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The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. A number of social and cognitive abnormalities have been documented in these children as they reach young adulthood. However, little is known about the mechanisms underlying developmental effects of prenatal opioid exposure. Microglia, the resident immune cells of the brain, respond to acute opioid exposure in adulthood. Moreover, microglia are known to sculpt neural circuits during healthy development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors (D1R) in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood in rats. This microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. However, virtually nothing is known as to whether this developmental program is altered by prenatal exposure to opioids. Here, we show in rats that maternal oxycodone self-administration during pregnancy leads to reduced adolescent microglial phagocytosis of D1R and subsequently higher D1R density within the NAc in adult male, but not female, offspring. Finally, we show that prenatal opioid exposure abolishes the extinction of oxycodone-conditioned place preference in these male offspring. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to long-term changes in neural systems and behavior.HighlightsPrenatal opioid exposure decreases offspring viability and body weight in males and femalesPrenatal opioid exposure decreases microglial phagocytosis of D1R in the nucleus accumbens in males onlyPrenatal opioid exposure increases nucleus accumbens dopamine D1 receptor expression in males but not femalesAdult males fail to extinguish oxycodone-conditioned place preference following prenatal oxycodone exposure

Imaging technologies such as positron emission tomography (PET) and magnetic resonance imaging (MRI) present unparalleled opportunities to investigate the neural basis of autism spectrum disorder (ASD). However, challenges such as deficits in social interaction, anxiety around new experiences, impaired language abilities, and hypersensitivity to sensory stimuli make participating in neuroimaging studies challenging for individuals with ASD. In this commentary, we describe the existent training protocols for preparing individuals with ASD for PET/MRI scans and our own experience developing a training protocol to facilitate the inclusion of low-functioning adults with ASD in PET-MRI studies. We hope to raise awareness of the need for more information exchange between research groups about lessons learned in this context in order to include the entire disease spectrum in neuroimaging studies.

Melanocortin-2 receptor accessory protein (MRAP) has an unusual dual topology and influences the expression, localisation, signalling and internalisation of the melanocortin receptor 2 (MC(2)); the adrenocorticotropic hormone (ACTH) receptor. Mutations in MRAP are associated with familial glucocorticoid deficiency type-2 and evidence is emerging of the importance of MRAP in adrenal development and ACTH signalling. Human MRAP has two functional splice variants: MRAP-α and MRAP-β, unlike MRAP-β, MRAP-α has little expression in brain but is highly expressed in ovary. MRAP2, identified through whole human genome sequence analysis, has approximately 40% sequence homology to MRAP. MRAP2 facilitates MC2 localisation to the cell surface but not ACTH signalling. MRAP and MRAP2 have been found to regulate the surface expression and signalling of all melanocortin receptors (MC(1–5)). Additionally, MRAP2 moderates the signalling of the G-protein coupled receptors (GCPRs): orexin, prokineticin and GHSR1a; the ghrelin receptor. Whilst MRAP appears to be mainly involved in glucocorticoid synthesis, an important role is emerging for MRAP2 in regulating appetite and energy homeostasis. Transgenic models indicate the importance of MRAP in adrenal gland formation. Like MC3R and MC4R knockout mice, MRAP2 knockout mice have an obese phenotype. In vitro studies indicate that MRAP2 enhances the MC3 and MC4 response to the agonist αMSH, which, like ACTH, is produced through precursor polypeptide proopiomelanocortin (POMC) cleavage. Analysis of cohorts of individuals with obesity have revealed several MRAP2 genetic variants with loss of function mutations which are causative of monogenic hyperphagic obesity with hyperglycaemia and hypertension. MRAP2 may also be associated with female infertility. This review summarises current knowledge of MRAP and MRAP2, their influence on GPCR signalling, and focusses on pathophysiology, particularly familial glucocorticoid deficiency type-2 and obesity.

Home blood pressure monitors are widely used by consumers yet cardiovascular health may be better defined by pulse-wave velocity (PWV). So far, the Withings Body Cardio scale is the only consumer device that has been designed to measure PWV and body composition, including fat mass (FM) and fat-free mass (FFM), in the home setting. While one study has demonstrated that this device meets the acceptable accuracy standards of the ARTERY Society, no study has accounted for the gravitational effect of standing on a scale on aortic-leg PWV. Purpose: The purpose of this study was to assess the accuracy of PWV and body composition as determined by the Body Cardio scale. Methods: Measurements of PWV and body composition in healthy, young males and females (n = 20) using the Body Cardio device were compared to PWV assessed by applanation tonometry (SphygmoCor) and body composition analysis determined by air displacement plethysmography (Bod Pod). Bland&ndash, Altman analysis and mean absolute percent error (MAPE) were used to assess accuracy. Results: Data are reported as the mean bias (95% confidence interval). The Body Cardio overestimated PWV by 0.68 m/s (&minus, 0.16, 1.51) and FM by 2.91 kg (&minus, 2.91, 8.73). Body Cardio PWV and FM estimations had a MAPE of 9.7% and 25.8%, respectively. The Body Cardio underestimated body mass (BM) and FFM by 0.11 kg (&minus, 0.41, 0.18) and 2.87 kg (&minus, 9.04, 3.30), respectively. Body Cardio BM and FFM estimations had a MAPE of 0.15% and 5.6%, respectively. Conclusions: The Body Cardio scale provides accurate measures of BM and PWV, however, it should be used cautiously for measures of FM and FFM.

Key Clinical Message Stridor is a symptom with a number of causes, usually identified through careful history taking and examination. When the cause is unclear, as in our case, consider investigations such as blood tests, biopsy, and imaging. We discuss a rare diagnosis of plasma cell mucositis, treated with some success by steroids.

In the brain, the µ-opioid receptor (MOR) is involved in reward-seeking behaviors and plays a pivotal role in the mediation of opioid use disorders. Furthermore, reward-seeking behaviors and susceptibility to opioid addiction are particularly evident during the juvenile period, with a higher incidence of opioid use in males and higher sensitivity to opioids in females. Despite these age and sex differences in MOR-mediated behaviors, little is known regarding potential age and sex differences in the expression of MORs in the brain. Here, we used receptor autoradiography to compare MOR binding densities between juvenile and adult male and female rats. Age differences were found in MOR binding density in 12 out of 33 brain regions analyzed, with 11 regions showing higher MOR binding density in juveniles than in adults. These include the lateral septum, as well as sub-regions of the bed nucleus of the stria terminalis, hippocampus, and thalamus. Sex differences in MOR binding density were observed in only two brain regions, namely, the lateral septum (higher in males) and the posterior cortical nucleus of the amygdala (higher in females). Overall, these findings provide an important foundation for the generation of hypotheses regarding differential functional roles of MOR activation in juveniles versus adults. Specifically, we discuss the possibility that higher MOR binding densities in juveniles may allow for higher MOR activation, which could facilitate behaviors that are heightened during the juvenile period, such as reward and drug-seeking behaviors.

Exploration of novel environments, stimuli, and conspecifics is highly adaptive during the juvenile period, as individuals transition from immaturity to adulthood. We recently showed that juvenile rats prefer to interact with a novel individual over a familiar cage mate. However, the neural mechanisms underlying this juvenile social novelty-seeking behavior remain largely unknown. One potential candidate is the oxytocin (OXT) system, given its involvement in various motivated social behaviors. Here, we show that administration of the specific oxytocin receptor antagonist desGly-NH2,d(CH2)5-[Tyr(Me)2,Thr4]OVT reduces social novelty seeking-behavior in juvenile male rats when injected into the nucleus accumbens (10ng/0.5μl/side). The same drug dose was ineffective at altering social novelty-seeking behavior when administered into the lateral septum or basolateral amygdala. These results are the first to suggest the involvement of the OXT system in the nucleus accumbens in the regulation of juvenile social novelty-seeking behavior.

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for a variety of primary immunodeficiency disorders (PIDs). Patients with PID have high rates of pulmonary disease from infections and immune-mediated lung damage, and post-HSCT pulmonary complications account for considerable morbidity and mortality. It is unknown whether pre-HSCT pulmonary disease places PID patients at higher risk for post-HSCT complications. We hypothesize that PID patients with pre-HSCT pulmonary disease have higher risk of transplant-related mortality (TRM), more pulmonary complications, and lower overall survival (OS) compared to PID patients without pre-HSCT pulmonary disease. Objectives The primary aim of this study is to compare TRM in PID patients with and without pre-HSCT pulmonary disease. Secondary aims of the study are to compare OS, incidence of non-infectious and infectious pulmonary disease post-HSCT, ICU transfer for any cause, incidence of acute or chronic GVHD, and immune reconstitution. Methods This is a single center, retrospective, chart review. All pediatric patients (ages 0-18 years) who underwent allogeneic HSCT for a diagnosis of a PID at Boston Children's Hospital from January 2007-June 2018 (n=115) were included in the analysis. We defined non-infectious pulmonary disease as either functional lung impairment based on pulmonary function tests (PFTs), radiographic evidence of pulmonary disease, or documentation of a specific pulmonary diagnosis. We defined infectious pulmonary disease as either viral, bacterial, fungal or other infection in conjunction with positive radiographic and/or bronch/BAL findings. Results Within our cohort, the most common PIDs were SCID (n=28), DOCK8 deficiency (n=16), Wiskott-Aldrich syndrome (n=15), and chronic granulomatous disease (n=9). Of the 115 patients, 54 (47%) had a pre-HSCT diagnosis of pulmonary disease. Pulmonary infection (n=30) and bronchiectasis (n=11) were the most common diagnoses (Fig. 1A). Compared to patients without pre-HSCT lung disease, patients with pre-HSCT lung disease had higher numbers of pulmonary complications after HSCT, such as the need for non-invasive or mechanical ventilation (23 of 54 patients [43%] vs. 12 of 61 patients [20%]) (Fig. 1B). Amongst patients with pre-HSCT lung disease, 1-year survival was 81% compared with 92% in patients without pre-HSCT lung disease. Overall survival was 76% at a median follow up time of 1.6 years versus 89% at a median follow up of 2.7 years in patients with and without pre-HSCT lung disease, respectively (censored logrank p = 0.05) (Fig. 2). Conclusion Within our single center study, PID patients with pre-HSCT lung disease had a trend towards more post-HSCT lung complications and lower OS compared to PID patients without pre-HSCT lung disease. Pulmonary risk factors should be carefully considered in PID patients prior to HSCT.

A 17-year-old Caucasian male presented to ENT with angular stomatitis, oral ulceration and cervical lymphadenopathy. Over the subsequent 18 months he developed recurrent upper respiratory tract infections, pyrexia of unknown origin, oral ulceration and maxillary sinus osteomyelitis. Extensive investigation ensued from various specialties. Positive investigations included a mild but persistently elevated serum Epstein-Barr virus PCR; however, no unifying diagnosis was elicited. It is noteworthy that a significant factor contributing to a delay in his diagnosis was poor compliance with invasive investigations. Ultimately, deteriorating liver function prompted liver biopsy which confirmed a diagnosis of chronic active Epstein-Barr virus infection (CAEBV). This enabled referral for curative treatment in the form of a stem cell transplant. CAEBV is extremely rare in Western countries. Due to fatal complications early diagnosis is critical for successful treatment. Our case highlights the need for regular clinical re-evaluation and a comprehensive multispecialty approach in such cases.

The development of more accurate and sensitive diagnostic techniques is a key factor in efforts to improve cancer survival rates. The technique of infrared aperture fibre scanning near-field optical microscopy (IR-SNOM), together with radiation from the infrared free-electron laser (IR-FEL) on ALICE at Daresbury Laboratory (UK), has been used to obtain IR images of a crypt-like feature and the surrounding tissue; the tissue was taken from a patient with oesophageal adenocarcinoma and with a history of Barrett's oesophagus. We have shown that the DNA signal is enhanced relative to other contributions in the region of the crypt, and the glycoprotein signal shows a less pronounced increase in the region of the crypt. The Amide II signal is found to be anti-correlated with the DNA and glycoprotein profiles. The absorbance of the Amide II signal is found to differ for three different types of cancer tissue. High-resolution IR images of the crypt reveal additional structure that would not be resolved in diffraction-limited techniques.

Aim To test the hypothesis that a ‘basal plus’ regimenadding once-daily main-meal fast-acting insulin to basal insulin once dailywould be non-inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction. Methods This open-label trial enrolled adults to an 8- or 12-week run-in period, during which oral therapies except metformin were stopped and insulin glargine dose was titrated. Those with fasting glucose 7% (53 mmol/mol) were randomized to insulin glargine/glulisine once daily (n = 170) or insulin aspart/aspart protamine 30/70 twice daily (n = 165) for 24 weeks, with dose titration to glucose targets using standardized algorithms. Results For HbA1c, the basal plus regimen was non-inferior to biphasic insulin (least squares mean difference, 0.21%, upper 97.5% confidence limit 0.38%) meeting the predefined non-inferiority margin of 0.4%. Treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version and Insulin Treatment Satisfaction Questionnaire total scores) significantly favoured basal plus. No difference was observed between the basal plus and the biphasic insulin groups in responders (HbA1c

Hypertension is associated with endothelial dysfunction and vascular remodeling. Objective: To assess effects of antihypertensive pharmacotherapy on eNOS-and iNOS-dependent mechanisms and maximal vasodilator capacity in the cutaneous microvasculature. Methods: Intradermal microdialysis fibers were placed in 15 normotensive (SBP 111±2 mm Hg), 12 unmedicated hypertensive (SBP 142±2 mm Hg), and 12 medicated hypertensive (SBP 120±2 mm Hg) subjects. Treatments were control, iNOS-inhibited (1400w), and NOS-inhibited (l-NAME). Red cell flux, measured during local heating (42°C) and ACh dose-response protocols, was normalized to CVC (flux MAP-1) and a percentage of maximal vasodilation (%CVCmax). Results: Compared to normotensives, ACh-mediated vasodilation was attenuated in the hypertensive (P

Background The Strain Index (SI) has been developed to evaluate the risk for developing a distal upper extremity disorder. The objective of this study is to determine if the SI predicts incidence cases of work-related lateral, medial, or any epicondylities (LEPI, MEPI, and EPI). Methods Six hundred seven workers were followed for up to 3.5 years, 70 developed EPI on the dominant side (44 LEPI, 13 MEPI, and 13 both). Survival analyses were conducted adjusting for demographic, psychosocial, and work organizational factors, with the SI as time-dependent variable. Results High exposure (SI > 5), older age, and self-perceived poor general health were associated with incidence of LEPI and EPI, but not MEPI. There was a significant relationship between higher scores of SI and LEPI, hazard ratio (HR) 2.00 (95% CI 1.04–3.87) for SI 5.1–12, HR 2.12 (95% CI 1.11–4.05) for SI > 12. Conclusions The SI can effectively identify jobs with increased risk of developing incidence of LEPI. Am. J. Ind. Med. 57:1319–1330, 2014. © 2014 Wiley Periodicals, Inc.

This is a non-final version of an article published in final form in SMITH, C.J. and HAVENITH, G., 2018. Body sweat mapping of untrained males during exercise-induced hyperthermia: 2506 Board #3 June 1 100 PM - 300 PM. Medicine & Science in Sports & Exercise, 50 (5S), pp.620-621.

Vasopressin (AVP) and oxytocin (OXT) regulate social behavior by binding to their canonical receptors, the vasopressin V1a receptor (V1aR) and oxytocin receptor (OTR), respectively. Recent studies suggest that these neuropeptides may also signal via each other's receptors. The extent to which such cross-system signaling occurs likely depends on anatomical overlap between AVP/OXT fibers and V1aR/OTR expression. By comparing AVP/OXT fiber densities with V1aR/OTR binding densities throughout the rat social behavior neural network (SBNN), we propose the potential for cross-system signaling in four regions: the medial amygdala (MeA), bed nucleus of the stria terminalis (BNSTp), medial preoptic area, and periaqueductal grey. We also discuss possible implications of corresponding sex (higher in males versus females) and age (higher in adults versus juveniles) differences in AVP fiber and OTR binding densities in the MeA and BNSTp. Overall, this review reveals the need to unravel the consequences of potential cross-system signaling between AVP and OXT systems in the SBNN for the regulation of social behavior.

Autism Spectrum Disorders (ASDs) are a collection of complex neurodevelopmental disorders characterized by repetitive behavior and alterations in social interaction/communication. ASD occurs in 1 in 68 children in the US, with a strong sex bias in prevalence ( ∼ 4 males affected to every 1 female). Multiple reports have revealed pervasive immune and mitochondrial abnormalities in ASD patients. Increasing evidence suggests that mitochondrial function is inhibited during proinflammatory microglial activation, although no sex differences remain underexplored. Postmortem analyses of brains from children with ASD revealed significant decreases in expression of mitochondrial electron transport chain (ETC) subunits; however, analyses did not distinguish between cell type or sex. In an early-life immune activation (lipopolysaccharide;LPS) model of ASD, we isolated microglia from prefrontal cortex of PN30 mice. By PCR array, we found that ∼ 96% of mitochondrial ETC genes were strongly diminished by LPS in male microglia, while only ∼ 6% were similarly decreased in females, suggesting that reduced mitochondrial function may be implicated in microglial activation, particularly in males. We show that early-life LPS results in decreased social exploration in both males and females at PN15, but only increased latency to enter stranger bedding in male mice. By PN60, early-life LPS treatment resulted in decreased sociability and social novelty seeking in males only. These data indicate sex-biased deficits in social interaction and anxiety that are related to clinical manifestations of ASD.

This fit and well woman in her 40s presented to A+E with a foreign body throat sensation and dysphagia after swallowing her analgesic tablets in the middle of the night. She was reviewed by the ear, nose and throat team and at that stage she was tolerating fluids, had no airway difficulties and

Regional variation in sweating over the human body is widely recognized yet variation in vasomotor responses and mechanisms causing this variation remain unclear. This study aimed to explore the relation between regional sweating rates (RSR) and skin blood flow (SkBF) responses to thermal and pharmacological stimuli in young, healthy subjects. In nine subjects (23 ± 3 yr), intradermal microdialysis (MD) probes were inserted into the ventral forearm, abdomen, thigh, and lower back and perfused with lactated Ringer solution. RSR over each MD membrane were measured using ventilated capsules with a laser Doppler probe housed in each capsule for measurement of red cell flux (laser Doppler flux, LDF) as an index of SkBF. Subjects completed a whole body heating protocol to 1°C rise in oral temperature and an acetylcholine dose response (ACh 1 × 10−7-0.1 M; mean skin temperature 34°C). Maximal LDF were obtained at the end of both protocols (50 mM sodium nitroprusside).During heating RSR varied among sites ( P < 0.0001) and was greater on the back versus other sites ( P < 0.05), but LDF was similar between sites ( P = 0.343). RSR and SkBF showed a strong relation during initial (arm: r = 0.77 ± 0.09, thigh: r = 0.81 ± 0.08, abdomen: r = 0.89 ± 0.04, back: r = 0.86 ± 0.04) but not latter stages of heating. No differences in RSR ( P = 0.160) or SkBF (LDF, P = 0.841) were observed between sites during ACh perfusion. Taken together, these data suggest that increases in SkBF are necessary to initiate and increase sweating, but further rises in RSR are not fully dependent on SkBF in a dose-response manner. Furthermore, RSR cannot be explained by cholinergic sensitivity or variation in SkBF.

Angioleiomyomas are a benign group of tumours rarely documented in the head and neck region. We present a case of a 47-year-old man attending the ear, nose and throat outpatient clinic, with a history of hoarseness over many years. Investigation revealed a left-sided subglottic lesion. He underwent microlaryngoscopy and biopsy, and the lesion was sent for histological analysis. Postoperatively, the patient began to expectorate fresh red blood that continued for several hours, requiring surgical intervention. Haemostatic control was achieved and a tracheostomy was sited for airway protection. Histopathology identified angioleiomyoma as the cause of his symptoms. Following multidisciplinary team discussion, this was managed with injection of bleomycin and subsequent surgical excision. This case is a reminder that subglottic lesions are often vascular in nature, and should be investigated with imaging and angiography prior to surgery, to avoid complications.

Essential hypertension is a proinflammatory, proconstrictor disease coinciding with endothelial dysfunction and inward vessel remodeling. Using the skin circulation, our aim was to determine whether inducible NO synthase (iNOS) upregulation attenuates NO-dependent cutaneous vasodilation in hypertensive humans. We hypothesized that, with hypertension, localized iNOS inhibition would restore vasodilation in response to NO-dependent stimuli, and iNOS expression would be increased and phosphorylated vasodilator-stimulated phosphoprotein would be decreased. For, in vivo protocols, 4 intradermal microdialysis fibers were placed in 9 hypertensive and 10 normotensive men and women (systolic blood pressure: 146±4 versus 113±2 mm Hg; P N ω - propyl - l -arginine), and nonselective NOS inhibited ( N G -nitro- l -arginine methyl ester). Cutaneous vascular conductance was calculated (percentage of sodium nitroprusside) during standardized local heating (42°C) and acetylcholine dose-response protocols (0.01, 0.10, 1.00, 5.00, 10.00, 50.00, 100.00 mmol/L). The NO-dependent local heating response was attenuated at control (95±2% versus 76±2% cutaneous vascular conductance; P P P P P P =0.006) and phosphorylated vasodilator-stimulated phosphoprotein was decreased in skin from hypertensive humans ( P =0.04). These data suggest that iNOS is upregulated in essential hypertensive humans and contributes to reduced NO-dependent cutaneous vasodilation.

The pH of the solution is shown to significantly effect the reflection anisotropy spectroscopy (RAS) profiles of adenine adsorbed at Au(110)/electrolyte interfaces. At pH 12.8 the net adsorption is very weak due the formation of negative adenine ions in solution. The sensitivity of the RAS profiles to the pH of the solution is probably due to a change in the geometry of the adsorbed molecules caused by a disruption of the base stacking configuration that is adopted when adenine is adsorbed from solutions at pH 7.1.

OBJECTIVE: The aim of this study was to assess prevalence, incidence, and persistence of carpal tunnel syndrome (CTS) and associated symptoms over a one-year period in a working population. METHODS: We conducted a one-year prospective study of 418 active workers in 12 worksites. Detailed health interviews, psychosocial questionnaires, and electrophysiological studies [ie, nerve conduction velocity (NCV) tests] were conducted at baseline and one-year follow-up. Individual-observed exposure assessments of wrist posture, hand activity, and hand forces were conducted. RESULTS: Prevalence of CTS cases at baseline was 10.8% [95% confidence interval (95% CI) 7.8–13.7%] on the dominant side and 6.0% (95% CI 3.7–87.3%) on the non-dominant side; CTS symptoms were 14.1% (95% CI 10.8–17.5%) and 11.0% (95% CI 8.0–14.0%), respectively. Incidence of CTS cases were 7.5% (95% CI 4.8–10.2%) and 5.6% (95% CI 3.3–7.9%), respectively. Higher proportions of subjects with current symptoms or positive electrophysiological test findings at baseline became CTS cases at one year compared to those with neither (28.6% and 13.9%, respectively, versus 0.5%). One-year persistence of CTS case status was 44.4% (95% CI 29.9–59.0%) for the dominant hand and 52.0% (95% CI 32.4–71.6) for non-dominant hand. There were significant differences at baseline between asymptomatic subjects and CTS cases with respect to higher job demands (P=0.027), lower job satisfaction (P=0.036), lower general health (P=0.0009), higher exposure to vibrating hand tool use (P=0.039), and greater time using a forceful power grip (P=0.035) among cases. CONCLUSIONS: CTS symptoms more than positive NCV test results alone appear to predict CTS at one year. Persistence of CTS at one year is high.

Background Evidence regarding the unequal burden of occupational injuries between workers employed by temporary agencies and those in standard employment arrangements is unclear. Studies range from no significant differences in risk to substantial increased risk for temporary workers. The purpose of this study is to compare the workers' compensation experience of a large cohort of temporary agency employed workers with those in standard forms of employment. Methods Washington State Fund workers' compensation data were obtained for claims with injury dates from January 1, 2003 to June 30, 2006, resulting in 342,540 accepted claims. General descriptive statistics, injury rates (per 10,000 FTE), and rate ratios (temp agency/standard employer) were computed by injury type and industry. Results Temporary agency employed workers had higher rates of injury for all injury types, and higher median time loss (40 vs. 27 days) but lower time loss costs (median $1,224 vs. $1,914, P

Background Lateral epicondylitis is a common work-related musculoskeletal disorder. The objective of this study was to identify risk factors associated with lateral epicondylitis among active workers. Methods Seven-hundred thirty-three workers in 12 Washington worksites participated in structured interviews, physical examinations, and individual exposure assessments of biomechanical and psychosocial factors. Multivariable logistic modeling was used. Results Thirty-eight subjects (5.2%) had lateral epicondylitis. Age (36–50 years-old), being female, and low social support at work were significant risk factors. Frequency of forceful exertion (≥5 vs.

Background Hand symptom diagrams (HSDs) for rating the distribution of paraesthesias are proposed for use in epidemiological studies of carpal tunnel syndrome (CTS). Aim To assess the validity of HSDs in a working population of manufacturing and service workers participating in a prospective study of musculoskeletal disorders. Methods Assessment of each subject involved completing a HSD, a heath assessment and electrodiagnostic studies (EDSs). HSDs were rated for CTS blinded to the health assessment and EDS results. The validity assessments of HSD used EDS as the sole confirmatory standard for CTS. Results A total of 733 subjects (65% of those eligible) participated in the study and 720 underwent EDSs. Dominant hand prevalence of a positive HSD and delayed nerve conduction studies in this working population was 9.2 per 100 workers. The sensitivity of a positive HSD for all workers was 0.28. By restricting the population to those workers with any current hand symptoms or to any worker with neuropathic hand symptoms, the sensitivities of HSD improved to 0.61 and 0.79, respectively. The positive predictive value of a HSD, with our study prevalence, was 0.48. Conclusions The HSD classification schema has poor validity when applied to a general working population but improves when applied to workers with current neuropathic symptoms. The high number of false-negative HSDs in the general study population is most likely to be due to the inadequacies of using EDS as the confirmatory test. With a low prevalence of CTS, the positive predictive value for HSDs is poor.

The purpose of this article was to assess validity of the regional Disabilities of Arm, Shoulder, and Hand (QuickDASH) and Short-Form 12 (SF-12) for surveillance purpose. We compared the predictive, discriminate, and concurrent validity of the QuickDASH and SF-12 among 231 workers with specific clinical diagnoses of neck or upper extremity musculoskeletal disorders (UEMSDs) and 175 workers with symptoms only. Compared to those with symptoms only, the odds of being any neck or UEMSD case were 1.45 (95% confidence interval [95% CI]: 1.24-1.70) and 0.66 (95% CI: 0.48-0.91) with every 10-point increase in QuickDASH disability and physical component scale (PCS-12) scores, respectively. The clinical cases had significantly higher QuickDASH disability (23.0 vs. 14.3, p

C-reactive protein (CRP) has received much attention as a cardiovascular risk factor and has been recommended to be used in screening to assist in predicting the occurrence of cardiovascular disorders. There are numerous association studies documenting changes in circulating CRP concentrations, there are, however, fewer studies providing evidence that CRP mediates the progression of cardiovascular pathologies. Elucidating the potential mechanisms for CRP has been confounded by recent reports that contaminants of CRP are partially responsible for observed effects. In this review the use of CRP as a tool to predict cardiovascular disorders will be discussed alongside a more recently described cardiovascular risk factor asymmetric dimethylarginine (ADMA). An endogenously occurring nitric oxide synthase inhibitor, ADMA, is formed by the action of protein arginine methyltransferases and subsequent proteolysis and it is metabolised in vivo by the dimethylarginine dimethylaminohydrolases (DDAH). The evidence available documenting the effects of CRP and ADMA, the regulatory mechanisms and the genetic influences, will be discussed in order to determine whether CRP and ADMA are mediators in the progression of cardiovascular disorders or merely useful biomarkers.

Objectives This study assessed the prevalence, incidence, and persistence of nontraumatic rotator cuff tendinitis and shoulder symptoms over a 1-year period in a working population and the predictive value of symptoms and physical findings. Methods A 1-year prospective study of 436 active workers was conducted at 12 different worksites. Detailed health interviews, psychosocial questionnaires, and physical examinations were conducted at baseline and again after 1 year, with shorter evaluations at 4 and 8 months. Individual observed exposure assessment of shoulder posture, arm–hand activity, and hand forces was conducted. Results The prevalence of rotator cuff tendinitis at baseline was 7.6% [95% confidence interval (95% CI 5.1–10.1%)] for the right and 4.8% (95% CI 3.0–7.0%) for the left, compared with shoulder symptoms of 18.6% (95% CI 14.9–22.3%) (right) and 11.2% (95% CI 8.2–14.2%) (left). The incidence of rotator cuff tendinitis was 5.5% (95% CI 2.8–6.8%) and 2.9% (95% CI 1.0–3.8%), respectively. Higher proportions of participants with current symptoms or physical findings at baseline became clinical cases after 1 year than those without symptoms or findings. The 1-year persistence of clinical case status was 31.3% (95% CI 26.9–35.7%) (right) and 31.6% (95% CI 27.2–36.0%) (left). There were significant differences at baseline between the asymptomatic participants and the clinical cases with respect to physical health on the 12-item Short-form Health Survey (P=0.0002), the perception of general health (P=0.0027), and the frequency of high hand force exposure (P=0.0177). Conclusions Considerable movement occurs between different stages of shoulder problems. Symptoms and physical findings alone appear to predict clinical case status within 1 year. Frequent follow-up is necessary to capture changes in health and exposure status in prospective studies.

Asymmetric dimethylarginine (ADMA) is an endogenously occurring methylarginine that inhibits nitric oxide synthesis. Plasma levels of methylarginines increase in renal failure and certain cardiovascular pathologies, and in patients with end stage renal failure the level of ADMA predicts the risk of cardiovascular events and overall mortality. The object of this review is to describe the mechanisms of ADMA synthesis, metabolism and uptake and to outline techniques for measuring ADMA and the pathological states in which ADMA levels are altered.

Objectives: To evaluate the diet of 16–18-y-old boys and girls with particular reference to intakes of nutrients believed to affect bone health and dietary acid–base balance. Design: A 7-day food diary was completed between the months of October and December. Setting: Cambridge, UK Subjects: A total of 111 boys and 101 girls aged 16–18 y who were recruited into the Cambridge Bone Studies. Main outcome measures: Mean daily intakes of foods and selected nutrients (protein, calcium, phosphorus, magnesium, potassium, vitamins C and K) were calculated. Two estimates of acid–base balance were calculated from the diet using the formulae of Remer (net acid excretion, estimated indirectly; NAEind) and Frassetto (protein/potassium ratio). Results: Mean calcium and phosphorus intakes were above the UK Reference Nutrient intake (RNI). In all, 39% of the boys and 36% of the girls had vitamin K intakes lower than 1 μg/kg body weight/day. Calcium intake was positively correlated with all other nutrients except vitamins C and K. Boys had a significantly higher estimated net acid excretion (NAEind) than girls (P

Key Clinical Message Lingual tonsillar hypertrophy is an unusual presentation of voice change. If managed incorrectly this group of patients has the potential to deteriorate significantly causing airway obstruction and potentially death.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH activity. We modified DDAH activity in cells and measured the changes in ADMA levels, morphological phenotypes on Matrigel, and expression of vascular endothelial growth factor (VEGF). DDAH over-expressing ECV304 cells secreted less ADMA and when grown on Matrigel had enhanced tube formation compared to untransfected cells. VEGF mRNA levels were 2.1-fold higher in both ECV304 and murine endothelial cells (sEnd.1) over-expressing DDAH. In addition the DDAH inhibitor, S-2-amino-4(3-methylguanidino)butanoic acid (4124W 1mM), markedly reduced human umbilical vein endothelial cell tube formation in vitro. We have found that upregulating DDAH activity lowers ADMA levels, increases the levels of VEGF mRNA in endothelial cells, and enhances tube formation in an in vitro model, whilst blockade of DDAH reduces tube formation.

This paper describes a battery of physical exposure assessment methods used in a large prospective upper extremity musculoskeletal disorders study. Different from some previous prospective studies, this study collects health and physical exposure data for each study subject rather than at a group level. Subjects are recruited from different job categories based on their hand activity exposure categories. Multiple exposure assessment methods are used to measure job physical exposures such as force, repetition, and work posture. This will allow us to compare the sensitivity of different exposure assessment methods in predicting the risk for upper extremity musculoskeletal disorders. Procedures have also been taken to monitor inter-observer reliability for some observational analyses. During the first year of the study, baseline exposure measurements have been collected from 607 volunteers at 11 different worksites. Follow-up measurements have also been collected in these worksites. Whenever a participant has a significant job change, a new exposure assessment is conducted at the new job. This paper will primarily discuss the various exposure assessment methods used in this study, and use some preliminary results to demonstrate some of the data reduction methods.

Background The use of fibrin sealant in the management of pilonidal sinus disease has not previously been described in children. We present our experience of primary pit excision and use of fibrin sealant (PEF) and compare outcomes with lateralising flap procedures (LFP). Methods A single centre retrospective case note review of all children who had undergone a definitive procedure for pilonidal sinus from August 2006 to Dec 2013 was performed using data expressed as median (range) and compared using Fisher’s exact test. P Results Forty-one children were identified having undergone 49 procedures, with median age 15 (12–16 years) and follow up 32 (8–92) months. Groups were comparable for disease severity. Ten children underwent primary PEF and twenty-six LFP. Two children had recurrence following primary PEF and had repeat PEF which was curative. Overall recurrence rates following PEF procedure were comparable to LFP (17% vs 21%; P = 1.0). There were no wound dehiscences in the PEF group and one wound infection. There was one wound dehiscence and one wound infection in the LFP group. Median operative time for PEF was lower than LFP (20 vs 60 min, P = 0.001). 83% of PEF procedures were performed as day cases. One child was lost to follow up, and two children progressed to adult services. Conclusions We recommend PEF in children with pilonidal sinus disease as primary treatment and for recurrence. PEF has comparable recurrence and wound infection rates to LFPs, is performed as day case, has shorter anaesthetic times, and the risk of wound dehiscence is avoided.

We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me(2))AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5-[Tyr(Me)(2),Thr(4)]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.

Objective: The objective of this prospective study is to investigate the exposure–response relationships between various workplace physical exposures of force, repetition, and their combination assessed at an individual level with lateral epicondylitis (LE). Background: Workplace upper extremity musculoskeletal disorders (UEMSDs) are prevalent, disabling, and expensive. LE is one of the major UEMSDs in active workers. Method: We used detailed health history, symptoms, and physical examination for identifying incidence and detailed exposure assessment to capture work tasks of each worker and to measure quantitative mechanical workload. We used counting process style input of proportional hazards regression for modeling cumulative incidence that accounts for changed exposure estimates during the follow-up period when respondents change jobs. Results: The incidence rate of LE on the dominant side was 4.91 per 100 person-years. Adjusted for age and gender, the combined effect of forearm pronation ≥45° for ≥40% of time and time spent with forceful exertion, including any power grip (hazard ratio [HR] = 2.8, 95% confidence interval [CI] = [1.35–5.77]), lifting for ≥3% of time (HR = 2.50, 95% CI = [1.19–5.24]), and duty cycle for forceful exertion for ≥10% (HR = 2.25, 95% CI = [1.09–4.66]), were significant predictors of dominant side LE, whereas neither the awkward posture nor the forceful exertion alone was significant. Older workers with jobs requiring a high percentage of time working with force in combination with awkward postures of forearm were more likely to predict LE. Conclusion: This study shows the evidence of the etiologic role of strenuous manual tasks in the occurrence of LE.

Melanocortin receptors (MCS, MC1–MC5) are GPCRs, activated with different affinities by the melanocortin peptides (?-, ?-, ?-MSH and ACTH). They are widely distributed throughout the body displaying a multitude of actions however their role in reproductive physiology is unclear. Previously, we have shown a reduction of pituitary hormone content and abnormalities in testes morphology in male MC3 null mice. The aim of this study was to characterise MCS expression in the male mouse reproductive axis and to investigate the effects of MCS agonists/antagonists on in vitro testicular testosterone production (TP). MCS expression patterns were determined in mRNAs from hypothalami, pituitaries and testes of Balb/c and C57BL/6 male mice by two-step reverse transcriptase (RT) - quantitative (q) PCR and analysed using qBaseplus. To examine the functions of MCS in gonads, testes of Balb/c and C57BL/6 mice were hemi-sected and incubated with the potent MC3 and, to a lesser extent, MC4 agonist ([D-TRP8]-?2-MSH; 0.3–10 ?g/ml) in the presence or absence of hCG (50 mIU/ml) and/or a MC3/MC4 antagonist and MC1/MC5 agonist (SHU9119; 10 ?g/ml) for 5 h at 35 °C in air. There were no significant differences in the pattern of MCS expression between C57BL/6 and Balb/c. The most abundant MC in the hypothalamus and pituitary appears to be MC3 whilst in the testis it was MC2. TP in C57BL/6 mice is 50% less than in Balb/c: confirming published data that the former mice are hypoandrogenic. Activation of MC3 and MC4 using [D-TRP8]-?2-MSH had no or inhibitory effects on basal TP in Balb/c and C57BL/6, respectively. The same ligand decreased TP in both strains in the presence of hCG. In contrast, SHU9119±hCG increased TP threefold compared to basal levels independently of ligand dose in Balb/c. This study suggests that activation of specific MCS can alter TP however further work is required.

Objectives To identify the treatment patterns and early complication rates in women identified with a genital infection prior to a termination of pregnancy (TOP) and to re-assess our earlier work on contact attendance and treatment. The aim was to refine current prophylactic measures to provide the most efficient and effective way of reducing post-termination complications. Method Six-month retrospective analysis of all women with genital Chlamydia trachomatis or Neisseria gonorrhoeae identified prior to TOP. Data on the timing of positive results and treatment in relation to the TOP were recorded. Clinical signs of pelvic infection and the success of contact tracing and treatment were noted. Results Forty women were identified with infection, 31 (78%) proceeded to TOP; only five were treated adequately in the peri-TOP period. Twenty-six (84%) of the women undergoing TOP attended the genitourinary medicine (GUM) department after the TOP and received antimicrobial therapy where necessary. In total, four women (10%) were untreated. Approximately two thirds of results were reported prior to, or on the day of, the TOP. The majority of TOPs (71%) were carried out at 5 days or less from the initial assessment. Clinical signs of post-TOP pelvic inflammation developed in seven (28%) women with chlamydial infection. Contact tracing was successful in 24 (69%) of the 35 women who attended the GUM department. Conclusion The debate about the best option for the most effective management of women undergoing TOP continues. The options with respect to C. trachomatis include universal prophylaxis, screening and treating as necessary, or a 9belt and braces9 approach of screening all and treating all. Fundamental is the continuation of active contact tracing and GUM remains integral to this.

Background: The role of nutritional influences on bone health remains largely undefined because most studies have focused attention on calcium intake. Objective: We reported previously that intakes of nutrients found in abundance in fruit and vegetables are positively associated with bone health. We examined this finding further by considering axial and peripheral bone mass and markers of bone metabolism. Design: This was a cross-sectional study of 62 healthy women aged 45-55 y. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck and by peripheral quantitative computed tomography at the ultradistal radial total, trabecular, and cortical sites. Bone resorption was calculated by measuring urinary excretion of pyridinoline and deoxypyridinoline and bone formation by measuring serum osteocalcin. Nutrient intakes were assessed by using a validated food-frequency questionnaire; other lifestyle factors were assessed by additional questions. Results: After present energy intake was controlled for, higher intakes of magnesium, potassium, and alcohol were associated with higher total bone mass by Pearson correlation (P < 0.05 to P < 0.005). Femoral neck BMD was higher in women who had consumed high amounts of fruit in their childhood than in women who had consumed medium or low amounts (P < 0.01). In a regression analysis with age, weight, height, menstrual status, and dietary intake entered into the model, magnesium intake accounted for 12.3% of the variation in pyridinoline excretion and 12% of the variation in deoxypyridinoline excretion. Alcohol and potassium intakes accounted for 18.1% of the variation in total forearm bone mass. Conclusion: The BMD results confirm our previous work (but at peripheral bone mass sites), and our findings associating bone resorption with dietary factors provide further evidence of a positive link between fruit and vegetable consumption and bone health.

Essential hypertension (HT) is associated with endothelial dysfunction augmented vasoconstriction (VC) which may be secondary to increased Rho/Rho-Kinase (ROCK)-dependent mechanisms. Our aim was to assess the in vivo magnitude of cutaneous VC to local cooling as a ROCK specific stimulus, and in vitro evaluate ROCK activity in skin from HT humans. Four microdialysis fibers were placed in the forearm of 9 pre- to stage I hypertensive (MAP: 106 ± 3 mmHg) and 11 normotensive (NT; 86 ± 1 mmHg) men and women: Ringers (control), 3 mM fasudil (ROCK inhibited), 5 mM yohimbine + 1 mM proprananol (α- and β-adrenoceptor inhibited; Y + P), Y + P + 3 mM fasudil (ROCK and adrenocepor inhibited). Skin blood flow was measured during local cooling (Tskl 24°C) and ROCK activity in skin biopsy samples was determined with western blot. In vitro phosphorylated myosin phosphatase target subunit 1 (pMYPT-1)/ROCK was increased in HT skin samples (p=0.0018). Functionally, no difference in basal vasomotor tone (Tskl 34°C) was observed between groups (HT: 0.36 ± 0.07 vs. NT: 0.31 ± 0.07 CVC), nor at the control site during local cooling. Pre- to stage 1 hypertensives show greater ROCK-mediated vasoconstriction at early (1–5 min; HT: −0.8±0.2 versus NT: −0.3±0.2 ΔCVC baseline 1; P

Background Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas. Methodology/Findings 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and “other signs/symptoms”). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone. Conclusions These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended. Trial Registration ClinicalTrials.gov; NCT01586169, Author Summary Neglected tropical diseases are co-endemic in many areas of the world. Currently lymphatic filariasis (albendazole+ivermectin) and trachoma (azithromycin) are treated separately. Benefits can be gained from integration of preventive chemotherapy programs in such areas. To assess the safety of this approach, 4 villages in two co-endemic districts in Mali were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). One village was randomly assigned to each treatment in each district. 3011(40.1%) of 7515 eligible individuals in the 4 villages participated in the study. No serious adverse events occurred, and most events were mild in intensity (mainly headache, abdominal pain, and diarrhoea). Overall the number of subjects reporting any event was similar with co-administration compared to standard treatment [18.7% (281/1501) vs. 15.8% (239/1510)]. The overall frequency of adverse events with co-administration was comparable to or lower than published frequencies for ivermectin/albendazole alone. These data suggest that co-administration is safe; however the small number of villages studied and the large differences between them meant that a meaningful estimate of the differences could not be calculated, and further work will be needed before a recommendation can be made.

Childhood abuse is known to have a negative influence on human development. This study expected to find a spiritual attitude of acceptance, as measured by the Ego Grasping Orientation scale, would help mitigate effects of childhood abuse in the realm of spiritual development. Spiritual Experience Index (SEI) scores for 350 religious women were treated as a measure of spiritual maturity. Contrary to expectation, however, the sexually and the physically abused groups with a more accepting attitude scored lower on the SEI than the abused with a more controlling attitude and the nonabused. Implications for spiritual development and well-being are discussed.

The presynaptic source of dopamine in the CA1 field of dorsal hippocampus is uncertain due to an anatomical mismatch between dopaminergic terminals and receptors. We show, in anin vitroslice preparation from C57BL/6 male mice, that a dopamine (DA) D1 receptor (D1R)-mediated enhancement in glutamate synaptic transmission occurs following release of endogenous DA with amphetamine exposure. It is assumed DA is released from terminals innervating from the ventral tegmental area (VTA) even though DA transporter (DAT)-positive fibers are absent in hippocampus, a region with abundant D1Rs. It has been suggested this results from a lack of DAT expression on VTA terminals rather than a lack of these terminals per se. Neither a knockdown of tyrosine hydroxylase (TH) expression in the VTA by THsiRNA, delivered locally, by adeno-associated viral vector, nor localized pharmacological blockade of DAT to prevent amphetamine uptake into DA terminals, has any effect on the D1R synaptic, enhancement response to amphetamine. However, either a decrease in TH expression in the locus ceruleus (LC) or a blockade of the norepinephrine (NE) transporter prevents the DA-mediated response, indicating LC terminals can release both NE and DA. These findings suggest noradrenergic fibers may be the primary source of DA release in hippocampus and corresponding DA-mediated increase in synaptic transmission. Accordingly, these data imply the LC may have a role in DA transmission in the CNS in response to drugs of abuse, and potentially, under physiological conditions.

Interactive video gaming has become ubiquitous in the practice of rehabilitation. The Nintendo Wii is one such system. Interactive gaming can promote intensive task-based therapy in a manner that is motivating for the user. Widespread enthusiasm for consoles and their games prompted us to analyze the games for their rehabilitation elements related to improving balance and mobility for individuals poststroke.The purpose of this article is to provide a game analysis for clinical application and evaluation of the game elements for research on interactive video gaming.Using a team of game players and raters, 5 tables (1 for the Wii Sports and 4 for the Wii Fit) were developed and validated. The tables consist of 3 categories: game description, impairments targeted (strength, endurance, balance, and coordination), and feedback provided (knowledge of performance [KP] and knowledge of results [KR]). Two domain content experts established face validity. Construct validity was performed by 2 therapist-raters who had more than 15 years' clinical experience and postgraduate training in motor learning. Observations about the games including the fidelity of the interfaces, the nature of the feedback, and some of the challenges to adapting the games for rehabilitation are presented.An 80% agreement between raters set as the criterion for establishing the construct validity was met for feedback evaluation. There was 100% agreement on impairment ratings. Games provide a greater amount of KR compared with KP.Given the preponderance of KR, therapists will need to monitor motor performance. Adaptation of interactive video consoles for rehabilitation requires careful evaluation of the games' attributes using relevant rehabilitation construits.

Defining how arginine vasopressin (AVP) acts centrally to regulate homeostasis and behavior is problematic, as AVP is made in multiple nuclei in the hypothalamus (i.e., paraventricular [PVN], supraoptic [SON], and suprachiasmatic [SCN]) and extended amygdala (i.e., bed nucleus of the stria terminalis [BNST] and medial amygdala [MeA]), and these groups of neurons have extensive projections throughout the brain. To understand the function of AVP, it is essential to know the site of origin of various projections. In mice, we used gonadectomy to eliminate gonadal steroid hormone-dependent expression of AVP in the BNST and MeA and electrolytic lesions to eliminate the SCN, effectively eliminating those AVP-immunoreactive projections; we also quantified AVP-immunoreactive fiber density in gonadectomized and sham-operated male and female mice to examine sex differences in AVP innervation. Our results suggest that the BNST/MeA AVP system innervates regions containing major modulatory neurotransmitters (e.g., serotonin and dopamine) and thus may be involved in regulating behavioral state. Furthermore, this system may be biased toward the regulation of male behavior, given the numerous regions in which males have a denser AVP-immunoreactive innervation than females. AVP from the SCN is found in regions important for the regulation of hormone output and behavior. Innervation from the PVN and SON is found in brain regions that likely work in concert with the well-known peripheral AVP actions of controlling homeostasis and stress response; female-biased sex differences in this system may be related to the heightened stress response observed in females.