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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).

In the United States, diabetes is the seventh leading cause of death and continues to rise in prevalence, with type 2 diabetes accounting for 90–95% of all cases. Rates of diabetes in Kentucky, and, in particular, the Appalachian region, are among the highest in the nation and are increasing faster than the national average. Despite this disproportionate burden, barriers to clinical appointment attendance have not been fully explored in this population. This article examines the association among perceived barriers to clinical attendance, glycemic control, and diabetes self-care as part of an ongoing study. We used a 25-item checklist developed using the Chronic Care Model to assess participants’ barriers to clinic attendance. Glycemic control was assessed via A1C measurement. Diabetes self-care was assessed using the Summary of Diabetes Self-Care Activities measure. At the time of analysis, 123 of the 356 participants (34.6%) did not report any barriers to clinic attendance. For the remainder, the major reported barriers included forgetting appointments, inability to afford medicines or other treatment, and placing faith above medical care. The average A1C was 7.7%, and the average diabetes self-care summary score was 17.1 out of 35 points (with higher values indicating better self-care). Missing clinic appointments is associated with lower health outcomes, especially in vulnerable populations. This study can help educate clinic staff on perceived barriers to type 2 diabetes management among people with diabetes in Appalachia.

Background/aims This work is motivated by the HEALing Communities Study, which is a post-test only cluster randomized trial in which communities are randomized to two different trial arms. The primary interest is in reducing opioid overdose fatalities, which will be collected as a count outcome at the community level. Communities range in size from thousands to over one million residents, and fatalities are expected to be rare. Traditional marginal modeling approaches in the cluster randomized trial literature include the use of generalized estimating equations with an exchangeable correlation structure when utilizing subject-level data, or analogously quasi-likelihood based on an over-dispersed binomial variance when utilizing community-level data. These approaches account for and estimate the intra-cluster correlation coefficient, which should be provided in the results from a cluster randomized trial. Alternatively, the coefficient of variation or R coefficient could be reported. In this article, we show that negative binomial regression can also be utilized when communities are large and events are rare. The objectives of this article are (1) to show that the negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model and to explain why the estimates may differ; (2) to derive formulas relating the negative binomial overdispersion parameter k with the intra-cluster correlation coefficient, coefficient of variation, and R coefficient; and (3) analyze pre-intervention data from the HEALing Communities Study to demonstrate and contrast models and to show how to report the intra-cluster correlation coefficient, coefficient of variation, and R coefficient when utilizing negative binomial regression. Methods Negative binomial and over-dispersed binomial regression modeling are contrasted in terms of model setup, regression parameter estimation, and formulation of the overdispersion parameter. Three specific models are used to illustrate concepts and address the third objective. Results The negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model, although estimates may differ. Practical differences arise in regard to how overdispersion, and hence the intra-cluster correlation coefficient is modeled. The negative binomial overdispersion parameter is approximately equal to the ratio of the intra-cluster correlation coefficient and marginal probability, the square of the coefficient of variation, and the R coefficient minus 1. As a result, estimates corresponding to all four of these different types of overdispersion parameterizations can be reported when utilizing negative binomial regression. Conclusion Negative binomial regression provides a valid, practical, alternative approach to the analysis of count data, and corresponding reporting of overdispersion parameters, from community randomized trials in which communities are large and events are rare.

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.

Stepped wedge cluster trials are an increasingly popular alternative to traditional parallel cluster randomized trials. Such trials often utilize a small number of clusters and numerous time intervals, and these components must be considered when choosing an analysis method. A generalized linear mixed model containing a random intercept and fixed time and intervention covariates is the most common analysis approach. However, the sole use of a random intercept applies a constant intraclass correlation coefficient structure, which is an assumption that is likely to be violated given stepped wedge trials (SWTs) have multiple time intervals. Alternatively, generalized estimating equations (GEE) are robust to the misspecification of the working correlation structure, although it has been shown that small-sample adjustments to standard error estimates and the use of appropriate degrees of freedom are required to maintain the validity of inference when the number of clusters is small. In this article, we show, using an extensive simulation study based on a motivating example and a more general design, the use of GEE can maintain the validity of inference in small-sample SWTs with binary outcomes. Furthermore, we show which combinations of bias corrections to standard error estimates and degrees of freedom work best in terms of attaining nominal type I error rates.

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.

Purpose: Children who are deaf or hard of hearing (DHH) and who use hearing aids or cochlear implants are more likely than their peers with typical hearing to exhibit behavior problems. Although multiple evidence-based interventions for child behavior problems exist, they are rarely delivered to children who are DHH, and no rigorous randomized controlled trials have been conducted to determine their effects with this population. This protocol describes a study aiming to test the effectiveness of an evidence-based behavioral parent training intervention adapted for parents of young children who are DHH and simultaneously to assess key implementation outcomes and multilevel contextual factors influencing implementation. Method: The protocol for a Type 1 hybrid effectiveness–implementation trial of a behavioral parent training intervention for parents of young children who are DHH is presented, including details of the study design, participants, assessments, and analyses. Using a stakeholder-engaged, mixed-methods approach, we will test the effects of the intervention versus treatment as usual on parenting behaviors, child behaviors, and a range of secondary effectiveness outcomes, including adherence to using hearing aids and cochlear implants as well as measures of child speech and language. We will assess the acceptability, feasibility, fidelity, and costs of the intervention from the perspectives of peer coaches who deliver the intervention, hearing health care clinicians (including audiologists and speech-language pathologists), and administrators of programs serving young children who are DHH. Conclusions: Results of this trial will inform future efforts to close the gap between prevalence of behavioral problems in young children who are DHH and access to and use of evidence-based interventions to prevent and treat them. If effective, this intervention could be widely implemented using strategies informed by the findings of this study to benefit young children who are DHH and followed in hearing health care and their families.

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.

BackgroundThe stepped wedge cluster randomized trial (SW-CRT) design is now preferred for many health- related trials because of its flexibility on resource allocation and clinical ethics concerns. However, as a necessary extension of studying multiple interventions, multiphase stepped wedge designs (MSW-CRT) have not been studied adequately. Since estimated intervention effect from Generalized estimating equations (GEE) has a population-average interpretation, valid inference methods for binary outcomes based on GEE are preferred by public health policy makers.MethodsWe form hypothesis testing of add-on effect of a second treatment based on GEE analysis in an MSW-CRT design with limited number of clusters. Four variance-correction estimators are used to adjust the bias of the sandwich estimator. Simulation studies have been used to compare the statistical power and type I error rate of these methods under different correlation matrices.Results We demonstrate that an average estimator with t(I-3) can stably maintain type I error close to the nominal level with limited sample sizes in our settings. We show that power of testing the add-on effect depends on the baseline event rate, effect sizes of two interventions and the number of clusters. Moreover, by changing the design with including more sequences, power benefit can be achieved. ConclusionsFor designing the MSW-CRT, we suggest using more sequences and checking event rate after initiating the first intervention via interim analysis. When the number of clusters is not very large in MSW-CRTs, inference can be conduct using GEE analysis with an average estimator with t(I-3) sampling distribution.

Background: Preseason movement screening can identify modifiable risk factors, deterioration of function, and potential for injury in baseball players. Limited resources and time prevent high school baseball coaches from performing movement screens on their players. Hypothesis: The arm care screen (ACS) will be highly sensitive to detecting musculoskeletal risk factors. Study Design: Cross-sectional Level of evidence: Level 3 Methods: A total of 150 baseball players were independently scored on the ACS electronically by reviewing a video recording of each player’s screening performance. Discriminability of the ACS was determined with a 2 × 2 contingency table dichotomizing musculoskeletal risk factors as present or absent based on a predetermined cutoff value and those who passed or failed the corresponding ACS subtest. Results: High sensitivity was observed on the reciprocal shoulder mobility (0.89; 95% CI 0.81-0.94), 90/90 total body rotation (0.86; 95% CI 0.79-0.92), and lower body diagonal reach (0.85; 95% CI 0.78-0.91) tests of the ACS suggesting sufficient ability to identify musculoskeletal impairments and risk factors. Conclusion: The ACS is a simplistic screening tool that the coach can administer to discriminate between youth, high school, and college-level baseball players who possess musculoskeletal risk factors. The ACS subtests demonstrated high sensitivity for correctly identifying musculoskeletal risk factors common in baseball players and can be useful as a screening tool for baseball coaches developing arm care exercise programs. Clinical Relevance: A field-expedient screen could provide coaches the ability to identify musculoskeletal risk factors that need to be addressed to minimize injury risk factors in a time-efficient manner.

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.

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.

It has been theorized that incorporating strength, speed, and flexibility training regimes may improve the quality of the tennis serve. Efficient stroke quality during the serve improves velocity and diminishes injury risk in tennis players. However, no study in tennis has identified whether adequate musculoskeletal capacity is a factor that helps drive optimal serve mechanics. The aim of this study was to determine whether musculoskeletal capacity could predict efficient serve mechanics. A total of 46 professional women’s tennis players (age: 26 ± 3 years, body mass: 65 ± 5 kg, height: 1.74 ± 0.06 m) were studied. Musculoskeletal capacity parameters were evaluated by the tennis specific screen (TSS) with strength and flexibility measures. Serve mechanics were evaluated using the observational tennis serve analysis (OTSA) tool. The OTSA is scored using a 0–9 system. Multiple regression analysis revealed scapular dyskinesis on the non-dominant side during flexion to be predictive of OTSA score (r2 = 0.14, p-value = 0.008). However, the correlation is weak (r = 0.38), rendering a non-clinically significant relationship between scapular dyskinesis and serve mechanics. None of the other musculoskeletal parameters generated significant relationships to serve mechanics. This study demonstrated that in professional women’s tennis players there is no meaningful relationship between the TSS measurements and OTSA scores. In conclusion, musculoskeletal capacity and serve mechanics are independent of each another, and should be addressed separately.

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.