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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 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.

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.

To assess the proposed shortened tools based on the Finnegan neonatal abstinence scoring tool (FNAS) for relative clinical utility.Retrospective study comparing shortened tools with FNAS on need for treatment, medication initiation cutoff score agreement, and length of treatment in 369 infants with prenatal opioid exposure using estimated areas under the receiver operating characteristic curves, Pearson and Spearman correlations, and proportion correctly classified, sensitivity, and specificity.The tools by Gomez et al. and Chervoneva et al. are most predictive of the FNAS cut-off values to initiate treatment, have cutoff values that best align with the FNAS cutoff values, and strongly correlate with the FNAS (r ≥ 0.88 corresponding to treatment initiation, r ≥ 0.83 during first 10 days of treatment).The tools of Gomez and Chervoneva demonstrated potential clinical usefulness by strongly associating with the need for treatment and monitoring the course of NAS therapy.

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.

OBJECTIVE: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. The present study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease. DESIGN: ALS patients (N = 102) being treated in 3 multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry, and psychological health every 3 months for up to 18 months. MAIN OUTCOME MEASURE: Psychological health composite. RESULTS: In multilevel dyadic models, patients and spouses had similar levels of financial worry and loneliness. Both patients and spouses had worse psychological health with higher loneliness, but only spouses had worse psychological health with higher financial worry. Significant interactions with age and disease severity indicated that older spouses were more affected by loneliness than were younger spouses, and patients with less severe disease were more affected by financial worry than patients with more severe disease. CONCLUSION: The results provide good support for socioemotional selectivity theory’s implications for psychological health in a strong test of the theory.

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 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 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

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.

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.

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.

Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ9-tetrahydrocannabinol (Δ9-THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ9-THC and placebo and then received a range of Δ9-THC doses (0, 5, 15 and a “high” dose of either 25 or 30 mg). Responses on a drug-discrimination task, subjective effects questionnaire, psychomotor performance tasks, and physiological measures were assessed. Δ9-THC dose-dependently increased drug-appropriate responding, ratings on “positive” visual analog scale (VAS) items (e.g., Good Effects, Like Drug, Take Again), and items related to intoxication (e.g., High, Stoned). Δ9-THC also dose-dependently impaired performance on psychomotor tasks and elevated heart rate. Sex differences on VAS items emerged as a function of dose. Women exhibited significantly greater subjective responses to oral drug administration than men at the 5 mg Δ9-THC dose, whereas men were more sensitive to the subjective effects of the 15 mg dose of Δ9-THC than women. These results demonstrate dose-dependent separation in the subjective response to oral Δ9-THC administration by sex, which might contribute to the differential development of problematic cannabis use.

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).

In a recent study, repeated cold application induced beiging in subcutaneous white adipose tissue (SC WAT) of humans independent of body mass index. To identify factors that promote or inhibit beiging, we performed multiplex analysis of gene expression with the Nanostring nCounter system (the probe set contained genes for specific immune cell markers, cytokines, and chemokines) on the SC WAT from lean subjects. Multiple correlations analysis identified mast cell tryptase and CCL26, a chemokine for mast cells, as genes whose change correlated positively with the change in UCP1 in SC WAT, leading to the hypothesis that mast cells promote SC WAT beiging in response to cold. We quantified mast cell recruitment into SC WAT and degranulation. Mast cells increased in number in SC WAT in lean subjects, and there was an increase in the number of degranulated mast cells in both lean subjects and subjects with obesity. We determined that norepinephrine stimulated mast cell degranulation and histamine release in vitro. In conclusion, cold stimulated adipose tissue mast cell recruitment in lean subjects and mast cell degranulation in SC WAT of all research participants independent of baseline body mass index, suggesting that mast cells promote adipose beiging through the release of histamine or other products.

Background Intensive motor training is a therapeutic intervention that supports recovery of movement function after stroke by capitalizing on the brain's capacity for neuroplastic change. Peripheral nerve stimulation and transcranial direct current stimulation are neuromodulation techniques that can upregulate neuroplasticity and, in turn, enhance outcomes of motor training after stroke. Few studies have investigated possible adjuvant effects between peripheral nerve stimulation, transcranial direct current stimulation, and intensive motor training. Objective This proof-of-concept study investigated whether timing variations in neuromodulation paired with robot-assisted motor training effect differential outcomes for subjects with chronic, moderate-to-severe upper extremity impairment after stroke. Methods Ten subjects in the chronic phase (>12 months after stroke) of recovery completed the study. Subjects received 10 daily sessions of transcranial direct current stimulation either at the start (n = 4) or at the end (n = 6) of peripheral nerve stimulation preceding intensive motor training. Pre-post changes in motor function (Fugl-Meyer Assessment; Stroke Impact Scale) and neuroplasticity (transcranial magnetic stimulation) were assessed by condition. Results Significant improvement in Stroke Impact Scale (p = 0.02) and no change in Fugl-Meyer Assessment were associated with the start condition. No changes in Stroke Impact Scale and Fugl-Meyer Assessment were associated with the end condition. Only 1 subject in the start group had measurable neuroplastic responses and demonstrated an increase in ipsilesional cortical map volume. Only 1 subject in the end group had measurable neuroplastic responses and demonstrated a decrease in ipsilesional cortical map volume. Opposite shifts in ipsilesional cortical centers of gravity occurred relative to condition. Conclusion In cases of moderate-to-severe impairment after stroke, transcranial direct current stimulation at the start, rather than the end, of peripheral nerve stimulation prior to motor training may effect better functional outcomes. Future research with a larger sample size is needed to validate the findings of this proof-of-concept study.

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.

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.

Generalized estimating equations are routinely utilized for the marginal analysis of longitudinal data. In order to obtain consistent regression parameter estimates, these estimating equations must be unbiased. However, when certain types of time-dependent covariates are presented, these equations can be biased unless the working independence structure is used. Unfortunately, regression parameter estimation can be very inefficient with this structure because not all valid moment conditions are incorporated within the corresponding equations. Therefore, approaches have been proposed to utilize all valid moment conditions. However, these approaches assume that the data analyst knows the type of time-dependent covariate, although this likely is not the case in practice. Whereas hypothesis testing has been used to determine covariate type, we propose a novel strategy to select a working covariate type in order to avoid potentially high type II error rates with these hypothesis testing procedures. Parameter estimates resulting from our proposed method are consistent and have overall improved mean squared error relative to hypothesis testing approaches. Existing and proposed methods are compared in a simulation study and application example.

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 a rise 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 gestational age. PI and oxygen saturation (SpO(2)) were monitored with high-resolution pulse oximeters 24 hours pre and post RBC transfusion. Data was 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: One hundred eighteen transfusions were analyzed. IH measures significantly decreased post 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 (FiO(2)), 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. Pre transfusion respiratory support and IH measures predicted the effect of transfusion on oxygenation.

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 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.

No medications are approved for cannabis use disorder (CUD). Gamma-aminobutyric acid (GABA) reuptake is modulated by cannabinoid (CB) receptor agonists, and there are shared effects between CB agonists and the GABA reuptake inhibitor tiagabine. This overlapping neuropharmacology suggested that tiagabine might be useful for CUD. The study determined the ability of tiagabine maintenance to reduce cannabis self-administration using a placebo-controlled, double-blind, counterbalanced, within-subjects design. Nontreatment-seeking daily cannabis users (N = 12; 3 female, 9 male) completed two 12-day outpatient maintenance phases (0 or 12 mg of tiagabine/day). Each phase consisted of a safety session, 7 maintenance days, and 4 experimental sessions. 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% Δ9-tetrahydrocannabinol). Naturalistic cannabis use, the subjective, performance and physiological response to cannabis, as well as side effects, sleep quality, craving, other self-reported substance use, and observer ratings were also measured. Cannabis functioned as a reinforcer and produced prototypical effects (e.g., increased heart rate and ratings of "high"), but tiagabine generally did not impact the effects of cannabis, or alter naturalistic use. Furthermore, tiagabine produced small, but significant, increases on 2 subscales of a Marijuana Craving Questionnaire, and reductions in both the amount of time slept in the past 24 hr and ratings of positive mood upon awakening. These human laboratory results from a sample of nontreatment-seeking cannabis users do not support the potential efficacy of 12 mg of tiagabine as a stand-alone pharmacotherapy for CUD. (PsycINFO Database Record

Objective Vitamin E deficiency in premature infants has been associated with hemolytic anemia. Its incidence decreased after the supplementation of preterm formulas and parenteral nutrition with vitamin E. Despite this, some infants still develop hemolytic anemia and receive vitamin E. Study Design Retrospective analysis of 70 infants admitted to a level IV intensive care unit and who developed hemolytic anemia and were treated with vitamin E. Infants were classified into two groups based on whether or not they responded to vitamin E therapy. Statistical methods included the use of descriptive statistics and marginal logistic regression models. Results Low hematocrit and reticulocytosis before vitamin E administration were associated with adequate response to treatment. Thrombocytosis, iron treatment (duration and dose), gestational age, birth weight, and type of feedings were not. Infants who received a short duration of parenteral nutrition and were on oxygen responded to vitamin E therapy. Infants with a hematocrit ≤ 26% and reticulocyte of 36.1% were more likely to respond to vitamin E. Conclusion Although formulas and parenteral nutrition are supplemented with vitamin E; some preterm infants may still develop hemolytic anemia. Those with anemia, reticulocytosis, and oxygen requirement may benefit from additional vitamin E.

BACKGROUND AND PURPOSE Robot-assisted locomotor training on a bodyweight-supported treadmill is a rehabilitation intervention that compels repetitive practice of gait movements. Standard treadmill speed may elicit rhythmic movements generated primarily by spinal circuits. Slower-than-standard treadmill speed may elicit discrete movements, which are more complex than rhythmic movements and involve cortical areas. OBJECTIVE Compare effects of fast (i.e., rhythmic) versus slow (i.e., discrete) robot-assisted locomotor training on a bodyweight-supported treadmill in subjects with chronic, severe gait deficit after stroke. METHODS Subjects (N = 18) were randomized to receive 30 sessions (5 d/wk) of either fast or slow robot-assisted locomotor training on a bodyweight-supported treadmill in an inpatient setting. Functional ambulation category, time up and go, 6-min walk test, 10-m walk test, Berg Balance Scale, and Fugl-Meyer Assessment were administered at baseline and postintervention. RESULTS The slow group had statistically significant improvement on functional ambulation category (first quartile-third quartile, P = 0.004), 6-min walk test (95% confidence interval [CI] = 1.8 to 49.0, P = 0.040), Berg Balance Scale (95% CI = 7.4 to 14.8, P < 0.0001), time up and go (95% CI = -79.1 to 5.0, P < 0.0030), and Fugl-Meyer Assessment (95% CI = 24.1 to 45.1, P < 0.0001). The fast group had statistically significant improvement on Berg Balance Scale (95% CI = 1.5 to 10.5, P = 0.02). CONCLUSIONS In initial stages of robot-assisted locomotor training on a bodyweight-supported treadmill after severe stroke, slow training targeting discrete movement may yield greater benefit than fast training.

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.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.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).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.1b. Laryngoscope, 127:S1-S13, 2017.

Although brown adipose tissue (BAT) activity is increased by a cold environment, little is known of the response of human white adipose tissue (WAT) to the cold.We examined both abdominal and thigh subcutaneous (SC) WAT from 71 subjects who were biopsied in the summer or winter, and adipose expression was assessed after an acute cold stimulus applied to the thigh of physically active young subjects.In winter, UCP1 and PGC1α mRNA were increased 4 to 10-fold (p0.05) and 1.5 to 2-fold, respectively, along with beige adipose markers, and UCP1 protein was 3-fold higher in the winter. The seasonal increase in abdominal SC WAT UCP1 mRNA was considerably diminished in subjects with a BMI30 kg/m(2), suggesting that dysfunctional WAT in obesity inhibits adipose thermogenesis. After applying an acute cold stimulus to the thigh of subjects for 30 min, PGC1α and UCP1 mRNA was stimulated 2.7-fold (p0.05) and 1.9-fold (p = 0.07), respectively. Acute cold also induced a 2 to 3-fold increase in PGC1α and UCP1 mRNA in human adipocytes in vitro, which was inhibited by macrophage-conditioned medium and by the addition of TNFα.Human SC WAT increases thermogenic genes seasonally and acutely in response to a cold stimulus and this response is inhibited by obesity and inflammation.

Background Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention. Objective Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke. Methods In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, Wolf Motor Function Test, and Action Research Arm Test at baseline, post-intervention, and 1-month follow-up. Results No significant between-groups differences were found in mean heart rate (95% CI, -12.4-22.6; p = 0.23), mean systolic blood pressure (95% CI, -1.7-29.6; p = 0.21), or mean diastolic blood pressure (95% CI, -10.4-13.3; p = 0.08). A statistically significant between-groups difference on Fugl-Meyer at post-intervention favored the atomoxetine group (95% CI, 1.6-12.7; p = 0.016). Conclusion Atomoxetine combined with motor training appears safe and may optimize motor training outcomes after stroke.

To evaluate factors that can influence the Finnegan Neonatal Abstinence Score (FNAS). Retrospective analysis of 367 patients admitted to two level IV neonatal intensive care units. Linear mixed effects models were developed to evaluate daily census, time of the day, and day of the week as fixed effect predictors. The degree of influence that nurses had on FNAS variability was also estimated. Bivariate analyses showed that daily census and the time of day have significant influence on the FNAS in institution 1, with minimal clinical significance. The proportion of variation in the FNAS attributable to differences in nurses was of 9.8% and 5.1% for institutions 1 and 2, respectively (P

Constraint-based therapy and peripheral nerve stimulation can significantly enhance movement function after stroke. No studies have investigated combining these interventions for cases of chronic, mild-to-moderate hemiparesis following stroke.This study aims to determine the effects of peripheral nerve stimulation paired with a modified form of constraint-induced therapy on upper extremity movement function after stroke. Nineteen adult stroke survivors with mild-to-moderate hemiparesis more than 12 mo after stroke received 2 hours of either active (n = 10) or sham (n = 9) peripheral nerve stimulation preceding 4 hours of modified constraint-induced therapy (10 sessions).Active peripheral nerve stimulation enhanced modified constraint-induced therapy more than sham peripheral nerve stimulation (significance at P0.05), both immediately after intervention (Wolf Motor Function Test: P = 0.006 (timed score); P = 0.001 (lift score); Fugl-Meyer Assessment: P = 0.022; Action Research Arm Test: P = 0.007) and at 1-mo follow-up (Wolf Motor Function Test: P = 0.025 (timed score); P = 0.007 (lift score); Fugl-Meyer Assessment: P = 0.056; Action Research Arm Test: P = 0.028).Pairing peripheral nerve stimulation with modified constraint-induced therapy can lead to significantly more improvement in upper extremity movement function than modified constraint-induced therapy alone. Future research is recommended to help establish longitudinal effects of this paired intervention, particularly as it affects movement function and daily life participation.Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Understand the role that afferent input plays with regard to movement function; (2) Understand general concepts of delivering modified constraint-based therapy in stroke rehabilitation research; and (3) Understand the rationale for applying an adjuvant intervention to optimize outcomes of constraint-based therapy following stroke.Advanced: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.

Background Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes. Methods Studies were performed on adult mechanically ventilated patients in the University of Kentucky MICU (n = 60). We assessed PdiTw by measuring transdiaphragmatic pressure (Pdi) in response to bilateral twitch stimulation of the phrenic nerves using dual magnetic stimulators (Magstim 200). Pimax was determined by measuring airway pressure during a 30-second inspiratory occlusion. We also assessed the twitch and maximum force generation for diaphragms excised from control and septic mice. Results Both Pimax and PdiTw measurements were profoundly reduced for mechanically ventilated MICU patients when compared to normal reference values, e.g., Pimax averaged 56 % of the predicted value for normal subjects. For the ICU population as a whole, PdiTw and Pimax values correlated with each other (r2 = 0.373, p

The method of quadratic inference functions (QIF) is an increasingly popular method for the analysis of correlated data because of its multiple advantages over generalized estimating equations (GEE). One advantage is that it is more efficient for parameter estimation when the working covariance structure for the data is misspecified. In the QIF literature, the asymptotic covariance formula is used to obtain standard errors. We show that in small to moderately sized samples, these standard error estimates can be severely biased downward, therefore inflating test size and decreasing coverage probability. We propose adjustments to the asymptotic covariance formula that eliminate finite-sample biases and, as shown via simulation, lead to substantial improvements in standard error estimates, inference, and coverage. The proposed method is illustrated in application to a cluster randomized trial and a longitudinal study. Furthermore, QIF and GEE are contrasted via simulation and these applications.

Context:Recent establishment of G-codes by the US government requires therapists to report function limitations at initial evaluation. Limited information exists specific to the most common limitations in patients with shoulder pain.Objective:To describe the most commonly expressed shoulder limitations with activities and their severity/level of impairment from a patient’s perspective on the initial evaluation.Design:Descriptive.Setting:Patients reporting pain with overhead activity and seeking medical attention from one orthopedic surgeon were recruited as part of a cohort study.Patients:176 with shoulder superior labral tear from anterior to posterior (SLAP), subacromial impingement, combined SLAP and rotator cuff, and nonspecific (female = 53, age = 41 ± 13 y; male = 123, age = 41 ± 12 y).Interventions:Data were obtained on the initial visit from the Patient-Specific Functional Scale (PSFS) questionnaire. Three researchers extracted meaningful concepts from the PSFS and linked them to the International Classification of Functioning (ICF) categories according to established ICF linking rules.Results:176 participants yielded 765 meaningful concepts that were linked to the ICF with a 66% agreement between researchers before consensus. There were no differences between diagnoses. Of all patients, 88% reported functional limitations coded into meaningful concepts as represented by 10 ICF codes; 634 (83%) meaningful concepts were linked to the activities and participation domain while 129 (17%) were linked to the body function domain. Only 2 reported functional limitations that were considered nondefinable (nd). The overall average initial impairment score on the PSFS = 4 ± 2.5 out of 10 points.Conclusion:Meaningful concepts from the activities and participation domain were most commonly identified as functional limitations and were more prevalent than limitations from the body function domain. This information helps identify some of the most common limitations in patients with shoulder pain that therapists can use to efficiently document patient functional impairment.

ObjectiveTo develop a simplified Finnegan Neonatal Abstinence Scoring System (sFNAS) that will highly correlate with scores ≥8 and ≥12 in infants being assessed with the FNAS.Design, setting and participantsThis is a retrospective analysis involving 367 patients admitted to two level IV neonatal intensive care units with a total of 40 294 observations. Inclusion criteria included neonates with gestational age ≥37 0/7 weeks, who are being assessed for neonatal abstinence syndrome (NAS) using the FNAS. Infants with a gestational age MethodsA linear regression model based on the original FNAS data from one institution was developed to determine optimal values for each item in the sFNAS. A backward elimination approach was used, removing the items that contributed least to the Pearson’s correlation. The sFNAS was then cross-validated with data from a second institution.ResultsPearson’s correlation between the proposed sFNAS and the FNAS was 0.914. The optimal treatment cut-off values for the sFNAS were 6 and 10 to predict FNAS scores ≥8 and ≥12, respectively. The sensitivity and specificity of these cut-off values to detect FNAS scores ≥8 and ≥12 were 0.888 and 0.883 for a cut-off of 6, and 0.637 and 0.992 for a cut-off of 10, respectively. The sFNAS cross-validation resulted in a Pearson’s correlation of 0.908, sensitivity and specificity of 0.860 and 0.873 for a cut-off of 6, and 0.525 and 0.986 for a cut-off of 10, respectively.ConclusionThe sFNAS has a high statistical correlation with the FNAS, and it is cross-validated for the assessment of infants with NAS. It has excellent specificity and negative predictive value for identifying infants with FNAS scores ≥8 and ≥12.

To provide an estimate of the prevalence of celiac disease by race/ethnic origin in large sample of US population. Data from the 2009–2010 and 2011–2012 NHANES were combined and analyzed. The NHANES is a nationally representative survey with oversampling of certain minorities. Sample-based frequencies were reported and weighted frequencies were used to estimate prevalence. A total of 14,701 participants were checked for tissue transglutaminase (tTG) and endomysial (EMA) IgA antibodies. Seventy-four participants had positive tTG and/or EMA corresponding to prevalence of 0.79 % (95 % CI 0.54–1.04 %). Non-Hispanic white were more likely to be positive for both compared with other races (72.0 vs 31.7 %; p = 0.010) and less likely to be weakly positive for tTG but positive for EMA (3.6 vs 26.4 %; p = 0.03). The prevalence of positive serology according to race was as follows: 1.08 % (95 % CI 0.70–1.45 %) in non-Hispanic white, 0.23 % (95 % CI 0.03–0.43 %) in Mexican, 0.22 % (95 % CI 0.01–0.44 %) in non-Hispanic black, 0.38 % (95 % CI 0.00–0.89 %) in “other Hispanic,” and 0.15 % (95 % CI 0.00–0.34 %) in other races including multiracial and undeterminable in non-Hispanic Asian due to the presence of only one positive EMA test. 0.9 % of the NHANES sample participants followed gluten-free diet. Of this group of participants, 85 % were never diagnosed with celiac disease and 99 % of them had negative celiac disease serology. Potentially 0.79 % of the general US population demonstrate serologic evidence of celiac disease autoimmunity. The prevalence is 4–8 times higher among non-Hispanic white compared with other races. Close to 1 % of the population is electively following gluten-free diet despite having little evidence of the disease.