Temporal Summation but not Expectations of Pain Relief Predict Response to Acupuncture Treatment in Fibromyalgia.

Fibromyalgia (FM) is a common chronic pain condition for which acupuncture treatment is increasingly utilized. However, there is no universally accepted measure to predict whether a specific patient will benefit from acupuncture. This is a single center, single-blind, sham-controlled, randomized, non-crossover, longitudinal trial of 76 subjects with FM, assigned to either electroacupuncture or a placebo control, mock laser acupuncture. Outcome measures included: clinical pain severity (Brief Pain Inventory, BPI), degree of nociplastic pain (Fibromyalgia Survey Questionnaire, FSQ), and pressure pain tolerance. Baseline measures of temporal summation of pain and expectations for treatment relief were used as predictors. Individuals in both treatment groups experienced significant reductions in BPI (electroacupuncture: p<0.001; mock laser: p=0.018) and FSQ (electroacupuncture: p=0.032; mock laser: p=0.002) after treatment; however, neither group showed a significant increase in pressure pain tolerance. Lower temporal summation at baseline was correlated with greater post-treatment improvement in BPI in the electroacupuncture group (rho=0.389, p=0.025) but not in the mock laser group (rho=-0.272, p=0.109). Lower baseline temporal summation was correlated with greater decreases in pressure pain tolerance following electroacupuncture (rho=0.400, p=0.040), whereas the opposite was seen for mock laser (rho=-0.562, p=0.001). Treatment expectancy at baseline was not correlated with any outcome after electroacupuncture or mock laser treatments. Our results support using a quantitative sensory testing metric, temporal summation of pain, but not expectations, to predict analgesia following acupuncture treatment for pain. CLINICAL TRIAL REGISTRATION: Registered under ClinicalTrials.gov identifier NCT02064296. PERSPECTIVE: A randomized study of acupuncture in fibromyalgia found baseline temporal summation, but not expectations of pain relief, to be predictive of treatment response.

Eliminating rote postoperative radiographs for surgically managed pediatric supracondylar humerus fractures.

BACKGROUND: Use of postoperative radiographs after surgical management of supracondylar humerus (SCH) fractures is often based on rote practice rather than evidence. The purpose of this study was to determine the frequency with which 3-week postoperative radiographs at the time of pin removal altered management plans in pediatric SCH fractures that were intraoperatively stable after closed reduction and percutaneous pinning (CRPP). METHODS: We prospectively recruited pediatric patients with SCH fractures managed by CRPP at our institution from June 2020 until June 2022, and reviewed retrospective data on pediatric SCH fractures managed surgically at our institution between April 2008 and March 2015. Patients were assessed for post-CRPP fracture alignment and stability. For prospective patients, we asked clinicians to document their management decision at the 3-week follow-up visit before evaluating the postoperative radiographs. Our primary outcome was change in management because of radiographic findings. RESULTS: Overall, 1066 patients in the retrospective data and 446 prospectively recruited patients met the inclusion criteria. In the prospective group, radiographic findings altered management for 2 patients (0.4%). One patient had slow callus formation and 1 patient was identified as having cubitus varus. Altered management included prolonged immobilization or additional radiographic follow-up. Radiographic findings altered management in 0 (0%) of 175 type II fractures, in 2 (0.9%) of 221 type III fractures, and in 0 (0%) of 44 type IV fractures. We obtained similar findings from retrospective data. CONCLUSION: Rote use of 3-week postoperative radiographs after surgical management of SCH fractures that are intraoperatively stable has minimal utility. Eliminating rote postoperative radiographs for SCH fractures can decrease the time and financial burdens on families and health care systems without affecting patient outcomes.

Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research. Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research. Results: While transgender individuals represent a significant and increasingly visible component of the population, many researchers and clinicians are not well informed about the diversity in gender identity, physiology, hormonal status, and gender-affirming medical procedures utilized by transgender and other gender diverse patients. Transgender and cisgender people present with many of the same medical concerns, but research and treatment of these medical needs must reflect an appreciation of how differences in sex, gender, gender-affirming medical procedures, and minoritized status impact pain. Conclusions: While significant advances have occurred in our appreciation of pain, the review indicates the need to support more targeted research on treatment and prevention of pain in transgender individuals. This is particularly relevant both for gender-affirming medical interventions and related medical care. Of particular importance is the need for large long-term follow-up studies to ascertain best practices for such procedures. A multi-disciplinary approach with personalized interventions is of particular importance to move forward.

Are We the Problem? A Call to Action for Addressing Institutional Challenges to Engaging Community Partners in Research.

Community-engaged research (CEnR) is a potent tool for addressing health inequities and fostering equitable relationships among communities, researchers, and institutions. CEnR involves collaboration throughout the research process, demonstrating improvements in study recruitment and retention, intervention efficacy, program sustainability, capacity building among partners, and enhanced cultural relevance. Despite the increasing demand for CEnR, institutional policies, particularly human participation protection training (HPP), lag behind, creating institutional barriers to community partnerships. Here, we highlight challenges encountered in our ongoing study, Fostering Opportunities in Research through Messaging and Education (FOR ME), focused on promoting shared decision-making around clinical trial participation among Black women diagnosed with breast cancer. Grounded in CEnR methods, FOR ME has a partnership with a community-based organization (CBO) that addresses the needs of Black women with breast cancer. Our CBO partner attempted to obtain HPP training, which was administratively burdensome and time-consuming. As CEnR becomes more prevalent, academic and research institutions, along with researchers, are faced with a call to action to become more responsive to community partner needs. Accordingly, we present a guide to HPP training for community partners, addressing institutional barriers to community partner participation in research. This guide outlines multiple HPP training pathways for community partners, aiming to minimize institutional barriers and enhance their engagement in research with academic partners.

Community-Based Organizations Leading Research Efforts: Preliminary Findings from the Chicagoland CEAL Program's COVID-19 Vaccine Uptake and Intention Survey.

BACKGROUND: To foster community engaged research in the communities most impacted by COVID-19, the National Institutes of Health (NIH) formed 21 teams of Community Engagement Alliance Against COVID-19 Disparities (CEAL). The national CEAL initiative developed a Common Survey to investigate attitudes and behaviors to the COVID-19 vaccine and clinical trials. This article describes survey implementation at the Chicagoland CEAL Program (CCP). METHODS: This community-based participatory research project was the result of a strong collaboration between academic institutions, and a community-based non-profit health equity-focused partner organization. The survey implementation was developed and refined with strong input from CHWs, participants, and staff in the partner organizations and institutions. Survey data were collected with Qualtrics, a web-based survey tool. RESULTS: Survey implementation resulted in data collection for 852 participants during the period 12/18/2021-02/18/2023. Excluding participants on the basis of missing data resulted in a sample of 690, 601 of which (87.10%) indicated that they had received at least one dose or intended to get vaccinated. Overall, 54 (7.83%) respondents reported that they had not received the vaccine and were not planning to. CONCLUSION: Hard to reach populations present two unique challenges in emerging infectious disease events. Reaching populations vulnerable to poor outcomes with vaccines was essential to addressing the COVID-19 pandemic. Additionally, learning about barriers and hesitancy toward vaccine uptake is difficult in these communities. CCP's partnership of five academic institutions, a community research center, and a community-based non-profit health equity-focused organization shows what is possible when traditional models of research and inquiry are reconsidered for community-based participatory research. Results shown here are drawn from a collaboratively designed and implemented survey, collected in person, with over 90% completion.

Valganciclovir in Infants with Hearing Loss and Clinically Inapparent Congenital Cytomegalovirus Infection: A Nonrandomized Controlled Trial.

OBJECTIVE: To assess the efficacy of valganciclovir in infants with hearing loss and clinically inapparent congenital cytomegalovirus infection (cCMV), as there is no consensus on treatment of this group. STUDY DESIGN: A nationwide, nonrandomized controlled trial, comparing 6 weeks of oral valganciclovir to no treatment in infants with cCMV, recruited after newborn hearing screening resulted in referral to an audiologist. The choice whether to treat was left to parents of subjects. Eligible subjects were full term infants aged <13 weeks with sensorineural hearing loss and diagnosed with cCMV through dried blood spot testing. The primary outcome, measured by linear and ordinal logistic regression, was change in best-ear hearing from baseline to follow-up at 18-22 months of age. RESULTS: Thirty-seven participants were included in the final analysis, of whom 25 were in the treatment group and 12 in the control group. The majority of subjects in both groups had neuroimaging abnormalities, which were mostly mild. Hearing deterioration was more likely in the control group compared with the treatment group (common OR 0.10, 95% CI 0.02-0.45, P = .003). Mean best-ear hearing deteriorated by 13.7 dB in the control group, compared with improvement of 3.3 dB in the treatment group (difference 17 dB, 95% CI 2.6 - 31.4, P = .02). CONCLUSIONS: We investigated treatment in children with hearing loss and clinically inapparent cCMV. Although our study was nonrandomized, it is the first prospective and controlled trial in this population. Valganciclovir-treated children with hearing loss and inapparent cCMV had less hearing deterioration at 18 through 22 months of age than control subjects. EUDRACT REGISTRY NUMBER: 2013-003068-30.

Gordon Holmes Syndrome Model Mice Exhibit Alterations in Microglia, Age, and Sex-Specific Disruptions in Cognitive and Proprioceptive Function.

Gordon Holmes syndrome (GHS) is a neurological disorder associated with neuroendocrine, cognitive, and motor impairments with corresponding neurodegeneration. Mutations in the E3 ubiquitin ligase RNF216 are strongly linked to GHS. Previous studies show that deletion of Rnf216 in mice led to sex-specific neuroendocrine dysfunction due to disruptions in the hypothalamic-pituitary-gonadal axis. To address RNF216 action in cognitive and motor functions, we tested Rnf216 knock-out (KO) mice in a battery of motor and learning tasks for a duration of 1 year. Although male and female KO mice did not demonstrate prominent motor phenotypes, KO females displayed abnormal limb clasping. KO mice also showed age-dependent strategy and associative learning impairments with sex-dependent alterations of microglia in the hippocampus and cortex. Additionally, KO males but not females had more negative resting membrane potentials in the CA1 hippocampus without any changes in miniature excitatory postsynaptic current (mEPSC) frequencies or amplitudes. Our findings show that constitutive deletion of Rnf216 alters microglia and neuronal excitability, which may provide insights into the etiology of sex-specific impairments in GHS.

Perigestational Opioid Exposure Alters Alcohol-Driven Reward Behaviors in Adolescent Rats.

Every fifteen minutes, a baby is born in the U.S. experiencing neonatal opioid withdrawal syndrome (NOWS). Since 2004, the rate of NOWS has increased 7-fold. Clinical studies have established intrauterine exposure to drugs of abuse as a risk factor for adverse health outcomes in adult life, including the propensity for future illicit drug use. Despite extensive knowledge about common mechanisms of action in the neural circuitry that drives opioid and alcohol reward, there is little data on the risks that those born with NOWS face regarding alcohol use later in life. Here, we investigate the impact of perigestational opioid exposure (POE) on the mesolimbic reward system of male and female Sprague Dawley rats at postnatal and adolescent ages. Our laboratory has developed a clinically relevant model for morphine exposure spanning pre-conception to the first week of life. Using this model, we found that POE increased alcohol consumption in female rats under noncontingent conditions, and inversely, reduced alcohol consumption in both male and female rats during operant conditioning sessions. Operant responding was also reduced for sucrose, suggesting that the impact of POE on reward-seeking behaviors is not limited to drugs of abuse. Expression of µ-opioid receptors was also significantly altered in the nucleus accumbens and medial habenula, regions previously shown to play a significant role in reward/aversion circuitry.

Increased LPS-Induced Fever and Sickness Behavior in Adult Male and Female Rats Perinatally Exposed to Morphine.

As a result of the current opioid crisis, the rate of children born exposed to opioids has skyrocketed. Later in life, these children have an increased risk for hospitalization and infection, raising concerns about potential immunocompromise, as is common with chronic opioid use. Opioids can act directly on immune cells or indirectly via the central nervous system to decrease immune system activity, leading to increased susceptibility, morbidity, and mortality to infection. However, it is currently unknown how perinatal opioid exposure (POE) alters immune function. Using a clinically relevant and translatable model of POE, we have investigated how baseline immune function and the reaction to an immune stimulator, lipopolysaccharide, is influenced by in utero opioid exposure in adult male and female rats. We report here that POE potentiates the febrile and neuroinflammatory response to lipopolysaccharide, likely as a consequence of suppressed immune function at baseline (including reduced antibody production). This suggests that POE increases susceptibility to infection by manipulating immune system development, consistent with the clinical literature. Investigation of the mechanisms whereby POE increases susceptibility to pathogens is critical for the development of potential interventions for immunosuppressed children exposed to opioids in utero.

Perinatal Morphine Exposure Induces Long-Term Changes in the Intestinal Microbiota of Male and Female Rats.

The increased use of opioids by women of reproductive age has resulted in a dramatic rise in number of infants exposed to opioids in utero. Although perinatal opioid exposure (POE) has been associated with an elevated risk of infection and hospitalization later in life, the mechanism(s) by which opioids influence immune development and maturation is not fully elucidated. Alterations in the intestinal microbiota composition, which leads to changes in immune training and maturation, could be at play. Chronic opioid use in adults is associated with a proinflammatory and pathogenic microbiota composition; therefore, we hypothesized here that in utero morphine exposure could negatively affect intestinal microbiota composition, leading to alterations in immune system function. We report that a clinically-relevant model of perinatal opioid exposure, in rats, induces profound intestinal microbiota dysbiosis that is maintained into adulthood. Furthermore, microbial maturity was reduced in morphine-exposed offspring. This suggests that increased risk of infection observed in children exposed to opioids during gestation may be a consequence of microbiota alterations with downstream impact on immune system development. Further investigation of how perinatal morphine induces dysbiosis will be critical to the development of early life interventions designed to ameliorate the increased risk of infection observed in these children.

Cardiac Remodeling in Subclinical Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial.

Importance: Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression. Objective: To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM. Design, Setting, and Participants: The multicenter, double-blind, placebo-controlled Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) randomized clinical trial was conducted from April 2014 to July 2019 at 17 sites in 4 countries (Brazil, Canada, Denmark, and the US), with 2 years of follow-up. The prespecified exploratory VANISH cohort studied here included sarcomere variant carriers with subclinical HCM and early phenotypic manifestations (reduced E' velocity, electrocardiographic abnormalities, or an increased left ventricular [LV] wall thickness [LVWT] to cavity diameter ratio) but no LV hypertrophy (LVH). Data were analyzed between March and December 2022. Interventions: Treatment with placebo or valsartan (80 mg/d for children weighing <35 kg, 160 mg/d for children weighing ≥35 kg, or 320 mg/d for adults aged ≥18 years). Main Outcomes and Measures: The primary outcome was a composite z score incorporating changes in 9 parameters of cardiac remodeling (LV cavity volume, LVWT, and LV mass; left atrial [LA] volume; E' velocity and S' velocity; and serum troponin and N-terminal prohormone of brain natriuretic peptide levels). Results: This study included 34 participants, with a mean (SD) age of 16 (5) years (all were White). A total of 18 participants (8 female [44%] and 10 male [56%]) were randomized to valsartan and 16 (9 female [56%] and 7 male [44%]) were randomized to placebo. No statistically significant effects of valsartan on cardiac remodeling were detected (mean change in composite z score compared with placebo: -0.01 [95% CI, -0.29 to 0.26]; P = .92). Overall, 2-year phenotypic progression was modest, with only a mild increase in LA volume detected (increased by 3.5 mL/m2 [95% CI, 1.4-6.0 mL/m2]; P = .002). Nine participants (26%) had increased LVWT, including 6 (18%) who developed clinically overt HCM. Baseline LA volume index (LAVI; 35 vs 28 mL/m2; P = .01) and average interventricular septum thickness (8.5 vs 7.0 mm; P = .009) were higher in participants who developed HCM. Conclusions and Relevance: In this exploratory cohort, valsartan was not proven to slow progression of subclinical HCM. Minimal changes in markers of cardiac remodeling were observed, although nearly one-fifth of patients developed clinically overt HCM. Transition to disease was associated with greater baseline interventricular septum thickness and LAVI. These findings highlight the importance of following sarcomere variant carriers longitudinally and the critical need to improve understanding of factors that drive disease penetrance and progression. Trial Registration: ClinicalTrials.gov Identifier: NCT01912534.

Calculation of ATP production rates using the Seahorse XF Analyzer.

Oxidative phosphorylation and glycolysis are the dominant ATP-generating pathways in mammalian metabolism. The balance between these two pathways is often shifted to execute cell-specific functions in response to stimuli that promote activation, proliferation, or differentiation. However, measurement of these metabolic switches has remained mostly qualitative, making it difficult to discriminate between healthy, physiological changes in energy transduction or compensatory responses due to metabolic dysfunction. We therefore present a broadly applicable method to calculate ATP production rates from oxidative phosphorylation and glycolysis using Seahorse XF Analyzer data and empirical conversion factors. We quantify the bioenergetic changes observed during macrophage polarization as well as cancer cell adaptation to in vitro culture conditions. Additionally, we detect substantive changes in ATP utilization upon neuronal depolarization and T cell receptor activation that are not evident from steady-state ATP measurements. This method generates a single readout that allows the direct comparison of ATP produced from oxidative phosphorylation and glycolysis in live cells. Additionally, the manuscript provides a framework for tailoring the calculations to specific cell systems or experimental conditions.

The HCM - Linked Mutation Arg92Leu in TNNT2 Allosterically Alters the cTnC - cTnI Interface and Disrupts the PKA-mediated Regulation of Myofilament Relaxation.

Background: Impaired left ventricular relaxation, high filling pressures, and dysregulation of Ca 2+ homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation in the sarcomere-gene-positive preclinical HCM cohort which suggests potential involvement of myofilament regulators of relaxation. Yet, a molecular level understanding of mechanism(s) at the level of the myofilament is lacking. We hypothesized that mutation-specific, allosterically mediated, changes to the cardiac troponin C-cardiac troponin I (cTnC-cTnI) interface can account for the development of early-onset diastolic dysfunction via decreased PKA accessibility to cTnI. Methods: HCM mutations R92L-cTnT (Arg92Leu) and Δ160E-cTnT (Glu160 deletion) were studied in vivo , in vitro, and in silico via 2D echocardiography, western blotting, ex vivo hemodynamics, stopped-flow kinetics, time resolved fluorescence resonance energy transfer (TR-FRET), and molecular dynamics simulations. Results: The HCM-causative mutations R92L-cTnT and Δ160E-cTnT result in different time-of-onset of diastolic dysfunction. R92L-cTnT demonstrated early-onset diastolic dysfunction accompanied by a localized decrease in phosphorylation of cTnI. Constitutive phosphorylation of cTnI (cTnI-D 23 D 24 ) was sufficient to recover diastolic function to Non-Tg levels only for R92L-cTnT. Mutation-specific changes in Ca 2+ dissociation rates associated with R92L-cTnT reconstituted with cTnI-D 23 D 24 led us to investigate potential involvement of structural changes in the cTnC-cTnI interface as an explanation for these observations. We probed the interface via TR-FRET revealing a repositioning of the N-terminus of cTnI, closer to cTnC, and concomitant decreases in distance distributions at sites flanking the PKA consensus sequence. Implementing TR-FRET distances as constraints into our atomistic model identified additional electrostatic interactions at the consensus sequence. Conclusion: These data indicate that the early diastolic dysfunction observed in a subset of HCM is likely attributable to structural changes at the cTnC-cTnI interface that impair accessibility of PKA thereby blunting ß-adrenergic responsiveness and identifying a potential molecular target for therapeutic intervention.

What Chicago community organizations needed to implement COVID-19 interventions: lessons learned in 2021.

Introduction: As the COVID-19 pandemic placed a spotlight on the health inequities in the United States, this study aimed to determine the local programmatic needs of community organizations (CO) delivering COVID-19 interventions across Chicago. Methods: In the summer of 2021, the Chicagoland CEAL Program interviewed 34 COs that were providing education, testing, and/or vaccinations in communities experiencing poor COVID-19 outcomes. The interviews were analyzed thematically and organized around logistical challenges and funding/resource needs. Results: The COs routinely offered testing (50%) or vaccinations (74%), with most (56%) employing some programmatic evaluation. Programs utilizing trusted-messenger systems were deemed most effective, but resource-intensive. CO specific needs clustered around sustaining effective outreach strategies, better CO coordination, wanting comprehensive trainings, improving program evaluation, and promoting services and programs. Conclusion: The COs reached populations with low-vaccine confidence using trusted messengers to overcome mistrust. However, replenishment of the resources needed to sustain such strategies should be prioritized. Leveraging the Chicagoland CEAL Program to help negotiate community organizations' interorganizational coordination, create training programs, and provide evaluation expertise are deliverable supports that may bolster COVID-19 prevention. Policy implications: Achieving health justice requires that all institutions of power participate in meaningful community engagement, help build community capacity, and infuse health equity throughout all aspects of the research and program evaluation processes.

Perinatal opioid exposure leads to decreased social play in adolescent male and female rats: Potential role of oxytocin signaling in brain regions associated with social reward.

Over the last two decades, the number of infants exposed to opioids in utero has quadrupled in the United States, with some states reporting rates as high as 55 infants per 1000 births. Clinical studies report that children previously exposed to opioids during gestation show significant deficits in social behavior, including an inability to form friendships or other social relationships. To date, the neural mechanisms whereby developmental opioid exposure disrupts social behavior remain unknown. Using a novel paradigm of perinatal opioid administration, we tested the hypothesis that chronic opioid exposure during critical developmental periods would disrupt juvenile play. As oxytocin is a major regulator of sociability, the impact of perinatal morphine exposure on oxytocin peptide expression was also examined. Juvenile play was assessed in vehicle- or morphine-exposed male and female rats at P25, P35, and P45. Classical features of juvenile play were measured, including time spent engaged in social play, time not in contact, number of pins, and number of nape attacks. We report that morphine-exposed males and females spend less time engaged in play behavior than control males and females, with a corresponding increase in time spent alone. Morphine-exposed males and females also initiated fewer pins and nape attacks. Together, these data suggest that male and female rats exposed to morphine during critical developmental periods are less motivated to participate in social play, potentially due to alterations in oxytocin-mediated reward signaling.

Perinatal Opioid Exposure Leads to Decreased Social Play in Adolescent Male and Female Rats: Potential Role of Oxytocin Signaling in Brain Regions Associated with Social Reward.

Over the last two decades, the number of infants exposed to opioids in utero has quadrupled in the United States, with some states reporting rates as high as 55 infants per 1000 births. Clinical studies report that children previously exposed to opioids during gestation show significant deficits in social behavior, including an inability to form friendships or other social relationships. To date, the neural mechanisms whereby developmental opioid exposure disrupts social behavior remain unknown. Using a novel paradigm of perinatal opioid administration, we tested the hypothesis that chronic opioid exposure during critical developmental periods would disrupt juvenile play. As oxytocin is a major regulator of sociability, the impact of perinatal morphine exposure on oxytocin peptide and receptor expression was also examined. Juvenile play was assessed in vehicle- or morphine-exposed male and female rats at P25, P35, and P45. Classical features of juvenile play were measured, including time spent engaged in social play, time not in contact, number of pins, and number of nape attacks. We report that morphine-exposed females spend less time engaged in play behavior than control males and females, with a corresponding increase in time spent alone. Morphine-exposed females also initiated fewer pins and nape attacks. Oxytocin receptor binding was reduced in morphine-exposed females in the nucleus accumbens, a brain region critical for social reward. Together, these data suggest that females exposed to morphine during critical developmental periods are less motivated to participate in social play, potentially due to alterations in oxytocin-mediated reward signaling.

The role of facility and patient mix factors on recovery of screening and diagnostic mammography volumes following the initial COVID-19 pandemic wave.

INTRODUCTION: The goal of this study was to understand the extent to which mammography facilities were able to recover monthly screening and diagnostic mammography volumes to their prepandemic levels and to determine what facility and patient mix factors were associated with recovery. METHOD: Facilities, located in and adjacent to Cook County, Illinois, were eligible. In all, 58 screening and 30 diagnostic mammogram facilities submitted mammogram volumes by month with a cross-listing of patient ZIP codes by screening volumes. Monthly screening and diagnostic volumes for the 6-month immediate postpandemic period (July-December 2020) and for the subsequent postpandemic period (January-June 2021) were compared with the same months in 2019. ZIP code distributions were used to define patient mix characteristics related to disadvantage. RESULTS: Compared with the prepandemic period, Breast Imaging Centers of Excellence conducted roughly 50 fewer monthly screening mammograms (95% CI: -91, -9) but 50 more diagnostic mammograms (95% CI: 24, 82) on average in the immediate postpandemic period. Facilities serving a predominantly Black population conducted roughly 50 fewer monthly screens (95% CI: -93, -13) without any increase in monthly diagnostics. CONCLUSION: Highly accredited (and typically higher volume) facilities appeared to actively triage diagnostics, whereas lower resource facilities appeared to struggle to recover to prepandemic volumes without triage to diagnostics. The pandemic disproportionally impacted minority populations already affected by differential access to and utilization of high-quality mammography. Potential explanations are discussed. Policies should be strengthened to facilitate triaging of services during times of stress to the healthcare system.

Identifying and Managing Nociplastic Pain in Individuals With Rheumatic Diseases: A Narrative Review.

Chronic pain is a burdensome and prevalent symptom in individuals with rheumatic disease. The International Association for the Study of Pain classifies pain into 3 descriptive categories: nociceptive, neuropathic, and nociplastic. These categories are intended to provide information about the mechanisms underlying the pain, which can then serve as targets for drug or non-drug treatments. This review describes the 3 types of pain as they relate to patients seen by rheumatology health care providers. The focus is on identifying individuals with nociplastic pain, which can either occur in isolation as in fibromyalgia, or as a comorbidity in individuals with primary autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythematosus. Practical information about how rheumatology health care providers can approach and manage chronic pain is also provided.