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No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; EXP 2) mg/day pregabalin in cannabis users who were not seeking treatment or trying to reduce/quit their cannabis use. The protocol consisted of two outpatient maintenance phases (11 days in EXP 1 and 15 days in EXP 2) that concluded with four experimental sessions within each phase. During experimental sessions, maintenance continued, and participants completed two 2-day blocks of sampling and self-administration sessions to determine the reinforcing effects of smoked cannabis (0% and 5.9% delta⁹-tetrahydrocannabinol [THC]), as well as subjective, attentional bias, performance, and physiological responses. In addition, naturalistic cannabis use, side effects, sleep quality, craving, and other self-reported substance use were measured during pregabalin maintenance. Cannabis was self-administered and produced prototypical effects, but pregabalin generally did not impact the effects of cannabis or alter naturalistic use. These human laboratory results in cannabis users not trying to reduce/quit their use do not support the efficacy of pregabalin as a stand-alone pharmacotherapy for CUD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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

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 The purpose of this study was to identify differences related to race in preoperative and intraoperative findings of patients undergoing operative treatment for shoulder instability. Methods Data from the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort were used. Of 1010 patients, 995 provided race and ethnicity information and were included in the analyses. Demographic characteristics, injury history, radiographic and intraoperative findings, and preoperative patient-reported instability, pain, and function were compared (1) between white and minority patients and (2) in a subgroup analysis between white patients and the 3 largest minority groups. The Distressed Communities Index (DCI) score was recorded for each patient’s home ZIP code. Multiple logistic regressions were performed to determine whether models consisting of race/ethnicity, insurance carrier, and/or DCI score were predictive of bone and cartilage loss at the time of surgery. Results Compared with white patients, a greater percentage of US minority patients had ≥2 dislocations (68.0% vs. 57.1%, P = .01), which corresponded with more frequent articular cartilage lesions (62.2% vs. 51.0%, P = .007) and increased frequencies of glenoid bone loss > 10% (16.2% vs. 8.7%, P = .03) and Hill-Sachs lesions (68.6% vs. 56.0%, P = .004). Specifically, when compared with white patients, African American and Asian patients showed significantly increased frequencies of glenoid bone loss > 10% (19.7% of African American patients, 18.4% of Asian patients, and 8.9% of white patients; P = .01) and Hill-Sachs lesions (65.6%, 71.7%, and 52.4%, respectively; P = .02). Race was an independent predictor of articular cartilage lesions (P = .04) and the presence of Hill-Sachs lesions (P = .01). A higher DCI score (P = .03) and race (P = .04) were both predictive of having glenoid bone loss > 10%. Conclusion We found that minority race was associated with increased number of preoperative dislocations and increased frequency of articular cartilage and Hill-Sachs lesions at the time of surgery, and both minority race and an increased DCI score were associated with glenoid bone loss > 10%. Further research is needed to understand the underlying reason for these differences and to optimize care for all patients with shoulder instability.

Context: Awareness of important injury risk factors associated with excessive pitching volume has been highlighted in the literature, but injury rates remain high. Shoulder pain in baseball players is associated with various changes in musculoskeletal movements, which presents as measurable impairments throughout the kinetic chain. Baseball coaches and rehabilitation professionals have utilized exercise programs targeting strength and flexibility of the throwing arm to prevent injuries. The purpose of this review is to summarize the current evidence regarding the effectiveness of arm care exercise programs in reducing upper extremity injury rates in adolescent baseball players. Evidence Acquisition: A search of electronic databases, including CINAHL with full text, MEDLINE, and SPORTDiscus was conducted to retrieve available articles in English from the years 2010 through 2020. The search terms injury prevention, exercise, and adolescent baseball were used. Study Design: Clinical review. Level of Evidence: Level 4. Results: Improving shoulder internal rotation range of motion by stretching the posterior shoulder muscles daily was associated with a 36% risk reduction of shoulder and elbow injuries. Group-based arm care exercise programs that target multiple musculoskeletal impairments demonstrated an approximately 50% reduced risk of elbow injury. Conclusion: For adolescent baseball players, arm care injury prevention programs focusing on important musculoskeletal impairments are effective at reducing injury incidence rates. Multimodal injury prevention programs that improve multiple musculoskeletal impairments are more comprehensive and may result in better injury reduction than programs focusing on a singular impairment.

The purpose of this study was to compare postural control and neurophysiologic components of balance after dry needling of the fibularis longus between individuals with chronic ankle instability (CAI) and a healthy control group.This quasi-experimental university-laboratory study included 50 adult volunteers-25 with CAI (16 female, 9 male; age: 26 ± 9.42 years; height: 173.12 ± 9.85 cm; weight: 79.27 ± 18 kg) and 25 healthy controls (15 female, 10 male; age: 25.8 ± 5.45 years; height: 169.47 ± 9.43 cm; weight: 68.47 ± 13 kg). Participants completed the Star Excursion Balance Test (SEBT), single-leg balance, and assessment of spinal reflex excitability before and after a single treatment of dry needling to the fibularis longus. The anterior, posterolateral, and posteromedial directions of the SEBT were randomized, and reach distances were normalized to a percentage of leg length. A composite SEBT score was calculated by averaging the normalized scores. Postural control was assessed in single-limb stance on a force plate through time-to-boundary measurements in eyes-open and eyes-closed conditions. Fibularis longus and soleus spinal reflexes were obtained by providing electrical stimulation to the common fibular and tibial nerves with participants lying prone. A Group × Time analysis examined changes in performance, and effect sizes were calculated to assess significance.Significant group × time interactions were identified for composite (P = .006) and posteromedial (P = .017) SEBT scores. Significant time effects for all directions of the SEBT, time to boundary with eyes open, and the mediolateral direction with eyes closed indicate improved postural control following treatment (P.008). Within-group effect sizes for significant time effects ranged from small to large, indicating potential clinical utility.Dry needling demonstrated immediate short-term improvement in measures of static and postural control in individuals with CAI as well as healthy controls.

BACKGROUNDBeige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.METHODSBefore and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle.RESULTSThe clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and β cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in β cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSIONMirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal muscle do not express β3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves β cell function.TRIAL REGISTRATIONClinicaltrials.gov NCT02919176.FUNDINGNIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998.

Rehabilitation strategies after traumatic spinal cord injury aim to maximize functional recovery by applying principles of neuroplasticity via task-specific, repetitive training. Rehabilitation of patients with traumatic spinal cord injury poses unique challenges, including bilateral limb involvement, autonomic dysfunction, loss of proprioception, and potentially spinal precautions/bracing. The purpose of this retrospective case series was to determine whether use of dynamic body weight support would yield greater improvement in functional recovery compared with standard of care in adults with traumatic spinal cord injury. Data were collected from patients with traumatic spinal cord injury who completed inpatient rehabilitation incorporating dynamic body weight support (n = 5) and who completed inpatient rehabilitation without dynamic body weight support (n = 5). The primary outcome measure was the change in Functional Independence Measures. The dynamic body weight support group had a significantly greater improvement in Total Functional Independence Measures and in Functional Independence Measures motor subscale compared with the standard of care group (P = 0.023 and P = 0.033, respectively). This study presents initial evidence that dynamic body weight support therapy during inpatient rehabilitation has the potential to improve functional independence compared with standard of care in patients with traumatic spinal cord injury. Larger prospective randomized studies need to be conducted to expand on these findings.

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.

Critically ill mechanically ventilated (MV) patients develop significant muscle weakness, which has major clinical consequences. There remains uncertainty, however, regarding the severity of leg weakness, the precise relationship between muscle strength and thickness, and the risk factors for weakness in MV patients. We therefore measured both diaphragm (PdiTw) and quadriceps (QuadTw) strength in MV patients using magnetic stimulation and compared strength to muscle thickness. Both PdiTw and QuadTw were profoundly reduced for MV patients, with PdiTw 19 % of normal and QuadTw 6% of normal values. There was a poor correlation between strength and thickness for both muscles, with thickness often remaining in the normal range when strength was severely reduced. Regression analysis revealed reductions in PdiTw correlated with presence of infection (p = 0.006) and age (p = 0.007). QuadTw best correlated with duration of MV (p = 0.036). Limb muscles are profoundly weak in critically ill patients, with a severity that mirrors the level of weakness observed in the diaphragm.

Objective The objective of the study was to determine the clinical utility of brain natriuretic peptide (NT-proBNP) for prediction of moderate to severe bronchopulmonary dysplasia (BPD). We hypothesized that elevated NT-proBNP levels at 4 weeks of postnatal age may predict the severity of BPD in preterm infants. Study design The study design was a prospective observational study. The research team enrolled and followed a cohort of 70 infants with gestational age less than or equal to 30 weeks. The plasma NT-proBNP levels were measured at the postnatal day 28th. We further followed and categorized infants into two groups. Infants with no or mild BPD (Group 1) and infants with moderate or severe BPD (Group 2). We compared plasma NT-proBNP levels at 28th day of postnatal life between Groups 1 and 2. The difference in NT-proBNP levels on day 28th between groups was used to predict the severity of BPD. Results Plasma NT-proBNP was significantly elevated in Group 2 compared with Group 1, median (IQR) of 845 pg/mL (553, 1632) compared with 726 pg/mL (391, 923), P = 0.02. NT-proBNP had a fair predictive accuracy (C statistics of 0.68) to determine moderate to severe BPD. Conclusion NT-proBNP may be a useful biomarker in conjunction with clinical factors as a predictor of severe BPD. For future directions, the trend of NT-proBNP in infants with BPD may have clinical significance in monitoring of the disease.

Background Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments. Objective To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI. Methods Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = 6) and who received inpatient rehabilitation without DBWS (SOC, n = 6). The primary outcome measure was the change in Functional Independence Measures (FIM) scores from admission to discharge. Results There was significant improvement in total FIM scores at discharge compared to admission for both the DBWS (p = 0.001) and SOC (p = 0.005) groups. Overall, the DBWS group had greater improvement in total FIM score and FIM subscales compared to the SOC group. Conclusions Our results suggest DBWS has the potential to allow a greater intensity of therapy during inpatient rehabilitation and yield better outcomes compared to SOC in patients with TBI.

OBJECTIVES Analyze risk factors affecting length of stay (LOS) for patients presenting with deep neck space infections including care by medical versus surgical team. METHODS This is a retrospective chart review from January 2005 through May 2018 at the University of Kentucky analyzing factors related to deep neck space abscesses. Patients included adults >18 years old admitted for deep neck space infections undergoing surgical intervention. This study compared effects of treatment on a medical versus surgical service on LOS while accounting for patient confounders. Independent variables included age, gender, tobacco use, medical comorbidities, Charlson comorbidity index, American Society of Anesthesiology (ASA) classification, presence of drain, readmissions, and repeat surgical interventions. Univariate and multivariate analysis were performed. RESULTS One hundred sixty-three patients were included in the analysis. LOS was significantly longer for those on medicine services (P

Objective The relationship between hearing loss and cognitive decline is of great importance with growing evidence of hearing loss as an independent modifiable risk factor for dementia. Our goal was to evaluate for differences in dementia neuropathology between subjective normal hearing and hearing loss subjects, as well as subjects who wore hearing aids. Study design Retrospective database. Setting Tertiary academic center. Patients Brain tissue analyzed from our Center on Aging. Demographics, subjective hearing status, hearing aid use, cognitive status, and dementia neuropathology documented. Interventions Dementia neuropathology analyzed in brains of normal hearing and hearing loss subjects. Main outcome measures Differences in dementia neuropathology between hearing groups. Groups were compared using logistic regression and analysis of covariance (ANCOVA). Results Two-hundred and seventy-three subjects were included, 189 normal hearing and 84 subjective hearing loss subjects. No significant difference demonstrated in Alzheimer's disease neuropathology (p > 0.05) or pathologic stage (p = 0.2471). No significant difference observed in neuropathology of other major dementia types, specifically, presence of Lewy bodies (p > 0.05), Lewy body disease pathologic stage (p = 0.9778), or presence of micro-infarcts, macro-infarcts, or arteriosclerosis (p > 0.05). Hearing aid-wearing subjects had a lower prevalence of clinical dementia (39.1% versus 57.9%; p = 0.0208) with no significant difference in dementia neuropathology (p > 0.05). Conclusion Subjective hearing loss was not found to be associated with significantly different dementia neuropathology, which counters hypotheses on hearing loss causing permanent neurodegeneration and cognitive decline. Hearing aid users were found to have a lower prevalence of dementia for similar levels of neurodegeneration, suggesting a potential neuroprotective effect of hearing aids.

Context The gut microbiome is a source of inflammatory factors such as lipopolysaccharide (LPS; endotoxin) that influence metabolic homeostasis. Rifaximin is a well-tolerated antibiotic that may reduce LPS. Objective We sought to develop a method to accurately assess postprandial endotoxemia and to determine whether rifaximin treatment improves metabolic homeostasis in obese humans with metabolic syndrome. Design and Setting Plasma LPS, adipose inflammation, glucose and lipid metabolism, and insulin sensitivity were evaluated in a clinical research setting. Participants Twelve obese human research participants with prediabetes or three features of metabolic syndrome participated. Intervention The research participants were randomized to placebo control or rifaximin soluble solid dispersion (80 mg/d) treatment groups and treated for 12 weeks. Outcome Measures We evaluated changes in insulin sensitivity with a euglycemic clamp; changes in lipid and glucose metabolism with oral lipid and glucose tolerance tests; changes in plasma LPS during the lipid tolerance test; and changes in adipose tissue and systemic inflammation by measuring inflammatory cytokines. Results Rifaximin treatment slightly worsened insulin sensitivity (P = 0.03), did not improve glucose or lipid homeostasis, and did not significantly improve adipose tissue inflammation. Our efforts to accurately assess plasma LPS using limulus amebocyte lysate assays revealed that the majority of LPS is masked from detection by limulus amebocyte lysate assays, but can be unmasked using a pretreatment step with protease. Unmasked LPS increases during the lipid tolerance test, but rifaximin treatment did not reduce this. Conclusions Rifaximin treatment did not lower plasma LPS or improve metabolic homeostasis in obese humans.

Introduction Nonhuman animal models have been used extensively to study orthodontic tooth movement (OTM). However, rodent models have disadvantages, including a reported reduction in bone volume during OTM. The purpose of this study was to determine the viability of a skeletal anchorage and the effect of low force (∼3 cN) on interradicular bone volume during OTM. Methods Ninety Sprague-Dawley rats were divided into 5 time points. A miniscrew and a nickel titanium coil spring placed a load of 3 cN (experimental) or 0 cN (sham) on the maxillary first molar in a split-mouth design. Displacement of the first molar and bone volume/total volume (BV/TV) in the interradicular region were quantified. Results The success rate of the miniscrew was 98.9% (89 out of 90). Linear and angular tooth movement increased steadily (mean 0.1 mm/wk, 0.48 mm at 40 days). BV/TV was significantly reduced between the tooth movement and non–tooth movement sides in the 3 cN group: by 13%, 23%, 15%, 23%, and 16% at 3, 7, 14, 28, and 40 days, respectively. Conclusions Our model resulted in efficient OTM without skeletal anchorage failure. BV/TV reduction was lower than in previous reports. This novel validated model is likely to be the basis for future studies.

Background Non-invasive transcranial direct current stimulation has been shown to modulate cortical excitability in various studies. Similarly, recent preliminary studies suggest that transcutaneous spinal direct current stimulation (tsDCS) may engender a modulation effect on spinal and cortical neurons. Objective The purpose of this study was to evaluate the dose-response effects of tsDCS in healthy subjects and thereby lay groundwork for expanding treatment options for patients with spinal cord injury (SCI). Methods Nine healthy subjects received each of the following 2 tsDCS conditions: Anodal and cathodal, in random order with at least 1 week washout period between each session. In order to test safety and dose response, various current intensities were used (2, 2.5 and 3 mA) for 20 minutes. The active electrode was placed vertically over T10-T11, and the reference electrode was placed over the left shoulder. To evaluate corticospinal excitability, motor evoked potentials over soleus muscle elicited by transcranial magnetic stimulation were measured. To assess spinal cord excitability, H- and M- wave over soleus muscle to calculate Hmax/ Mmax ratio were measured. Results Linear regression showed a dose response with cathodal tsDCS on motor evoked potentials measured from the left leg as well as with anodal tsDCS on Hmax/ Mmax ratio measured from the left leg. Conclusions These findings indicate tsDCS effects are dose-dependent. These effects should be investigated in a larger sample.

Background Arm care programs consisting of upper extremity strengthening and stretching have been recommended for injury prevention for pitchers of all ages. There has been no investigation into high school baseball coaches’ usage and perceptions of arm care programs to mitigate physical impairments associated with injuries in baseball players. # Hypothesis/Purpose The purpose of this study was to investigate the current usage of arm care programs by high school baseball coaches. The primary objective was to determine if coaches use group-based or individualized arm care programs. The secondary objective sought to determine if the use of arm care programs is influenced by coaches’ age, education, and experience level. Finally, this study explored the potential barriers to arm care implementation and high school baseball coaches’ current awareness and beliefs of injury prevention. # Study Design Descriptive cross-sectional survey # Methods A 29-item online survey was emailed to 18,500 high school baseball coaches throughout the United States. Data were collected for three months, and the response rate was 3.7%. # Results A total of 87.3% (n=571/654) of responding coaches use arm care programs with their players. Of coaches performing arm care, only 18.5% of 571 individualize their arm care exercises based on specific player needs. However, older and more experienced coaches are more likely to individualize their programs. Among the 12.7% (n=83/654) of coaches who do not use arm care programs, the two most commonly cited reasons for not implementing arm care were lack of observed benefit (41%) and insufficient staff (31%). Although 42% of 654 coaches recognized reduced shoulder mobility as a major contributor to injury, risk factors such as throwing with a fatigued arm, previous injury history, and throwing \> 8 months per year were not consistently identified as primary risk factors. # Conclusion The results of this study suggest that the majority high school baseball coaches implement group-based arm care exercise programs to prevent injury. Lack of confidence in the effectiveness and staffing limitations were major barriers to implementation of arm care programming. However, the responding coaches exhibited inconsistent risk factor awareness and dated injury prevention beliefs. Therefore, better educational collaboration between rehabilitation professionals and high school coaches regarding injury risk factors and preventative strategies is warranted. # Level of Evidence Level 3

Background: Despite disproportionate rates of diabetes among Appalachian residents, barriers to attending clinical appointments have not been fully explored. We examined the association between barriers to clinic attendance, A1c, and self-care. Methods: We report baseline cross-sectional data from an ongoing study of participants in six counties in rural Appalachia Kentucky. Barriers to clinic attendance were measured using a 25-item checklist adapted from the Chronic Care Model and self-care was measured using a summary score from Toobert’s Diabetes Self-Care Activities. Linear regression models were fit with varying levels of adjustment. Results: Most study participants (N=356) where White (n=349), women (n=230), and had health insurance (n=349). Average A1c was 7.7% (SD=1.7%). No barriers were reported by 37.4% of participants. In fully adjusted models, not being worried about diabetes was significantly associated with diabetes self-care. Inaccessible transportation and co-payment, and the belief that God (but not them) will help their diabetes were significantly associated with A1c (Table 1). Conclusions: Both logistical and cognitive barriers obstruct clinic attendance in this sample. Additional aspects or barriers to clinical attendance could be cognitive or emotional, such as social support and cultural norms. Future research should develop interventions for these logistical and cognitive barriers. Disclosure B. L. Smalls: None. M. Lacy: None. L. Hieronymus: None. P. Westgate: None. M. Azam: None. S. C. Westneat: None. N. Schoenberg: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112136)

BACKGROUND: Patient-reported measures guide physicians in clinical decision making and therefore it is critical to determine what clinical factors are associated with these scores. Psychological and physical factors are commonly studied separately in patients with rotator cuff tears to determine their influence on outcomes. It is well established that psychological distress and scapular motion change in the presence of a symptomatic rotator cuff tear. However, these factors have not been studied simultaneously in a clinical setting to determine their association with shoulder outcome scores. QUESTION/PURPOSE: After controlling for relevant confounding variables, what physical and psychological factors are associated with better (1) American Shoulder and Elbow Surgeons (ASES) scores for function, (2) ASES pain scores, and (3) total ASES scores? METHODS: Fifty-nine patients with a potential symptomatic rotator cuff tear were recruited and agreed to participate in this cross-sectional study. Of those, 85% (50 of 59) met eligibility criteria for a primary diagnosis of an MRI-confirmed symptomatic partial-thickness or full-thickness rotator cuff tear without a history of shoulder surgery. Demographics, rotator cuff tear size, arm flexion, and clinical scapular motion during active arm flexion were evaluated by experienced examiners using standardized procedures. Patients completed the ASES questionnaire and the Optimal Screening for Prediction of Referral and Outcomes-Yellow Flag assessment form, which measures 11 different pain-related psychological distress symptoms. Three separate stepwise multiple linear regression analyses were performed for ASES pain, function, and total scores, with significance set at p < 0.05. RESULTS: This model found that ASES function scores were associated with four factors: older age, increased arm flexion, increased percentage of scapular external rotation during arm flexion, and increased scores for acceptance of chronic pain (adjusted r(2) = 0.67; p = 0.01). Those four factors appear to explain 67% of the observed variance in ASES function scores in patients with rotator cuff tears. Furthermore, increased percentage of scapular external rotation during arm flexion and decreased fear-avoidance beliefs related to physical activity scores (adjusted r(2) = 0.36; p < 0.01) were associated with better ASES pain scores. And finally, better ASES total scores were associated with four factors: increased arm flexion, increased percentage of scapular upward rotation, increased scapular external rotation during arm flexion, and decreased fear-avoidance beliefs related to physical activity scores (adjusted r(2) = 0.65; p < 0.001). CONCLUSION: Our results favor adopting a comprehensive biopsychological clinical assessment for patients with rotator cuff tears that specifically includes humeral and scapular motion, fear-avoidance behaviors, and pain coping behaviors along with demographics. These particular physical and psychological variables were found to be associated with the ASES and, therefore, should be clinically examined simultaneously and targeted as part of a tailored treatment plan. LEVEL OF EVIDENCE: Level II, prognostic study.

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 &lt, 80%) may be associated with extubation failure at 72 h in a cohort of neonates &lt, 30 weeks gestational age. Current-generation bedside high-resolution pulse oximeters provide saturation profiles that may be of use in identifying extubation readiness and failure. A larger prospective study that utilizes intermittent hypoxemia as an adjunct predictor for extubation readiness is warranted.

BACKGROUND Bronchodilator responses among preterm infants are heterogeneous. Bedside measurements may identify responders. STUDY DESIGN Respiratory measurements (Resistance, Compliance, FiO2) and pulse oximetry (SpO2) patterns were downloaded from infants

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.

Highlights • HEALing Communities Study is a parallel-group cluster randomized controlled trial. • Communities That HEAL intervention’s goal is to reduce opioid overdose deaths. • Structured consensus decision-making strategy guided study measure development. • More than 80 study measure specifications and a common data model were developed. • The study will provide methodology and longitudinal community data for research., Background Opioid overdose deaths remain high in the U.S. Despite having effective interventions to prevent overdose deaths, there are numerous barriers that impede their adoption. The primary aim of the HEALing Communities Study (HCS) is to determine the impact of an intervention consisting of community-engaged, data-driven selection, and implementation of an integrated set of evidence-based practices (EBPs) on reducing opioid overdose deaths. Methods The HCS is a four year multi-site, parallel-group, cluster randomized wait-list controlled trial. Communities (n = 67) in Kentucky, Massachusetts, New York and Ohio are randomized to active intervention (Wave 1), which starts the intervention in Year 1 or the wait-list control (Wave 2), which starts the intervention in Year 3. The HCS will test a conceptually driven framework to assist communities in selecting and adopting EBPs with three components: 1) A community engagement strategy with local coalitions to guide and implement the intervention; 2) A compendium of EBPs coupled with technical assistance; and 3) A series of communication campaigns to increase awareness and demand for EBPs and reduce stigma. An implementation science framework guides the intervention and allows for examination of the multilevel contexts that promote or impede adoption and expansion of EBPs. The primary outcome, number of opioid overdose deaths, will be compared between Wave 1 and Wave 2 communities during Year 2 of the intervention for Wave 1. Numerous secondary outcomes will be examined. Discussion The HCS is the largest community-based implementation study in the field of addiction with an ambitious goal of significantly reducing fatal opioid overdoses.

Objective A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants.Study Design Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation.Results A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56–0.74, all p Conclusion We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process.Key Points

Treatment of subjects who are obese/insulin resistant with the β3AR agonist mirabegron resulted in increased beige adipose tissue, without a change in brown adipose tissue (BAT), along with an improvement in glucose tolerance, HbA1c, and an increase in type 1 fibers in skeletal muscle. Pioglitazone has been demonstrated to increase beiging, and it has been demonstrated that combination of a thiazolidinedione with a β3AR agonist further increased beige adipocyte markers in vitro. The goal of this study was to determine whether combination therapy with pioglitazone and mirabegron would further increase beiging, BAT volume or activity, or skeletal muscle fiber type switching, and improve glucose homeostasis more than each drug separately. We randomized obese and insulin-resistant (IR) research participants to mirabegron (50 mg/day), pioglitazone (30 mg/day), or combination treatment groups. Adipose and muscle tissue biopsies and PET-CT scans were performed at baseline and after 10 weeks of treatment. Mitochondrial bioenergetics were determined in purified mitochondria from adipose tissue. Although mirabegron and pioglitazone treatment significantly induced SC WAT beiging separately, the combination of the two drugs resulted in less beiging than mirabegron treatment alone, and did not increase mitochondrial uncoupling. Furthermore, neither pioglitazone nor combination therapy increased BAT or fiber-type switching to type 1 fibers. Although each drug improved glucose homeostasis, the effect of the combination was not significantly additive. Analysis of mRNA expression revealed that pioglitazone or combination treatment induced the expression of p107, which promotes white versus brown adipose gene expression, suggesting a mechanism for inhibition of mirabegron-induced beiging by pioglitazone. These results suggest that pioglitazone inhibits mirabegron-induced beiging and does not augment other beneficial effects of mirabegron treatment. Disclosure P.A. Kern: None. H. Memetimin: None. B. Zhu: None. A.L. Confides: None. Z. Johnson: None. H.J. Vekaria: None. P. Westgate: None. P.G. Sullivan: None. E.E. Dupont-Versteegden: None. B. Finlin: None. Funding National Institutes of Health (DK112282)

Introduction The Diabetes Prevention Program, an intensive lifestyle change program, effectively reduces the risk of progression from prediabetes to type 2 diabetes but is underutilized. An implementation study using formative research was undertaken to increase Diabetes Prevention Program referrals at a primary care clinic. Study design A pragmatic, cluster randomized, mixed-methods study. Setting/particpants Clusters were teams of primary care clinicians from 2 primary care clinics. The 3 intervention clusters had 8–11 clinicians, and the 3 control clusters had 7–20 clinicians. Intervention Implementation activities occurred from December 2017 to February 2019. The activities included targeted clinician education, a prediabetes clinician champion, and a custom electronic health record report identifying patients with prediabetes. Main outcome measures The primary outcome was referral of patients with prediabetes to the institutional Diabetes Prevention Program. Study data, including patient demographic and clinical variables, came from electronic health record. Interviews with clinicians evaluated the implementation strategies. Generalized estimating equation analyses that accounted for multiple levels of correlation and interview content analysis occurred in 2019. Results Study clinicians cared for 2,992 patients with a prediabetes diagnosis or HbA1c indicative of prediabetes (5.7%–6.4%). Clinicians in the intervention clusters referred 6.9% (87 of 1,262) of patients with prediabetes to the Diabetes Prevention Program and those in the control clusters referred 1.5% (26 of 1,730). When adjusted for patient age, sex, race, HbA1c value, HbA1c test location, and insurance type, intervention clinicians had 3.85 (95% CI=0.40, 36.78) greater odds of referring a patient with prediabetes to the Diabetes Prevention Program. The 11 interviewed intervention clinicians had mixed opinions about the utility of the interventions, reporting the prediabetes clinic champion (n=7, 64%) and educational presentations (n=6, 55%) as most helpful. Conclusions Intervention clinicians were more likely to make Diabetes Prevention Program referrals; however, the study lacked power to achieve statistical significance. Clinician interviews suggested that intervention components that triggered Diabetes Prevention Program referrals varied among clinicians.

Background Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH. Study design and methods We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO2 ) were monitored with high-resolution pulse oximeters 24 hours before and after RBC transfusion. Data were analyzed at three postnatal periods: Epoch 1, first week of life (1 to 7 days of life); Epoch 2, 2 to 4 weeks of life (8 to 28 days of life); and Epoch 3, 4 to 8 weeks of life. Results A total of 118 transfusions were analyzed. IH measures significantly decreased after transfusion in Epochs 2 and 3. PI significantly increased after transfusion, but it did not correlate with the decrease in IH measures. Mechanical ventilation, fraction of inspired oxygen (FiO2 ), and IH measures influenced the effects on oxygenation. Conclusions RBC transfusion improved IH after the first week of life. The benefit in IH did not correlate with PI increase after transfusion. Pretransfusion respiratory support and IH measures predicted the effect of transfusion on oxygenation.

Background: This study tested the influence of the ‘Protect Their Future’ video intervention on adult intentions to vaccinate their adolescents.Method: The study included 529 parents of 11- to 19-y...

OBJECTIVES: Determine the incidence of apnea in preterm and term infants after deep sedation (DS) compared with general anesthesia (GA). METHODS: A retrospective chart review was performed on infants who underwent elective DS or GA from January 2008 to December 2013, were RESULTS: There were 61 DS encounters (24 preterm and 37 term) and 175 GA encounters (120 preterm and 55 term) that met inclusion criteria. No recorded apneic events in either preterm or term infants were recorded after DS. After GA, 1.7% of infants had apneic events (2.5% preterm and 0 term; P = .57 versus DS). All events occurred within 2 hours of monitoring in recovery. CONCLUSIONS: None of the infants had apnea after DS. Rates from the literature would suggest that 2 to 6 of the preterm DS subjects should have experienced postsedation apnea. Sampled GA subjects had a rate of 2.5% in preterm infants exhibiting apnea after GA. Although the post-DS apnea rate is lower than what has been previously published, the small sample size and limitations of a retrospective design prevent us from directing a change in postsedation monitoring recommendations. However, we do support the need for prospective studies with strict monitoring criteria to reveal the true risk of post-DS apnea.

Objective: The purpose of this study was to quantitatively assess dentoalveolar and skeletal compensations in patients with untreated unilateral cleft lip and palate (UCLP). We hypothesized that there are significant skeletal and dental adaptations in UCLP cases compared to a comparison maxillary crossbite group. Design: A convenience retrospective sample of 30 patients with UCLP and a comparison group of 30 patients with unilateral posterior crossbite without CLP. Cone-beam computed tomography scans (CBCTs) were used to evaluate dental and skeletal compensations. In addition, alveolar bone thickness was measured at 2-mm increments in mesiodistal and faciolingual cross-sectional views along the long axis of the central incisors. Alveolar bone height was measured, and the percentage of root length supported by bone was calculated. Results: Compensations for unilateral cleft lip and palate were restricted to the cleft site and adjacent structures. Dental compensations include alteration in the position of cleft-adjacent maxillary incisors and maxillary canines. No gross skeletal compensations were found. Alveolar support of cleft adjacent incisors was similar to controls except for measurements in the most coronal and apical regions. The cleft group contralateral incisors exhibited buttressing effects and had significantly higher alveolar thickness in the coronal half of the tooth. There was less (5%) alveolar coverage of the cleft-facing aspect of the central incisor root than all other incisors. Conclusion: The bone adaptation to the presence of a cleft was localized in the vicinity of the cleft, and adaptations in the mandible were not apparent.

OBJECTIVE To compare the prevalence of disruptive behavior problems between preschool-aged children with hearing loss and normal hearing. STUDY DESIGN Cross-sectional study. SETTING Tertiary academic center. PATIENTS Caregivers of children (2-5 yr old) with normal hearing (NH) (n = 39), hearing loss using hearing aid(s) (HA) (n = 29), or cochlear implant(s) (CI) (n = 21). INTERVENTION(S) Demographic information and a mental health history were obtained. Child behavior and language development were assessed. MAIN OUTCOME MEASURE(S) The Young Child-Diagnostic Interview Schedule for Children-IV and the MacArthur-Bates Communication Development Inventory III. RESULTS Distributions of race, socioeconomic status, insurance status, and parental home situation (single versus two parent family) were similar across all groups. Parents of children with hearing loss were significantly more likely to report behavior problems (HA = 41%, CI = 38%) than parents of NH children (10%; p = 0.002). Children with hearing loss were significantly more likely to meet diagnostic criteria for oppositional defiant disorder (HA = 48%, CI = 48%) than NH children (23%; p = 0.02). More NH children (8%) than hearing impaired children (0%) had accessed mental health services (p = 0.08). NH children were found to have more advanced language development than hearing-impaired children (p

Purpose Although computer-aided craniofacial reconstructions allow for simulation of hard tissue changes, the prediction of the final soft tissue facial changes remains a challenge. The purpose of the present study was to evaluate the 3-dimensional (3D) soft tissue changes in patients undergoing 2-jaw orthognathic surgery. Patients and Methods For the present retrospective cohort study, 40 consecutive patients (11 men and 29 women; mean age 23.5 ± 4.9 years) who had undergone 2-jaw orthognathic surgery were selected. We obtained the medical and dental records from 3 weeks before surgery and 6 months after surgery. We used image processing software to segment, superimpose, and quantify the hard and soft tissue displacements in 3 dimensions before and after surgery at 15 paired locations. The soft tissue and hard tissue changes were determined through quantification of homologous landmark displacements between the preoperative and postoperative computed tomography data. We measured the 3D soft and hard tissue changes and the anteroposterior, inferosuperior, and transverse components of the changes. We quantified the ratios between the soft and hard tissue changes, tested Pearson's correlation between these changes, and developed a predictive regression equation for the observations at each location. Results We found that soft tissue movement followed the hard tissue movement, with a correlation nearly equal to 0.9 (range 0.85 to 0.98), suggesting that in general the soft tissues of the maxillary and mandibular landmarks are affected similarly by the skeletal movements. The anteroposterior component of the soft tissue 3D displacements followed the hard tissue movement with a ratio greater than 0.9 and with high correlation (r > 0.9) in the mandible. Conclusion The results of the present study provide surgeons with a ratio of hard to soft tissue change and the strength of the correlations, which will allow for more accurate 3D predictions for both midline and lateral structures in bimaxillary orthognathic surgical cases. In addition, predictive equations for various landmarks were developed and can be used in computer-based prediction programs to aid in treatment planning of soft tissue changes.

Objectives/Hypothesis To assess the efficacy of a patient navigator intervention to decrease nonadherence to obtain audiological testing following failed screening, compared to those receiving the standard of care. Methods Using a randomized controlled design, guardian-infant dyads, in which the infants had abnormal newborn hearing screening, were recruited within the first week after birth. All participants were referred for definitive audiological diagnostic testing. Dyads were randomized into a patient navigator study arm or standard of care arm. The primary outcome was the percentage of patients with follow-up nonadherence to obtain diagnostic testing. Secondary outcomes were parental knowledge of infant hearing testing recommendations and barriers in obtaining follow-up testing. Results Sixty-one dyads were enrolled in the study (patient navigator arm = 27, standard of care arm = 34). The percentage of participants nonadherent to diagnostic follow-up during the first 6 months after birth was significantly lower in the patient navigator arm compared with the standard of care arm (7.4% vs. 38.2%) (P = .005). The timing of initial follow-up was significantly lower in the navigator arm compared with the standard of care arm (67.9 days after birth vs. 105.9 days, P = .010). Patient navigation increased baseline knowledge regarding infant hearing loss diagnosis recommendations compared with the standard of care (P = .004). Conclusions Patient navigation decreases nonadherence rates following abnormal infant hearing screening and improves knowledge of follow-up recommendations. This intervention has the potential to improve the timeliness of delivery of infant hearing healthcare; future research is needed to assess the cost and feasibility of larger scale implementation. Level of Evidence 1b. Laryngoscope, 127:S1–S13, 2017

Objectives/Hypothesis Factors affecting access to healthcare is an expanding area of research. This study seeks to identify factors associated with no-show rates in an academic otolaryngology practice to improve clinical efficiency and patient access to care. Study Design Retrospective review. Methods A retrospective review of scheduled clinical appointments from February 1, 2015 to January 30, 2016 at a single academic otolaryngology department was performed. Statistical analysis was completed to examine the association of no-show rates with the following: otolaryngology subspecialty, clinic location (e.g., main campus vs. satellite), patient demographic factors, attending seniority, temporal factors, insurance types, rurality, and visit type. Results There was an overall no-show rate of 20% for 22,759 scheduled clinic visits. Satellite clinics had the highest no-show rates at 25% (P

Background: Circadian rhythms are characterized by approximate 24-hour oscillations in physiological and behavioral processes. Disruptions in these endogenous rhythms, most commonly associated with shift work and/or lifestyle, are recognized to be detrimental to health. Several studies have demonstrated a high correlation between disrupted circadian rhythms and metabolic disease. The aim of this study was to determine which metabolic parameters correlate with physiological measures of circadian temperature amplitude (TempAmp) and stability (TempStab). Methods: Wrist skin temperature was measured in 34 subjects (ages 50 to 70, including lean, obese, and diabetic subjects) every 10 minutes for 7 consecutive days. Anthropometric measures and fasting blood draws were conducted to obtain data on metabolic parameters: body mass index, hemoglobin A1C, triglycerides, cholesterol, high-density lipoprotein, and low-density lipoprotein. A history of hypertension and current blood pressure was noted. Results: Analysis of the data indicated a substantial reduction in TempAmp and TempStab in subjects with metabolic syndrome (three or more risk factors). To determine the impact of individual interdependent metabolic factors on temperature rhythms, stepwise multilinear regression analysis was conducted using metabolic syndrome measurements. Interestingly, only triglyceride level was consistently correlated by the analysis. Triglyceride level was shown to contribute to 33% of the variability in TempAmp and 23% of the variability in TempStab. Conclusion: Our results demonstrate that elevated triglycerides are associated with diminished TempAmp and TempStab in human subjects, and triglycerides may serve as a primary metabolic predictor of circadian parameters., To determine the relationship between metabolic factors and circadian parameters, fasting blood labs and wrist temperature data were collected. Statistical analysis was performed and revealed triglycerides as a primary predictor.

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.

Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. We obtained 31 echocardiography observations. Mean ΔPI (−0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

Background Child care workers are among the lowest paid US workers and experience a wide array of health concerns. The physical and mental demands of their job and the lack of employer-provided health-insurance increase health risks. The Caring and Reaching for Health (CARE) study evaluated a 6-month Healthy Lifestyles intervention targeting child care workers’ physical activity (primary outcome), other health behaviors, and their workplace health environment. Methods Eligible child care centers, defined as being in operation for at least 2 years and employing at least four staff, were enrolled into CARE’s cluster-randomized trial. Centers and their child care staff were randomly assigned to either the Healthy Lifestyles (HL) intervention arm or the Healthy Finances (HF) attention control arm using a block randomization approach. Intervention components were delivered through in-person workshops, center-level displays, informational magazines, director coaching, electronic messaging, and an interactive website. Outcome measures were collected during center visits at baseline and immediately post-intervention by trained data collectors blinded to center arm assignment. Workers’ physical activity was assessed with accelerometers, worn for 7 days. Secondary outcome measures included biometric assessments of health and fitness, web-based surveys about health behaviors, and an environmental audit of workplace supports for health. Multi-level linear mixed models assessed worker- and center-level changes in these outcomes. Results Participants included 553 child care workers representing 56 centers (HL = 250 staff/28 centers, HF = 303 staff/28 centers). At 6 months, moderate-to-vigorous physical activity declined slightly in both arms (− 1.3 min/day, 95% CI: − 3.0, 0.3 in HL; − 1.9 min/day, 95% CI: − 3.3, − 0.5 in HF), but there was no significant group by time interaction. Several secondary outcomes for other health behaviors and workplace health environment showed improvements in favor of the intervention arm, yet differences did not remain statistically significant after adjustment for multiple comparisons. Conclusions While the Healthy Lifestyles intervention did not improve health behaviors or the workplace health environment, results confirmed the pressing need to focus on the health of child care workers. Future interventions should focus on prevalent health issues (e.g., weight, stress), include both high-tech and high-touch intervention strategies, and address work conditions or other social determinants of health (e.g. wages) as a means of improving the health of these essential workers. Trial registration Care2BWell: Worksite Wellness for Child Care (NCT02381938).

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

Background and Purpose— A sensory-based intervention called peripheral nerve stimulation can enhance outcomes of motor training for stroke survivors with mild-to-moderate hemiparesis. Further research is needed to establish whether this paired intervention can have benefit in cases of severe impairment (almost no active movement). Methods— Subjects with chronic, severe poststroke hemiparesis (n=36) were randomized to receive 10 daily sessions of either active or sham stimulation (2 hours) immediately preceding intensive task-oriented training (4 hours). Upper extremity movement function was assessed using Fugl–Meyer Assessment (primary outcome measure), Wolf Motor Function Test, and Action Research Arm Test at baseline, immediately post intervention and at 1-month follow-up. Results— Statistically significant difference between groups favored the active stimulation group on Fugl–Meyer at postintervention (95% confidence interval [CI], 1.1–6.9; P =0.008) and 1-month follow-up (95% CI, 0.6–8.3; P =0.025), Wolf Motor Function Test at postintervention (95% CI, −0.21 to −0.02; P =0.020), and Action Research Arm Test at postintervention (95% CI, 0.8–7.3; P =0.015) and 1-month follow-up (95% CI, 0.6–8.4; P =0.025). Only the active stimulation condition was associated with (1) statistically significant within-group benefit on all outcomes at 1-month follow-up and (2) improvement exceeding minimal detectable change, as well as minimal clinically significant difference, on ≥1 outcomes at ≥1 time points after intervention. Conclusions— After stroke, active peripheral nerve stimulation paired with intensive task–oriented training can effect significant improvement in severely impaired upper extremity movement function. Further confirmatory studies that consider a larger group, as well as longer follow-up, are needed. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02633215.

Background Locomotor training with a robot-assisted gait orthosis (LT-RGO) and transcranial direct current stimulation (tDCS) are interventions that can significantly enhance motor performance after spinal cord injury (SCI). No studies have investigated whether combining these interventions enhances lower extremity motor function following SCI. Objective Determine whether active tDCS paired with LT-RGO improves lower extremity motor function more than a sham condition, in subjects with motor incomplete SCI. Methods Fifteen adults with SCI received 36 sessions of either active (n = 9) or sham (n = 6) tDCS (20 minutes) preceding LT-RGO (1 hour). Outcome measures included manual muscle testing (MMT; primary outcome measure); 6-Minute Walk Test (6MinWT); 10-Meter Walk Test (10MWT); Timed Up and Go Test (TUG); Berg Balance Scale (BBS); and Spinal Cord Independence Measure-III (SCIM-III). Results MMT showed significant improvements after active tDCS, with the most pronounced improvement in the right lower extremity. 10MWT, 6MinWT, and BBS showed improvement for both groups. TUG and SCIM-III showed improvement only for the sham tDCS group. Conclusion Pairing tDCS with LT-RGO can improve lower extremity motor function more than LT-RGO alone. Future research with a larger sample size is recommended to determine longer-term effects on motor function and activities of daily living.

Objectives Epiphora is a common presenting complaint in infants affecting up to 6% of infants in the United States. It is most frequently due to congenital anomalies of the nasolacrimal duct system, termed congenital nasolacrimal duct obstruction (CNLDO). Nasolacrimal duct probing is widely accepted as the primary surgical intervention in cases that fail conservative management. Recently, nasal endoscopy has been combined with traditional probing to improve success rates and outcomes. Several studies have been conducted, but the results have been inconclusive overall. The goal of this systematic review is to examine the existing literature on the role of nasal endoscopy during nasolacrimal duct probing and evaluate patient outcomes. Methods A systematic search was performed in PubMed, MEDLINE, The Cochrane Library, ClinicalTrials.gov, LILAC, and EMBASE to identify peer-reviewed research. Eligible studies were those containing original peer-reviewed research in English addressing nasolacrimal duct probing for congenital nasolacrimal duct obstruction in conjunction with nasal endoscopy. Two investigators independently reviewed all articles and extracted data. Bias was assessed using the Cochrane Collaboration's tool, the Newcastle-Ottawa Assessment scale, and the NIH Quality Assessment scale. Results A literature review ultimately yielded 11 articles that were selected and included in our analysis. Of the seven case series, the success rate was 92.5% for a total of 492 eyes. Of the four cohort/case-control studies, the success rate in conventional probings was 75.3% for a total of 293 eyes. In probings with nasal endoscopy, the success rate was 95.3% for 162 eyes. Overall, there was a high risk of bias and variation in data reporting amongst studies. Conclusion Infants with congenital nasolacrimal duct obstruction that does not resolve with conservative treatment often require surgical intervention. Based on this systematic review of the current literature, nasal endoscopy is a useful adjunct for nasolacrimal duct probing.

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.

OBJECTIVE: Determine whether somatosensory stimulation affects outcomes of motor training for moderate-to-severe upper extremity hemiparesis less than 12 months post-stroke. DESIGN: 55 adults participated in 18 intervention sessions pairing 2 hours of active (n=33) or sham (n=22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. Wolf Motor Function Test, Action Research Arm Test, Fugl-Meyer Assessment, and Stroke Impact Scale were administered at baseline, post-intervention, and 1- and 4-month follow-up. RESULTS: Statistically significant between-groups differences favored the active condition on Wolf Motor Function Test at post (p=0.04) and Action Research Arm Test at post (p=0.02), 1-month (p=0.01), and 4-month (p=0.01) but favored the sham condition on Stroke Impact Scale at 1-month (p=0.03). There were no significant between-groups differences on Fugl-Meyer Assessment. CONCLUSION: Somatosensory stimulation can improve objective outcomes of motor training for moderate-to-severe hemiparesis less than 12 months after stroke, although the magnitude of between-groups differences in this study needs to be determined if they are clinically relevant. Future studies should investigate the intervention’s impact on disability and functional recovery for this population as well as neurophysiological mechanisms underlying intervention effects.

BACKGROUND. The induction of beige adipocytes in s.c. white adipose tissue (WAT) depots of humans is postulated to improve glucose and lipid metabolism in obesity. The ability of obese, insulin-resistant humans to induce beige adipose tissue is unknown. METHODS. We exposed lean and obese research participants to cold (30-minute ice pack application each day for 10 days of the upper thigh) or treated them with the β3 agonist mirabegron. We determined beige adipose marker expression by IHC and quantitative PCR, and we analyzed mitochondrial bioenergetics and UCP activity with an Oxytherm system. RESULTS. Cold significantly induced UCP1 and TMEM26 protein in both lean and obese subjects, and this response was not associated with age. Interestingly, these proteins increased to the same extent in s.c. WAT of the noniced contralateral leg, indicating a crossover effect. We further analyzed the bioenergetics of purified mitochondria from the abdominal s.c. WAT of cold-treated subjects and determined that repeat ice application significantly increased uncoupled respiration, consistent with the UCP1 protein induction and subsequent activation. Cold also increased State 3 and maximal respiration, and this effect on mitochondrial bioenergetics was stronger in summer than winter. Chronic treatment (10 weeks; 50 mg/day) with the β3 receptor agonist mirabegron induces UCP1, TMEM26, CIDEA, and phosphorylation of HSL on serine660 in obese subjects. CONCLUSION. Cold or β3 agonists cause the induction of beige adipose tissue in human s.c. WAT; this phenomenon may be exploited to increase beige adipose in older, insulin-resistant, obese individuals. TRIAL REGISTRATION. Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02596776","term_id":"NCT02596776"}}NCT02596776, {"type":"clinical-trial","attrs":{"text":"NCT02919176","term_id":"NCT02919176"}}NCT02919176. FUNDING. NIH ({"type":"entrez-nucleotide","attrs":{"text":"DK107646","term_id":"187677713","term_text":"DK107646"}}DK107646, {"type":"entrez-nucleotide","attrs":{"text":"DK112282","term_id":"187405426","term_text":"DK112282"}}DK112282, P20GM103527, and by CTSA grant UL1TR001998).

Objectives This study aimed to determine whether an enhanced bioavailable curcumin formulation, CurQfen®, would improve circulating cardiovascular disease–related blood biomarkers and arterial function in young (age 18–35 y), obese (body mass index ≥ 30.0 kg/m2) men. Methods This double-blinded, placebo-controlled trial evaluated 22 men. The participants were matched based on body mass index and randomized to the intervention (curcumin formulated with fenugreek soluble fiber, for enhanced absorption) or control (fenugreek soluble fiber) group for 12 wk at 500mg/d without dietary modification or exercise. Blood samples and endothelial function measures were acquired at 0 and 12 wk, and blood samples were analyzed for cardiovascular disease–related blood biomarkers. Furthermore, central (aortic) blood pressure and augmentation index were monitored at 0, 4, 8, and 12 wk. Results After 12 wk of intervention, homocysteine levels were lower (curcumin before: 12.22 ± 2.29 µg/mL, after: 8.62 ± 1.02 µg/mL versus placebo before: 9.45 ± 0.84 µg/mL, after: 11.84 ± 1.63 µg/mL; P = 0.04) and high-density lipoprotein levels were higher (curcumin before: 40.77 ± 5.37 mg/dL, after: 54.56 ± 11.72 mg/dL versus placebo before: 61.20 ± 5.76 mg/dL, after: 48.82 ± 5.49 mg/dL; P = 0.04) in the curcumin group relative to the placebo group. However, there was no significant difference in changes between the circulating concentrations of glucose, insulin, leptin, adiponectin, or oxidative stress biomarkers in the curcumin group compared with the placebo group (P > 0.05). No changes were found with endothelial function, augmentation index, or central blood pressure in the curcumin group compared with the placebo group (P > 0.05). Conclusions Our data provide evidence for an enhanced bioavailable curcumin to improve homocysteine and high-density lipoprotein concentrations, which may promote favorable cardiovascular health in young, obese men. Improvements in endothelial function or blood pressure were not observed with curcumin supplementation, thus further investigation is warranted.

Objectives This study investigated the feasibility of modulating bilateral corticospinal excitability with different polarities of transcutaneous spinal direct current stimulation (tsDCS) in chronic, incomplete spinal cord injury (SCI). Methods Six subjects with chronic incomplete SCI (>12 months post injury) participated in this crossover study. Intervention consisted of 3 sessions, separated by at least 1 week, in which each subject received the conditions cathodal, anodal, and sham tsDCS. Stimulation was delivered at 2.5 mA for 20 minutes with the active electrode positioned over the spinous processes of T10-T11 and the reference electrode over left deltoid. To measure the effects of tsDCS on corticospinal excitability, motor evoked potentials (MEPs) from transcranial magnetic stimulation were measured bilaterally from soleus before and after tsDCS. Results Five subjects completed all 3 sessions. One subject withdrew after 2 sessions due to complications unrelated to the study. MEPs were measurable in 5 subjects. No significant differences in change of MEP amplitudes were found between the 3 conditions. However, there were trends that indicated laterality of response, particularly with cathodal tsDCS increasing corticospinal excitability contralateral to the reference electrode and decreasing corticospinal excitability ipsilateral to the reference electrode. Conclusion Corticospinal excitability may be modulated with laterality by tsDCS in individuals with chronic, incomplete SCI. Further research is needed to 1) determine whether different placement of the reference electrode can lead to uniform modulation bilaterally, and 2) reveal whether these alterations in corticospinal excitability can lead to improved movement function in individuals with chronic, incomplete SCI.

Background Brain-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. Objective To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. Methods This 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. Results 67 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). Conclusion Plasma 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.