying the mental health distress experienced by workers., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Optogenetic assays provide a flexible, scalable, and information rich approach to probe compound effects for ion channel drug targets in both heterologous expression systems and associated disease relevant cell types. Despite the potential utility and growing adoption of optogenetics, there remains a critical need for compatible platform technologies with the speed, sensitivity, and throughput to enable their application to broader drug screening applications. To address this challenge, we developed the Swarm TM , a custom designed optical instrument for highly parallelized, multicolor measurements in excitable cells, simultaneously recording changes in voltage and calcium activities at high temporal resolution under optical stimulation. The compact design featuring high power LEDs, large numerical aperture optics, and fast photodiode detection enables all-optical individual well readout of 24-wells simultaneously from multi-well plates while maintaining sufficient temporal resolution to probe millisecond response dynamics. The Swarm delivers variable intensity blue-light optogenetic stimulation to enable membrane depolarization and red or lime-light excitation to enable fluorescence detection of the resulting changes in membrane potential or calcium levels, respectively. The Swarm can screen ~10,000 wells/day in 384-well format, probing complex pharmacological interactions via a wide array of stimulation protocols. To evaluate the Swarm screening system, we optimized a series of heterologous optogenetic spiking HEK293 cell assays for several voltage-gated sodium channel subtypes including Nav1.2, Nav1.5, and Nav1.7. The Swarm was able to record pseudo-action potentials stably across all 24 objectives and provided pharmacological characterization of diverse sodium channel blockers. We performed a Nav1.7 screen of 200,000 small molecules in a 384-well plate format with all 560 plates reaching a Z' > 0.5. As a demonstration of the versatility of the Swarm, we also developed an assay measuring cardiac action potential and calcium waveform properties simultaneously under paced conditions using human induced pluripotent stem (iPS) cell-derived cardiomyocytes as an additional counter screen for cardiac toxicity. In summary, the Swarm is a novel high-throughput all-optical system capable of collecting information-dense data from optogenetic assays in both heterologous and iPS cell-derived models, which can be leveraged to drive diverse therapeutic discovery programs for nervous system disorders and other disease areas involving excitable cells., Competing Interests: GB, HZ, BH, JJ, JG, RC, DZ, AB, CW, YL, SN, OM, and GD are current or former employees of Q-State Biosciences and may hold stock options in Q-State Biosciences., (Copyright © 2022 Borja, Zhang, Harwood, Jacques, Grooms, Chantre, Zhang, Barnett, Werley, Lu, Nagle, McManus and Dempsey.)

Importance: Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown., Objective: To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19-related hypoxemia who have not received mechanical ventilation., Design, Setting, and Participants: This pragmatic nonrandomized controlled trial was conducted at 2 academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19-associated hypoxemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020., Interventions: Patients were assigned 1:1 to receive either the practitioner-recommended awake prone positioning intervention (intervention group) or usual care (usual care group)., Main Outcomes and Measures: Primary outcome analyses were performed using a bayesian proportional odds model with covariate adjustment for clinical severity ranking based on the World Health Organization ordinal outcome scale, which was modified to highlight the worst level of hypoxemia on study day 5., Results: A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] were male; and most [417 (83.2%)] were self-reported non-Hispanic or non-Latinx) were included. Baseline severity was comparable between the intervention vs usual care groups, with 170 patients (65.9%) vs 162 patients (66.7%) receiving oxygen via standard low-flow nasal cannula, 71 patients (27.5%) vs 62 patients (25.5%) receiving oxygen via high-flow nasal cannula, and 16 patients (6.2%) vs 19 patients (7.8%) receiving noninvasive positive-pressure ventilation. Nursing observations estimated that patients in the intervention group spent a median of 4.2 hours (IQR, 1.8-6.7 hours) in the prone position per day compared with 0 hours (IQR, 0-0.7 hours) per day in the usual care group. On study day 5, the bayesian posterior probability of the intervention group having worse outcomes than the usual care group on the modified World Health Organization ordinal outcome scale was 0.998 (posterior median adjusted odds ratio [aOR], 1.63; 95% credibility interval [CrI], 1.16-2.31). However, on study days 14 and 28, the posterior probabilities of harm were 0.874 (aOR, 1.29; 95% CrI, 0.84-1.99) and 0.673 (aOR, 1.12; 95% CrI, 0.67-1.86), respectively. Exploratory outcomes (progression to mechanical ventilation, length of stay, and 28-day mortality) did not differ between groups., Conclusions and Relevance: In this nonrandomized controlled trial, prone positioning offered no observed clinical benefit among patients with COVID-19-associated hypoxemia who had not received mechanical ventilation. Moreover, there was substantial evidence of worsened clinical outcomes at study day 5 among patients recommended to receive the awake prone positioning intervention, suggesting potential harm., Trial Registration: ClinicalTrials.gov Identifier: NCT04359797.

Mandatory access Prescription Drug Monitoring Programs (MA-PDMPs) aim to curb the epidemic at a common point of initiation of use, the prescription. However, there is recent concern about whether opioid policies have been too restrictive and reduced appropriate access to patients with the most need for opioid pharmaceuticals. We assess MA-PDMP's effect on specialty-specific opioid prescribing behavior of Medicare providers. Our findings suggest that requiring providers to query a PDMP differentially affects opioid prescribing across provider specialties. We find a three to four percent decrease in prescribing for Primary Care and Internal Medicine providers. This result is driven by healthcare providers at the lower end of the prescribing distribution. There is also suggestive evidence of an increase in opioid use disorder treatment drugs prescribed by these same providers. We also find no evidence for the hypothesis that MA-PDMPs restrict prescribing by providers who treat patients with potentially high levels of pain, few drug substitutes, or urgency for pain treatment (e.g., Oncology/Palliative care). This result is not dependent on whether a state provides exemptions for these providers. Our results indicate that MA-PDMPs may help close provider-patient informational gaps while retaining a provider's ability to supply these drugs to patients with a need for opioids., (© 2021 John Wiley & Sons Ltd.)

Research that explores the role of substance use treatment among older individuals is scarce. This paper offers a historical investigation of admissions and discharges for treatment episodes over the past two decades across race, ethnicity, gender, and age. Our results suggest that although older individuals are not typically associated with risky behavior, they are increasingly seeking treatment for substance use disorders. We find that substance use treatment admissions for people aged 50 and older have persistently increased over our sample period. Our findings also indicate that, on average, Black (relative to white) admissions across all ages are less likely to complete treatment and more likely to have their treatment terminated by a treatment facility. We also find some evidence that Hispanic admissions are relatively less likely to complete treatment across all age groups. Hispanics over 50 years old are also more likely to terminate treatment. Interestingly, among younger individuals in the most recent years of our sample, the disparity between minority completion rates has improved. Lastly, we find that males (relative to females) are more likely to complete a substance use treatment program but no more likely to have their treatment terminated by a substance use treatment facility., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Based on a 6-year, learn and earn curriculum, the authors report on a year-old project that assists licensed practical nurses (LPNs) to obtain a baccalaureate degree in nursing (BSN). Partnerships with 4 area healthcare agencies employing LPNs were developed to support students with full or partial tuition reimbursement and work schedules to accommodate classes. Key university staff in the offices of admissions, financial aid, adult programs and services, and nursing advisement are assigned to this student group to provide individualized assistance. The authors discuss unique components of the project including regularly scheduled role transition seminars, faculty mentors, BSN and nurse practitioner clinical mentors, and clinical experiences in nurse-managed clinics.