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Background: Kentucky is one of seven states with high, sustained rural HIV transmission tied to injection drug use. Expanding access to pre-exposure prophylaxis (PrEP) has been endorsed as a key HIV prevention strategy; however, uptake among people who inject drugs (PWID) has been negligible in rural areas. Syringe services programs (SSPs) have been implemented throughout Kentucky’s Appalachian region, providing an important opportunity to integrate PrEP services. Objectives: The primary objective was to examine preliminary efficacy and effect sizes of the study interventions on PrEP initiation among HIV-negative PWID. Design: Parallel group randomized controlled trial. Methods: Eighty participants were enrolled from two rural SSP locations in southeastern Kentucky. Following informed consent, participants completed a baseline interview, and were randomized to the intervention comparators. The primary endpoint was PrEP initiation, measured by dispensed PrEP prescription, within the 6-month study period. Analyses employed intent-to-treat (ITT) and per protocol approaches. Results: In total, 77/80 enrollees (96.2%) completed at least one session of their assigned intervention, regardless of trial arm. Seventy (87.5%) were linked to the embedded PrEP provider for the initial clinical visit; 38 (47.5%) completed a follow-up clinical visit with the provider, 22 (27.5%) were issued a prescription, and 7 (8.8%) initiated PrEP during the study period. We observed a 12.1% difference (14.6% vs 2.5%; ITT) and 12.8% difference (15.4% vs 2.6%; per protocol) in the primary outcome (PrEP initiation), in favor of the experimental intervention. Conclusion: This pilot trial established proof of concept for integrated PrEP care within SSPs in rural areas, and demonstrated a clinically meaningful difference in PrEP initiation between interventions, which warrants examination in a larger trial. Rates of early care discontinuation indicate a need for ongoing patient engagement strategies and implementation support for community SSPs. Trial registration: Prospective registration with ClinicalTrials.gov, NCT05037513 (registered August 5, 2021).

Abstract Background Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations. Methods This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12–25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant’s electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants’ perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.). Discussion This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA. ClinicalTrials.gov NCT06275191.

Summary: Background: Community stigma against people with opioid use disorder (OUD) and intervention stigma (e.g., toward naloxone) exacerbate the opioid overdose crisis. We examined the effects of the Communities that HEAL (CTH) intervention on perceived opioid-related community stigma by stakeholders in the HEALing Communities Study (HCS). Methods: We collected three surveys from community coalition members in 66 communities across four states participating in HCS. Communities were randomized into Intervention (Wave 1) or Wait-list Control (Wave 2) arms. We conducted multilevel linear mixed models to compare changes in primary outcomes of community stigma toward people treated for OUD, naloxone, and medication for opioid use disorder (MOUD) by arm from time 1 (before the start of the intervention) to time 3 (end of the intervention period in the Intervention arm). Findings: Intervention stakeholders reported a larger decrease in perceived community stigma toward people treated for OUD (adjusted mean change (AMC) −3.20 [95% C.I. −4.43, −1.98]) and toward MOUD (AMC −0.33 [95% C.I. −0.56, −0.09]) than stakeholders in Wait-list Control communities (AMC −0.18 [95% C.I. −1.38, 1.02], p = 0.0007 and AMC 0.11 [95% C.I. −0.09, 0.31], p = 0.0066). The relationship between intervention status and change in stigma toward MOUD was moderated by rural-urban status (urban AMC −0.59 [95% CI, −0.87, −0.32], rural AMC not sig.) and state. The difference in stigma toward naloxone between Intervention and Wait-list Control stakeholders was not statistically significant (p = 0.18). Interpretation: The CTH intervention decreased stakeholder perceptions of community stigma toward people treated for OUD and stigma toward MOUD. Implementing the CTH intervention in other communities could decrease OUD stigma across diverse settings nationally. Funding: US National Institute on Drug Abuse.

Background: Opioid overdoses differentially affect demographic groups. Strategies to reduce overdose deaths, specifically overdose education and naloxone distribution (OEND), are not consistently delivered equitably. Methods: The HEALing Communities StudySM (HCS) is a cluster-randomized trial designed to implement evidence-based practices, including OEND, to reduce overdose deaths across communities. Individuals receiving OEND in eight Kentucky counties between January 2020 and June 2022 provided demographics and overdose history. Recipient characteristics were compared to opioid overdose decedent characteristics to evaluate whether OEND was equitably delivered to the target population. Recipient characteristics were also analyzed based on whether OEND was delivered in criminal justice, behavioral health, or health care facilities. Results: A total of 26,273 demographic records were analyzed from 137 partner agencies. Most agencies were in behavioral health (85.6 %) or criminal justice sectors (10.4 %). About half of OEND recipients were male (50.6 %), which was significantly lower than the 70.3 % of overdose decedents who were male, (p

Abstract Background Stroke remains a major public health concern in the United States and a leading cause of long-term disability in adults. Dynamic body weight support (DBWS) systems are popular technology available for use in clinical settings such inpatient rehabilitation. However, there remains limited studies in such inpatient settings that compare DBWS to standard of care (SOC) using real world outcome measures. For survivors of acute ischemic stroke, we determine if incorporating a dynamic body weight support (DBWS) system into inpatient therapy offers greater improvement than standard of care (SOC). Methods A retrospective chart review included 52 individuals with an acute ischemic stroke admitted to an inpatient rehabilitation facility. Functional Independence Measure (FIM) data, specifically changes in FIM at discharge, served as the primary outcome measure. Patient cohorts received either therapies per SOC or therapies incorporating DBWS. Regardless of cohort group, all patients underwent therapies for 3 h per day for 5 days a week. Results For both groups, a statistically and clinically significant increase in total FIM (P

Summary: Background: Acquisition of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) are associated with negative health outcomes. Our adult intensive care unit (ICU) population has experienced low levels of CP-CRE acquisition; however, specific risk factors for this population at our medical facility have not been studied. Aims: To identify risk factors of CP-CRE acquisition and describe CP-CRE epidemiology among adult ICU patients at our medical facility. Methods: A retrospective cohort study was performed at a Kentucky Academic Medical Center. Surveillance specimens were collected at admission and weekly thereafter to identify CP-CRE colonization. Clinical data were extracted from patient medical records. Cases were defined as those who tested positive for CP-CRE on ICU admission day 3 or greater. Risk of CP-CRE acquisition was calculated using Modified Poisson regression. Findings: Independent risk factors of CP-CRE acquisition included administration of enteral tube feeds (risk ratio [RR], 4.46; 95% confidence interval [CI], 1.74–11.43); diagnosis of Clostridioides difficile enterocolitis (RR, 3.51; 95% CI, 1.27–9.68), pressure ulcer (RR, 3.48; 95% CI, 1.91–6.36), and morbid obesity (RR, 2.10; 95% CI, 1.12–3.95); having a drainage tube (RR, 2.63; 95% CI, 1.38–4.98); admission to a medical ICU (RR, 2.39; 95% CI, 1.32–4.35); 90-day use of a carbapenem (RR, 2.27; 95% CI, 1.21–4.26); and dialysis procedure (RR, 2.22; 95% CI, 1.15–4.27). Conclusion: Most CP-CRE risk factors were associated with alteration of colon microbiota and/or invasive procedures/devices. These results will assist in creating a more targeted CP-CRE active surveillance system and highlight areas for infection prevention intervention.

Abstract Background The HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) is a multi-site parallel group cluster randomized wait-list comparison trial designed to evaluate the effect of the Communities That Heal (CTH) intervention compared to usual care on opioid overdose deaths. Covariate-constrained randomization (CCR) was applied to balance the community-level baseline covariates in the HCS. The purpose of this paper is to evaluate the performance of model-based tests and permutation tests in the HCS setting. We conducted a simulation study to evaluate type I error rates and power for model-based and permutation tests for the multi-site HCS as well as for a subgroup analysis of a single state (Massachusetts). We also investigated whether the maximum degree of imbalance in the CCR design has an impact on the performance of the tests. Methods The primary outcome, the number of opioid overdose deaths, is count data assessed at the community level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the type I error rates and power for 3 tests: (1) Wald-type t-test with small-sample corrected empirical standard error estimates, (2) Wald-type z-test with model-based standard error estimates, and (3) permutation test with test statistics calculated by the difference in average residuals for the two groups. Results Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved type I error rates if the constrained space was not too small. For all tests, the power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA). Conclusions Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study. Trial registration ClinicalTrials.gov http://www.clinicaltrials.gov ; Identifier: NCT04111939

Neonatal abstinence syndrome (NAS) presents with a varying severity of withdrawal signs and length of treatment (LOT). We examined the course and relevance of each of the NAS withdrawal signs during treatment in a sample of 182 infants with any prenatal opioid exposure, gestational age ≥ 35 weeks, without other medical conditions, and meeting the criteria for pharmacological treatment. Infants were monitored using the Finnegan Neonatal Abstinence Scoring Tool. Daily mean Finnegan scores were estimated using linear mixed models with random subject effects to account for repeated withdrawal scores from the same subject. Daily item prevalence was estimated using generalized estimating equations with a within-subject exchangeable correlation structure. The median LOT was 12.86 days. The prevalence of withdrawal signs decreased from day one to day three of treatment. However, certain central nervous system (CNS) and gastrointestinal (GI) signs showed sporadic increases in prevalence notable around two weeks of treatment, accounting for increases in Finnegan scores that guided pharmacotherapy. We question whether the resurgence of signs with a prolonged LOT is mainly a consequence of opioid tolerance or withdrawal. Monitoring CNS and GI signs throughout treatment is crucial. Future studies directed to better understand this clinical phenomenon may lead to the refining of NAS pharmacotherapy and perhaps the discovery of treatment alternatives.

Abstract Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the effects on CD86/CD68 macrophages were inconsistent between lean and obese. However, linear regression analysis did not find significant relationships between the change in macrophage numbers and the change in UCP1 protein abundance. A high percentage of CD163 macrophages in SC WAT expressed UCP1, and these UCP1 expressing CD163 macrophages were significantly increased by cold treatment in SC WAT of lean subjects. In conclusion, our results suggest that CD163 macrophages are involved in some aspect of the tissue remodeling that occurs during SC WAT beiging in humans after cold treatment, but they are likely not direct mediators of the beiging process.

Abstract Background The aim of this study was to examine whether cultural factors, such as religiosity and social support, mediate/moderate the relationship between personal/psychosocial factors and T2DM self-care in a rural Appalachian community. Methods Regression models were utilized to assess for mediation and moderation. Multilevel linear mixed effects models and GEE-type logistic regression models were fit for continuous (social support, self-care) and binary (religiosity) outcomes, respectively. Results The results indicated that cultural context factors (religiosity and social support) can mediate/moderate the relationship between psychosocial factors and T2DM self-care. Specifically, after adjusting for demographic variables, the findings suggested that social support may moderate the effect of depressive symptoms and stress on self-care. Religiosity may moderate the effect of distress on self-care, and empowerment was a predictor of self-care but was not mediated/moderated by the assessed cultural context factors. When considering health status, religiosity was a moderately significant predictor of self-care and may mediate the relationship between perceived health status and T2DM self-care. Conclusions This study represents the first known research to examine cultural assets and diabetes self-care practices among a community-based sample of Appalachian adults. We echo calls to increase the evidence on social support and religiosity and other contextual factors among this highly affected population. Trial registration US National Library of Science identifier NCT03474731. Registered March 23, 2018, www.clinicaltrials.gov .

Neonatal abstinence syndrome (NAS) refers to cadre of withdrawal manifestations in infants born to mothers who used illicit and licit substances during pregnancy. The increasing prevalence of NAS has been largely due to the maternal use of opioids during pregnancy. NAS contributes to increased morbidity and long-term disability in surviving infants. Clinically, oral opioid therapies for opioid exposure have been a standard treatment with morphine (MO) being the most commonly used medication. Recently, a non-opioid agent, clonidine (CD) has also been used with potentially favorable short- and long-term outcomes in infants. However, data regarding the cellular and molecular effects of these treatments on the developing brain is still lacking due to a lack of a reliable animal model that targets the neonatal brain. To address this gap in knowledge we determined the effects of MO or CD on the cell death of neonatal cortical explant cultures that were exposed to oxycodone (OXY) in utero. Sprague Dawley rats were randomized and implanted with programmable infusion pumps before mating to receive either the OXY (dose increasing from 1.21–1.90 mg/kg/day to a maximum dose of 2.86–3.49 mg/kg/day) or normal saline (NS) throughout pregnancy and until one week after delivery. Male and female rat pups were sacrificed on postnatal day 4, and the prefrontal cortex (PFC) and hippocampus (HC) were dissected and treated with MO (0.10–1.00 µM) or CD (1.20–120.00 µM) in culture media. After 5 days of treatment the explants were labeled with propidium iodide to detect cell death. Dead cells were analyzed and counted under fluorescence microscopy. In explants from the PFC, cell death was greater in those prenatally exposed to OXY and postnatally treated with MO (OXY/MO) (736.8 ± 76.5) compared to OXY/CD (620.9 ± 75.0; p = 0.005). In the HC explants, mean cell death counts were not significantly different between groups regardless of prenatal exposure or postnatal treatment (p = 0.19). The PFC is vital in controlling higher-order executive functions such as behavioral flexibility, learning and working memory. Therefore, our finding is consistent with executive function problems in children with prenatal opioid exposure.

Abstract Background Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients. Methods Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as the trans-diaphragmatic pressure generated by supramaximal magnetic phrenic nerve stimulation (PdiTw). Quadriceps strength was assessed as leg force generated by supramaximal magnetic femoral nerve stimulation (QuadTw). Diaphragm and quadriceps thickness were assessed by ultrasound. Baseline measurements of muscle strength and size were performed, and patients were then randomized to one of four treatment groups (placebo, HMB 3 gm/day, EPA 2 gm/day and HMB plus EPA). Strength and size measurements were repeated 11 days after study entry. ANCOVA statistical testing was used to compare variables across the four experimental groups. Results Treatments failed to increase the strength and thickness of either the diaphragm or quadriceps when compared to placebo. In addition, treatments also failed to decrease the duration of mechanical ventilation after study entry. Conclusions These results indicate that a 10-day course of HMB and/or EPA does not improve skeletal muscle strength in critically ill mechanically ventilated patients. These findings also confirm previous reports that diaphragm and leg strength in these patients are profoundly low. Additional studies will be needed to examine the effects of other anabolic agents and innovative forms of physical therapy. Trial registration: ClinicalTrials.gov, NCT01270516. Registered 5 January 2011, https://clinicaltrials.gov/ct2/show/NCT01270516?term=Supinski&draw=2&rank=4 .

# Background Preseason movement screening can identify modifiable risk factors, deterioration of function, and potential for injury in baseball players. Limited resources and time intensive testing procedures prevent high school coaches from accurately performing frequent movement screens on their players. # Purpose To establish the intra-rater and inter-rater reliability of a novel arm care screening tool based on the concepts of the Functional Movement Screen (FMS™) and Selective Functional Movement Assessment (SFMA™) in high school coaches. # Study Design Methodological intra- and inter-rater reliability study # Methods Thirty-one male high school baseball players (15.9 years ± 1.06) were independently scored on the Arm Care Screen (ACS) by three examiners (two coaches, one physical therapist) in real-time and again seven days later by reviewing video recordings of each players’ initial screening performance. Results from each examiner were compared within and between raters using Cohen’s kappa and percent absolute agreement. # Results Substantial to excellent intra-rater and inter-rater reliability were established among all raters for each component of the ACS. The mean Cohen’s kappa coefficient for intra-rater reliability was 0.76 (95% confidence interval, 0.54-0.95) and percent absolute agreement ranged from 0.82-0.94 among all raters. Inter-rater reliability demonstrated a mean Cohen’s kappa value of 0.89 (95% confidence interval, 0.77-0.99) while percent absolute agreement between raters ranged from 0.81-1.00. Intra- and inter-rater reliability did not differ between raters with various movement screening experience (p>0.05). # Conclusions High school baseball coaches with limited experience screening movement can reliably score all three components of the ACS in less than three minutes with minimal training. # Level of Evidence Level 3, Reliability study

Purpose: Cluster randomized controlled trials (cRCTs) are popular in school-based research designs where schools are randomized to different trial arms. To help guide future study planning, we provide information on anticipated effect sizes and intra-cluster correlation coefficients (ICCs), as well as school sizes, for dating violence (DV) and interpersonal violence outcomes based on data from a cRCT which evaluated the bystander-based violence intervention ‘Green Dot’. Methods: We utilized data from 25 schools from the Green Dot High School study. Effect size and ICC values corresponding to dating and interpersonal violence outcomes are obtained from linear mixed effect models. We also calculated the required number of schools needed for future studies utilizing available methods that do and do not consider variation in school size. Results: Observed effect sizes for DV outcomes range from 0.06 to 0.11. Observed ICC values for DV outcomes range from 0.0006 to 0.0032. The upper limit of 95% CIs for the true ICCs range from 0.0023 to 0.0070. Conclusion: School-based evaluations with violence outcomes are expected to have small effect sizes. Observed ICCs are less than 0.005 and upper limit of of 95% CIs for the true ICCs are less than 0.01. Designing school-based cRCTs should account for the ICC, even if its value is assumed to be negligible. Furthermore, variation in school sizes should also be accounted for to avoid having too few schools to achieve the desired power.

BACKGROUND Beige and brown adipose tissue (BAT) are associated with improved metabolic homeostasis. We recently reported that the β3-adrenergic receptor agonist mirabegron induced beige adipose tissue in obese insulin-resistant subjects, and this was accompanied by improved glucose metabolism. Here we evaluated pioglitazone treatment with a combination pioglitazone and mirabegron treatment and compared these with previously published data evaluating mirabegron treatment alone. Both drugs were used at FDA-approved dosages.METHODS We measured BAT by PET CT scans, measured beige adipose tissue by immunohistochemistry, and comprehensively characterized glucose and lipid homeostasis and insulin sensitivity by euglycemic clamp and oral glucose tolerance tests. Subcutaneous white adipose tissue, muscle fiber type composition and capillary density, lipotoxicity, and systemic inflammation were evaluated by immunohistochemistry, gene expression profiling, mass spectroscopy, and ELISAs.RESULTS Treatment with pioglitazone or the combination of pioglitazone and mirabegron increased beige adipose tissue protein marker expression and improved insulin sensitivity and glucose homeostasis, but neither treatment induced BAT in these obese subjects. When the magnitude of the responses to the treatments was evaluated, mirabegron was found to be the most effective at inducing beige adipose tissue. Although monotherapy with either mirabegron or pioglitazone induced adipose beiging, combination treatment resulted in less beiging than either alone. The 3 treatments also had different effects on muscle fiber type switching and capillary density.CONCLUSION The addition of pioglitazone to mirabegron treatment does not enhance beiging or increase BAT in obese insulin-resistant research participants.TRIAL REGISTRATION ClinicalTrials.gov NCT02919176.FUNDING NIH DK112282 and P20GM103527 and Clinical and Translational Science Awards grant UL1TR001998.

Objective: To better understand the role of the presence or absence of motor-evoked potentials (MEPs) in predicting functional outcomes following a severe-moderate stroke. Design: Retrospective exploratory analysis. We compared the effects of the stimulation condition (active or sham), MEP status (+ or −), and a combination of stimulation condition and MEP status on outcome. Within-group and between-group changes were assessed with longitudinal repeated measures analysis of variance and longitudinal repeated measures analysis of covariance, respectively. The proportions of participants who achieved minimal clinically important differences (MCIDs) for the main outcome measures were calculated. Setting: University research laboratory within a rehabilitation hospital. Participants: A total of 129 subjects with severe-moderate stroke-related motor impairments who participated in previous studies combining neuromodulation and motor training Interventions: Neuromodulation (active or sham) and motor training. Main Outcome Measures: Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT). Results: When participants were grouped by stimulation condition or MEP status, all groups improved from baseline to immediate postintervention and follow-up evaluations (all P.05). Regarding MCIDs, in the MEP−/active group, 14.5% of individuals reached MCID on FMA and 8.3% on ARAT post intervention. In the MEP+/active group, 33.3% of individuals reached MCID on FMA and 27.3% on ARAT post intervention. Conclusion: As expected, the MEP+ group had the greatest improvement in motor function. However, it was shown that individuals without MEPs can also achieve meaningful changes, as reflected by MCID, when neuromodulation is paired with motor training. To our knowledge, this is the first study to differentiate the effects of neuromodulation by MEP status. Keywords: Rehabilitation, Transcranial direct current stimulation, Transcranial magnetic stimulation

Objective: To determine whether chronicity influences outcomes of somatosensory stimulation paired with task-oriented motor training for participants with severe-to-moderate upper extremity hemiparesis. Design: Spearman correlations were used to retrospectively analyze outcomes of a randomized trial. Setting: University research laboratory at a rehabilitation hospital. Participants: Adults, ranging between 3 and 12 months poststroke (N=55). Interventions: About 18 sessions pairing either 2 hours of active (n=33) or sham (n=22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. Main Outcome Measures: The Wolf Motor Function Test (primary), Action Research Arm Test, Stroke Impact Scale, and Fugl-Meyer Assessment were collected as outcome measures. Analyses evaluated whether within-group chronicity correlated with pre-post changes on primary and secondary outcome measures of motor performance. Results: Both groups exhibited improvements on all outcome measures. No significant correlations between chronicity poststroke and the amount of motor recovery were found. Conclusion: Somatosensory stimulation improved motor recovery compared with sham treatment in cases of severe-to-moderate hemiparesis between 3 and 12 months poststroke; and the extent of recovery did not correlate with baseline levels of stroke chronicity. Future studies should investigate a wider period of inclusion, patterns of corticospinal reorganization, differences between cortical and subcortical strokes, and include long-term follow-up periods. Keywords: Humans, Occupational therapy, Rehabilitation, Transcutaneous electric nerve stimulation, Upper extremity

Obesity results in greater aortic stiffness assessed by carotid-femoral Pulse Wave Velocity (cfPWV), which is an independent predictor of cardiovascular (CV) events. We hypothesized that a novel curcumin formulation with enhanced bioavailability, CurQfen®, would reduce cfPWV and inflammation in young, obese men. In the present placebo-controlled pilot study, 22 obese subjects (BMI ⩾ 30.0 kg/m2) were randomized into placebo (n = 11, BMI = 33.18 ± 3.38 kg/m2) and curcumin (n = 11, BMI = 33.29 ± 3.69 kg/m2) supplemented groups. When CurQfen® was supplemented at 500 mg/day for 12 weeks, it was found that individuals who did respond to the treatment (n = 6) entered the study with higher baseline cfPWV versus those who did not respond (n = 5) (6.81 ± 0.83 m/s v. 5.84 ± 0.41 m/s, p = 0.045, group by time interaction). The curcumin responders also had increased plasma IL-13 concentrations (p = 0.018, 12 weeks v. baseline). These findings suggest CurQfen curcumin has potential to de-stiffen arteries in young, obese men with greater aortic stiffness.

Preterm infants with respiratory distress may require mechanical ventilation which is associated with increased pulmonary morbidities. Prompt and successful extubation to noninvasive support is a pressing goal. In this communication, we show original data that increased recurring intermittent hypoxemia (IH, oxygen saturation

Objectives: To compare the Shennan's and the consensus definition of Bronchopulmonary Dysplasia (BPD) from the National Institutes of Health (NIH) workshop and analyze specific risk factors associated with each definition.Study design: Retrospective analysis of records of 274 infants admitted to a level IV intensive care unit. Infants were classified as having BPD or no BPD by both definitions. Differences in incidence and risk factors were analyzed. Statistical methods included descriptive statistics, comparative tests, and marginal logistic regression modeling.Results: The estimated difference in prevalence was 32% [95% CI: (26%, 37%), (p < 0.0001)] between both criteria. The prevalence of BPD was 80% higher based on the NIH criteria [RR = 1.80; 95% CI: (1.58, 2.06)]. Infants with no BPD by the Shennan definition were breathing room air with or without positive or continuous pressure support and were most likely to be discharged home on oxygen [OR = 4.47, 95% CI: (1.20, 16.61), p = 0.03]. Gestational age, birth weight, and 1-min Apgar score predicted BPD by both definitions. Chorioamnionitis increased the risk of BPD by the Shennan definition but was associated with lower risk by the NIH criteria. IUGR was associated with BPD by the Shennan definition and with severe BPD by the NIH criteria.Conclusion: Compared to the Shennan's definition, the NIH consensus identified 80% more infants with BPD and is a better predictor of oxygen requirement at discharge. Until a new better criteria is develop, the NIH consensus definition should be used across centers.

IntroductionIntermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure and IH in preterm infants.MethodsIn order to accurately calculate IH, SpO2 data were prospectively collected using high-resolution pulse oximeters during the first 8 weeks of life in preterm infants less than 30 weeks gestational age. Data related to prenatal opioid misuse were retrospectively collected from medical charts. Infants with tobacco or poly-drug exposure were excluded. The primary outcome measure is percent time spent with SpO2 below 80% (%time-SpO2

BackgroundBrain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS.ObjectiveTo compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS.MethodsThis is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS.Results67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045).ConclusionPlasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure.

In the face of the current Neonatal Abstinence Syndrome (NAS) epidemic, there is considerable variability in the assessment and management of infants with NAS. In this manuscript, we particularly focus on NAS assessment, with special attention given to the popular Finnegan Neonatal Abstinence Score (FNAS). A major instigator of the problem of variable practices is that multiple modified versions of the FNAS exist and continue to be proposed, including shortened versions. Furthermore, the validity of such assessment tools has been questioned, and as a result, the need for better tools has been suggested. The ultimate purpose of this manuscript, therefore, is to increase researchers’ and clinicians’ understanding on how to judge the usefulness of NAS assessment tools in order to guide future tool development and to reduce variable practices. In short, we suggest that judgment of NAS assessment tools should be made on a clinimetrics viewpoint as opposed to psychometrically. We provide examples, address multiple issues that must be considered, and discuss future tool development. Furthermore, we urge researchers and clinicians to come together, utilizing their knowledge and experience, to assess the utility and practicality of existing assessment tools and to determine if one or more new or modified tools are needed with the goal of increased agreement on the assessment of NAS in practice.

ObjectiveIn a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, a novel isohumulone drug, increased total and high-molecular weight (HMW) adiponectin in plasma. The objective was to determine whether KDT501 increased adiponectin secretion from subcutaneous white adipose tissue (SC WAT) and the underlying mechanism(s).MethodsNine obese participants with either prediabetes or with normal glucose tolerance plus three features of metabolic syndrome were part of the study. SC WAT biopsies were performed before and after 28 days of KDT501 treatment in a clinical research setting. In addition, a cold stimulus was used to induce thermogenic gene expression. Adiponectin secretion was measured, and gene expression of 130 genes involved in adipose tissue function was determined. The effect of KDT501 on adipocyte mitochondrial function was analyzed in vitro.ResultsSC WAT explants secreted more total and HMW adiponectin after KDT501 treatment (P

Opiate addiction is now a major public health problem. Perinatal insults and exposure to opiates such as morphine in utero are well known to affect development of the hypothalamic–pituitary–adrenal axis of the offspring adversely and are associated with a higher risk of developing neurobehavioral problems. Oxycodone is now one of the most frequently abused pain killers during pregnancy; however, limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters neurobehavioral outcomes of the offspring. We demonstrated that exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant effects of POE were detected on isolation-induced ultrasonic vocalizations in the early postnatal period or on learning and memory in the water maze in adult offspring. Our findings are consistent with hyperactivity problems identified in children exposed to opiates in utero.

BackgroundThe HEALing Communities Study (HCS) included health campaigns as part of a community-engaged intervention to reduce opioid-related overdose deaths in 67 highly impacted communities across Kentucky, Massachusetts, New York, and Ohio. Five campaigns were developed with community input to provide information on opioid use disorder (OUD) and overdose prevention, reduce stigma, and build demand for evidence-based practices (EBPs). An evaluation examined the recognition of campaign messages about naloxone and whether stigma and efficacy beliefs regarding OUD treatment and naloxone changed in HCS intervention communities.MethodsData were collected through surveys offered on Facebook/Instagram to members of communities participating in the HCS intervention and wait-list control communities.ResultsParticipants in HCS intervention communities reported a reduction in stigma regarding OUD and increased efficacy beliefs regarding naloxone associated with recognition of campaign messages. However, this finding is cautiously interpreted as there was no clear evidence for recognition differences between the treatment/control conditions.ConclusionStudy findings indicate associations between campaign message recognition and positive outcomes. Results also highlight possible challenges concerning evaluations of social media campaigns using conventional evaluation techniques.Trial registrationClinicalTrials.gov NCT04111939.