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Background: Adaptive learning (AL) platforms deliver content personalized to students on the basis of prior knowledge, adjusting content delivery based on individual preferences and differences in knowledge acquisition. This project compared a course developed in an AL platform with one in a traditional learning management system (LMS) only. Method: This pilot of an adaptive graduate nurse educator pathophysiology course was a randomized control group experimental study. Results: Data from Fall 2018 and Spring 2019 semesters showed 86% of the participants ( n = 21) strongly agreed that they learned better using an AL platform. All of the participants ( N = 23) reported increased course engagement, and 86% ( n = 21) reported they would like to take a course using this platform again. Conclusion: This pilot demonstrated a potentially effective way to support students' learning. Students perceived greater engagement with content, reported more effective learning, and expressed interest in taking a course in an AL platform again. [ J Nurs Educ . 2020;59(6):327–330.]

Background Pulmonary function tests (PFTs) are performed routinely to evaluate lung function in patients with cystic fibrosis (CF). Staff at the Cincinnati Children's Hospital Medical Center CF Center observed stress in patients before PFTs. An interdisciplinary quality improvement (QI) team was assembled to address this clinical issue. Methods The Plan-Do-Study-Act method of QI was used to investigate feasibility of assessing stress and offering brief interventions to reduce stress before PFTs. Interventions included listening to music, covering the PFT screen, or doing breathing meditation before PFTs. Patients rated stress levels on a 1 to 5 Likert scale before and after testing. Results Of 75 patient encounters, interventions were trialed in 20. Fifteen patients who tried an intervention reported wanting to use the intervention again (five encounters had missing data); patients reported that the intervention benefited performance on PFTs in eight encounters (40%). The average pre-PFT stress rating for encounters that trialed an intervention was 2.1 and post-PFT rating was 2.0. Average stress pre-PFT and post-PFT ratings were 1.7 and 1.6 respectively, for encounters that did not trial an intervention. Median length of PFT encounter was 15 minutes regardless of whether intervention was trialed. Conclusion Some patients with CF utilized interventions, while many opted out. This QI effort identified feasible outpatient clinic interventions that did not negatively impact clinic flow. Finding ways to reduce stress associated with PFTs could have a meaningful impact on patient performance and emotional well-being for a subset of patients.

In the bone marrow (BM) microenvironment, where breast cancer (BC) disseminated tumour cells (DTCs) can remain dormant for decades, NG2

“Stem-like” TCF1(+) CD8(+) T cells (T(SL)) are necessary for long-term maintenance of T cell responses and the efficacy of immunotherapy but, as tumors contain signals that should drive T-cell terminal-differentiation, how these cells are maintained in tumors remains unclear. In this study, we found that a small number of TCF1(+) tumor-specific CD8(+) T cells were present in lung tumors throughout their development. Yet, most intratumoral T cells differentiated as tumors progressed, corresponding with an immunologic shift in the tumor microenvironment (TME) from “hot” (T cell-inflamed) to “cold” (non-T cell-inflamed). By contrast, most tumor-specific CD8(+) T cells in tumor-draining lymph nodes (dLNs) had functions and gene expression signatures similar to T(SL) from chronic LCMV infection, and this population was stable over time, despite the changes in the TME. dLN T cells were the developmental precursors of, and were clonally related to, their more differentiated intratumoral counterparts. Our data support the hypothesis that dLN T cells are the developmental precursors of the TCF1(+) T cells in tumors which are maintained by continuous migration. Finally, CD8(+) T cells similar to T(SL) were also present in LNs from lung adenocarcinoma patients, suggesting a similar model may be relevant in human disease. Thus, we propose that the dLN T(SL) reservoir has a critical function in sustaining antitumor T cells during tumor development and protecting them from the terminal differentiation that occurs in the TME.

Objective(s) To define the evolving role of integrative surgical management including transplantation for patients gut failure (GF). Methods A total of 500 patients with total parenteral nutrition-dependent catastrophic and chronic GF were referred for surgical intervention particularly transplantation and comprised the study population. With a mean age of 45 ± 17 years, 477 (95%) were adults and 23 (5%) were children. Management strategy was guided by clinical status, splanchnic organ functions, anatomy of residual gut, and cause of GF. Surgery was performed in 462 (92%) patients and 38 (8%) continued medical treatment. Definitive autologous gut reconstruction (AGR) was achievable in 378 (82%), primary transplant in 42 (9%), and AGR followed by transplant in 42 (9%). The 84 transplant recipients received 94 allografts; 67 (71%) liver-free and 27 (29%) liver-contained. The 420 AGR patients received a total of 790 reconstructive and remodeling procedures including primary reconstruction, interposition alimentary-conduits, intestinal/colonic lengthening, and reductive/decompressive surgery. Glucagon-like peptide-2 was used in 17 patients. Results Overall patient survival was 86% at 1-year and 68% at 5-years with restored nutritional autonomy (RNA) in 63% and 78%, respectively. Surgery achieved a 5-year survival of 70% with 82% RNA. AGR achieved better long-term survival and transplantation better (P = 0.03) re-established nutritional autonomy. Both AGR and transplant were cost effective and quality of life better improved after AGR. A model to predict RNA after AGR was developed computing anatomy of reconstructed gut, total parenteral nutrition requirements, cause of GF, and serum bilirubin. Conclusions Surgical integration is an effective management strategy for GF. Further progress is foreseen with the herein-described novel techniques and established RNA predictive model.

Crouzon syndrome is the result of a gain-of-function point mutation in FGFR2. Mimicking the human mutation, a mouse model of Crouzon syndrome (Fgfr2342Y) recapitulates patient deformities, including failed tracheal cartilage segmentation, resulting in a cartilaginous sleeve in the homozygous mutants. We found that the Fgfr2C342Y/C342Y mutants exhibited an increase in chondrocytes prior to segmentation. This increase is due at least in part to over proliferation. Genetic ablation of chondrocytes in the mutant led to restoration of segmentation in the lateral but not central portion of the trachea. These results suggest that in the Fgfr2C342Y/C342Y mutants, increased cartilage cell proliferation precedes and contributes to the disruption of cartilage segmentation in the developing trachea.

Maintaining optimal body condition is an important concern for horse owners and managers as it can affect reproductive efficiency, athletic ability, and overall health of the horse; however, information regarding dietary requirements to maintain or alter BCS in the horse is limited. A recently developed model had high accuracy in predicting the energy required to alter BCS in the horse. However, the model was restricted to sedentary mares, while many horses are subject to physical work. The objective of this study was to expand the scope of that model to include exercising horses by incorporating previously published estimates of exercise energy expenditure and then testing the expanded model. Stock type horses (n = 24) were grouped by initial BCS (3.0 to 6.5) and assigned to treatments of light (L), heavy (H), or no-exercise control (C). Horses were fed according to the model recommendations to increase (I) or decrease (D) two BCS within 60 d. Thus, six treatments were obtained: HD, HI, LD, LI, CD, CI. Mean DE intake Mcal/d for each group was HD = 19.3 ± 0.90, HI = 29 ± 0.84, LD = 13.2 ± 0.54, LI = 23.1 ± 1.39, CD = 12.1 ± 0.79, and CI = 21.9 ± 0.94. BCSs were evaluated by three independent appraisers, days 0 and 60 values were used to calculate the average BCS change for HD = −0.88 ± 0.24, HI = 1.13 ± 0.24, LD = −1.5 ± 0.29, LI = 0.88 ± 0.38, CD = −1.38 ± 0.13, and CI = 1.35 ± 0.14. Statistical comparison of final observed and model predicted values revealed acceptable precision when predicting BCS and BW respectively in control horses (r(2) = 0.91, 0.98) but less precision when predicting body fat (BF) (r(2) = 0.51). Model precision for BCS, BW, and BF respectively in lightly (r(2) = 0.29, 0.85, 0.57) and heavily (r(2) = 0.04, 0.84, 0.13) exercised horses was low. Model accuracy was acceptable across all treatments when predicting BW (C(b) = 0.97, 0.96, 0.98). However, accuracy varied when predicting BCS (C(b) = 0.82, 0.89, 0.41) and BF (C(b) = 0.80, 0.55, 0.87) for the control, light, and heavy exercise groups, respectively. These results indicate that the revised model is acceptable for sedentary horses but the predictability of the model was insensitive to the exercising horse, therefore the exercise energy expenditure formulas incorporated into the model require revision. Packaging this model in a format that facilitates industry application could lead to more efficient feeding practices of sedentary horses, generating health, and economic benefit. Further investigation into energy expenditure of exercising horses could yield a model with broader applications.

PROBLEM: Quantitative feedback from students about their clinical learning experiences is used to inform program quality, but the extent to which tools are reliable, valid and refined receives less attention. AIM: To evaluate the psychometric properties of the Midwifery Student Evaluation of Practice (MidSTEP) tool using Rasch analysis. METHODS: The Midwifery Student Evaluation of Practice tool was completed by Bachelor of Midwifery students (n = 901) attending seven universities in Australia and New Zealand. The tool consists of the Clinical Learning Environment Scale (16 items) and Impact of the Midwifery Preceptor Scale (10 items), each with two subscales. Rasch analysis was conducted on all subscales separately using the partial credit model of RUMM2030. Response format, item fit, dimensionality of the scale and its targeting were assessed. RESULTS: Rasch analysis confirmed the internal construct validity of the Clinical Learning Environment and Impact of the Midwifery Preceptor subscales, with no evidence of mis-fitting items, local dependency or multidimensionality. The 4-point response scale was found to be appropriate, and internal consistency reliability of each subscale was good. DISCUSSION: Results provide support for the reliability and validity of the Midwifery Student Evaluation of Practice tool. The four subscales can confidently be used in undergraduate midwifery clinical education. The use of Rasch analysis is consistent with growing awareness in health and education of the need to apply more advanced, sophisticated psychometric techniques to ensure measures are suitable for their intended use. TWEETABLE ABSTRACT: Midwifery students clinical learning experiences should be measured using robust tools. MidSTEP is reliable and valid.

ObjectivesTo evaluate parent and teacher opinion of the provision of in-school eyecare and jargon-free written reporting of visual status for children in special educational settings.Participants and methodsA nationally-agreed, in-school eyecare framework for children attending special schools which recommends a full eye examination, dispensing of spectacles and provision of a jargon-free written report of visual outcomes to parents and teachers, was provided to 200 children (mean age 10 years, 9 months; 70% male) attending a special school in the UK. The written 'Vision Report' detailed, in lay-language, results from the eye examination and provided practical advice to alleviate the impact of vision difficulties both at home and in the classroom. Following implementation of the framework, parents and teachers completed a feedback questionnaire to determine their opinion of the in-school eye examination and utility of the Vision Report.ResultsParents of 123 participants returned a feedback questionnaire. Eighty-eight participants were represented by the 23 teachers who returned a questionnaire. The in-school eyecare was rated positively for children in special education by 82.4% of parents and 80.9% of teachers. Key benefits included the familiarity of the in-school setting (81.3% of parents and 100% of teachers agree), the convenience of the setting for parents (74.0% of parents and 100% of teachers agree), and the opportunity for teachers to speak directly to eyecare providers regarding a child's visual needs (82.6% of teachers agree). The information provided by the Vision Report was deemed useful day-to-day by 78.3% of parents and 100% of teachers. The majority (80%) of teachers implemented classroom modifications suggested in the report, whereas only 47.9% of parents reported implementation of modifications at home.ConclusionsProvision of in-school eyecare is valued by parents and teachers of children in special education settings. Jargon-free, written reports of visual status are valued and utilised by parents and teachers. Further support is required to aid parents in implementing vision modifications at home.

Background Pharmacokinetic data show reduced mycophenolic acid levels in renal transplant recipients taking mycophenolate mofetil (MMF) and proton pump inhibitors (PPIs) concomitantly. This reduced exposure could increase rejection risk. The typical initial MMF dose post renal transplantation is 2 g/day, which often requires dose reduction secondary to side effects. Existing studies have not shown significant acute rejection differences for patients taking MMF-PPI versus patients taking MMF-ranitidine. Objective The purpose of this study was to evaluate clinical outcomes in renal transplant recipients receiving a lower MMF dose than previously studied (1.5 g/day) and either a PPI or histamine-2 receptor antagonist (H2RA). Methods This retrospective cohort study included adult subjects receiving a renal transplant between January 1, 2009, and June 30, 2013. Comparison groups were defined based on acid-suppressing therapy class prescribed at discharge from transplantation. The primary outcome was acute rejection incidence within 1 year posttransplantation. Results Of 728 renal transplant recipients screened, 522 were included: 183 taking a PPI and 339 taking an H2RA. There was no significant difference in acute rejection within 1 year (H2RA 19% versus PPI 14%, p=0.12) or 3 months (4% vs 5%, p=0.44, respectively) posttransplantation. Maintenance immunosuppression (MMF dose and tacrolimus troughs) was similar between groups at 3 months and 1 year. Graft and patient survivals were favorable (> 95%), and graft function at 1 year was stable and similar between groups. Conclusion Despite taking lower MMF doses than previously studied, subjects on a PPI compared to an H2RA were not at increased risk of acute rejection within 1 year posttransplantation.

Objective: The purpose of this study was to evaluate, by means of cephalometric appraisal, the vertical effects of non-extraction treatment of adult anterior open bite with clear aligners (Invisalign system, Align Technology, Santa Clara, CA, USA). Methods: Lateral cephalograms of 30 adult patients with anterior open bite treated using Invisalign (22 females, 8 males; mean age at start of treatment: 28 years and 10 months; mean anterior open bite at start of treatment: 1.8 mm) were analyzed. Pre- and post-treatment cephalograms were traced to compare the following vertical measurements: SN to maxillary occlusal plane (SN-MxOP), SN to mandibular occlusal plane (SN-MnOP), mandibular plane to mandibular occlusal plane (MP-MnOP), SN to mandibular plane (SN-MP), SN to palatal plane (SN-PP), SN to gonion-gnathion plane (SN-GoGn), upper 1 tip to palatal plane (U1-PP), lower 1 tip to mandibular plane (L1-MP), mesiobuccal cusp of upper 6 to palatal plane (U6-PP), mesiobuccal cusp of lower 6 to mandibular plane (L6-MP), lower anterior facial height (LAFH), and overbite (OB). Paired t-tests and descriptive statistics were utilized to analyze the data and assess any significant changes resulting from treatment. Results: Statistically significant differences were found in overall treatment changes for SN-MxOP, SN-MnOP, MP-MnOP, SN-MP, SN-GoGn, L1-MP, L6-MP, LAFH, and OB. Conclusions: The Invisalign system is a viable therapeutic modality for non-extraction treatment of adult anterior mild open bites. Bite closure was mainly achieved by a combination of counterclockwise rotation of the mandibular plane, lower molar intrusion and lower incisor extrusion. RESUMO Objetivo: o objetivo desse estudo foi realizar uma avaliação cefalométrica dos efeitos verticais do tratamento sem extração de mordidas abertas anteriores em adultos com o uso de alinhadores (sistema Invisalign, Align Technology, Santa Clara, CA, EUA). Métodos: foram analisados cefalogramas laterais de 30 pacientes adultos com mordida aberta anterior, tratados com o sistema Invisalign (22 do sexo feminino, 8 do sexo masculino, com idade média ao início do tratamento de 28 anos e 10 meses, e mordida aberta anterior média igual a 1,8mm). Os cefalogramas pré- e pós-tratamento foram traçados e as seguintes medidas verticais foram avaliadas: SN ao plano oclusal maxilar (SN-MxOP), SN ao plano oclusal mandibular (SN-MnOP), plano mandibular ao plano oclusal mandibular (MP-MnOP), SN ao plano mandibular (SN-MP), SN ao plano palatino (SN-PP), SN ao plano gônio-gnátio (SN-GoGn), incisivo central superior ao plano palatino (U1-PP), incisivo central inferior ao plano mandibular (L1-MP), cúspide mesiovestibular do molar superior ao plano palatino (U6-PP), cúspide mesiovestibular do molar inferior ao plano mandibular (L6-MP), altura facial anterior inferior (AFAI) e sobremordida (OB). Testes t pareados e estatística descritiva foram utilizados para analisar os dados e as alterações significativas resultantes do tratamento. Resultados: foram encontradas diferenças estatisticamente significativas durante o tratamento para SN-MxOP, SN-MnOP, MP-MnOP, SN-MP, SN-GoGn, L1-MP, L6-MP, AFAI e OB. Conclusões: o sistema Invisalign é uma modalidade terapêutica viável para o tratamento sem extração de mordidas abertas anteriores em pacientes adultos. O fechamento da mordida foi obtido principalmente por uma combinação de rotação do plano mandibular no sentido anti-horário, intrusão molar inferior e extrusão do incisivo inferior.

OBJECTIVE To characterize aminoaciduria and plasma amino acid concentrations in dogs with hepatocutaneous syndrome (HCS). ANIMALS 20 client-owned dogs of various breeds and ages. PROCEDURES HCS was definitively diagnosed on the basis of liver biopsy specimens (n = 12), gross and histologic appearance of skin lesions (4), and examination of skin and liver biopsy specimens (2) and presumptively diagnosed on the basis of cutaneous lesions with compatible clinicopathologic and hepatic ultrasonographic (honeycomb or Swiss cheese pattern) findings (2). Amino acid concentrations in heparinized plasma and urine (samples obtained within 8 hours of each other) were measured by use of ion exchange chromatography. Urine creatinine concentration was used to normalize urine amino acid concentrations. Plasma amino acid values were compared relative to mean reference values; urine-corrected amino acid values were compared relative to maximal reference values. RESULTS All dogs had generalized hypoaminoacidemia, with numerous amino acid concentrations < 50% of mean reference values. The most consistent and severe abnormalities involved glutamine, proline, cysteine, and hydroxyproline, and all dogs had marked lysinuria. Urine amino acids exceeding maximum reference values (value > 1.0) included lysine, 1-methylhistidine, and proline. CONCLUSIONS AND CLINICAL RELEVANCE Hypoaminoacidemia in dogs with HCS prominently involved amino acids associated with the urea cycle and synthesis of glutathione and collagen. Marked lysinuria and prolinuria implicated dysfunction of specific amino acid transporters and wasting of amino acids essential for collagen synthesis. These findings may provide a means for tailoring nutritional support and for facilitating HCS diagnosis.

This report describes development of spherical equivalent refraction (SER) and axial length (AL) in two population-based cohorts of white, European children. Predictive factors for myopic growth were explored. Participants were aged 6–7- (n = 390) and 12–13-years (n = 657) at baseline. SER and AL were assessed at baseline and 3, 6 and 9 years prospectively. Between 6 and 16 years: latent growth mixture modelling identified four SER classes (Persistent Emmetropes-PEMM, Persistent Moderate Hyperopes-PMHYP, Persistent High Hyperopes-PHHYP and Emerging Myopes-EMYO) as optimal to characterise refractive progression and two classes to characterise AL. Between 12 and 22-years: five SER classes (PHHYP, PMHYP, PEMM, Low Progressing Myopes-LPMYO and High Progressing Myopes-HPMYO) and four AL classes were identified. EMYO had significantly longer baseline AL (≥ 23.19 mm) (OR 2.5, CI 1.05–5.97) and at least one myopic parent (OR 6.28, CI 1.01–38.93). More myopic SER at 6–7 years (≤ + 0.19D) signalled risk for earlier myopia onset by 10-years in comparison to baseline SER of those who became myopic by 13 or 16 years (p ≤ 0.02). SER and AL progressed more slowly in myopes aged 12–22-years (− 0.16D, 0.15 mm) compared to 6–16-years (− 0.41D, 0.30 mm). These growth trajectories and risk criteria allow prediction of abnormal myopigenic growth and constitute an important resource for developing and testing anti-myopia interventions.

There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo -p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies.

The Personal Wellbeing Index (PWI) is used internationally to measure subjective well-being. While numerous studies have reported on the psychometric properties of the PWI using classic test theory, the current paper provides additional psychometric evaluation using the Rasch measurement model. The responses to the PWI items of 593 healthy adults living in Australia or Canada were analysed using Rasch analysis. Assessed were overall model fit was assessed, individual person fit and item fit, reliability, differential item functioning (DIF), unidimensionality, targeting, and response format. Results indicate excellent psychometric properties of the PWI, provided the religion/spirituality item is excluded. The seven-item PWI showed good model fit (overall item–trait interaction χ 2 = 70.59, df = 63, p = 0.24), excellent person separation (PSI = .89), no item or person misfit, and no DIF for country or gender, and unidimensionality was supported. In addition, only very mild disordered thresholds were observed for the ‘safety’ item, indicating that overall, the 11-point response format was suitable for this population. It is recommended that the religion/spirituality item not be included in the aggregated or averaged total score in Western context and that caution should be used in comparison across different groups where the eight-item version has been used.

Background The Practice Environment Scale (PES) has been used extensively to measure the quality of the practice environment of nurses working in a variety of work settings, and has been linked with quality of care, nurse wellbeing, job dissatisfaction and burnout. Although developed for nurses, many of the aspects addressed by the PES are also relevant to the midwifery profession, and may provide a tool to better understand midwives' decision to leave the profession. Aim To adapt the PES for use with midwives and to assess its psychometric properties. Methods An online survey containing the adapted version of the PES was distributed to a sample of hospital-employed New Zealand midwives ( n =600). Exploratory factor analysis was conducted to identify subscales which were compared for midwives who had, versus had not considered, leaving the midwifery profession. Findings Four subscales were identified, showing good internal consistency reliability ( Quality of Management , Midwife–Doctor Relations, Resource Adequacy and Opportunities for Development ). The lowest mean score was recorded for Resource Adequacy ( M =2.38). All subscales of the adapted 20-item PES:Midwives were significant predictors of the decision to leave the profession ( p Quality of Management (OR=2.6). Conclusion The PES:Midwives was successfully adapted for use with midwives and provides a psychometrically sound tool for research to identify factors associated with the wellbeing, job satisfaction and risk of attrition amongst hospital employed midwives. The PES:Midwives also provides a means of comparing the practice environment across different models of care and employing organizations.

The WDEQ-A is the most widely used measure of childbirth fear in pregnant women; however there is increasing discussion in the literature that simpler, more culturally transferrable tools may offer a better solution to identifying fearful women in clinical practice.To compare the two item Fear of Birth Scale (FOBS) with the 33 item WDEQ-A in a large cohort of Australian pregnant women.Self-report questionnaires during second trimester including Wijma Delivery Expectancy Questionnaire (WDEQ-A) and Fear of Birth Scale (FOBS). Correlation of FOBS and WDEQ-A was tested using Spearman's correlation coefficients. Receiver operating characteristic (ROC) curve assessed the sensitivity and specificity of possible cut-points on the FOBS against WDEQ-A cut-point of ≥85. Sensitivity, specificity, positive and negative predictive values were determined. Fearful and non-fearful women as classified by both instruments were compared for differences in demographic, psycho-social and obstetric characteristics.1410 women participated. The correlation between the instruments was strong (Spearman's Rho = 0.66, p 0.001). The area under the ROC was 0.89 indicating high sensitivity with a FOBS cut-point of 54. Sensitivity was 89%, specificity 79% and Youden index 0.68. Positive predictive value was 85% and negative predictive value 79%. Both instruments identified high fear as significantly associated with first time mothers, previous emergency caesarean and women with self-reported anxiety and/or depression. Additionally FOBS identified a significant association between fearful women and preference for caesarean.This study supports the use of the FOBS in clinical practice to identify childbirth fear in pregnant women.

Glucocorticoids are primary stress hormones, and their synthetic derivatives are widely used clinically. The therapeutic efficacy of these steroids is limited by side effects and glucocorticoid resistance. Multiple glucocorticoid receptor (GR) isoforms are produced from a single gene by alternative translation initiation; however, the role individual isoforms play in tissue-specific responses to glucocorticoids is unknown. We have generated knockin mice that exclusively express the most active receptor isoform, GR-C3. GR-C3 knockin mice die at birth due to respiratory distress. Microarray analysis of fibroblasts from wild-type and GR-C3 mice indicated that most genes regulated by GR-C3 were unique to this isoform. Antenatal glucocorticoid administration rescued GR-C3 knockin mice from neonatal death. Dual-energy X-ray absorptiometry revealed no major alterations in body composition for rescued knockin mice. Rescued female, but not male, GR-C3 mice exhibited increased wheel running activity in the light portion of the day. LPS administration induced premature mortality in rescued GR-C3 knockin mice, and gene expression studies revealed a deficiency in the ability of GR-C3 to repress a large cohort of immune and inflammatory response genes. These findings demonstrate that specific GR translational isoforms can influence development, circadian rhythm, and inflammation through the regulation of distinct gene networks.-Oakley, R. H., Ramamoorthy, S., Foley, J. F., Busada, J. T., Lu, N. Z., Cidlowski, J. A. Glucocorticoid receptor isoform-specific regulation of development, circadian rhythm, and inflammation in mice.

Finding methods to facilitate efficient assimilation of relevant health care information is important for quality outcomes, including promoting maximal wellness and optimal patient outcomes in vulnerable populations. The Internet is a promising information resource that can be used to reach those suffering from depression, but evidence of its efficacy in this population is lacking. This study was designed to examine The Stress Gym intervention, a web-enhanced behavioral self-management program (WEB-SM) consisting of nine modules focused on the management of stress and depression. The effect of the Stress Gym intervention on depressive symptoms, stress, and attention was examined, from pre- to post-intervention, in participants with stress and in participants who were experiencing both stress and depressive symptoms. A statistically significant decrease in depressive symptoms and stress was observed and there was a statistically significant increase in attention after the Stress Gym intervention, on average, for all participants. This study supports the efficacy of Stress Gym as a tool to reduce depressive symptoms, stress, and attentional difficulties. There were significant improvements in participants overall and for participants when they were segregated into two groups, those with stress only and those with depressive symptoms and stress. With many patients choosing to explore health concerns online, it is important to have evidence-based programs available online that can help them manage their symptoms.

PURPOSE. We explored risk factors for myopia in 12- to 13-year-old children in Northern Ireland (NI). METHODS. Stratified random sampling was performed to obtain representation of schools and children. Cycloplegia was achieved using cyclopentolate hydrochloride 1%. Distance autorefraction was measured using the Shin-Nippon SRW-5000 device. Height and weight were measured. Parents and children completed a questionnaire, including questions on parental history of myopia, sociodemographic factors, childhood levels of near vision, and physical activity to identify potential risk factors for myopia. Myopia was defined as spherical equivalent ≤0.50 diopters (D) in either eye. RESULTS. Data from 661 white children aged 12-to 13-years showed that regular physical activity was associated with a lower estimated prevalence of myopia compared to sedentary lifestyles (odds ratio [OR] = 0.46 adjusted for age, sex, deprivation score, family size, school type, urbanicity; 95% confidence interval [CI], 0.23–0.90; P for trend = 0.027). The odds of myopia were more than 2.5 times higher among children attending academically-selective schools (adjusted OR = 2.66; 95% CI, 1.48–4.78) compared to nonacademically-selective schools. There was no evidence of an effect of urban versus nonurban environment on the odds of myopia. Compared to children with no myopic parents, children with one or both parents being myopic were 2.91 times (95% CI, 1.54–5.52) and 7.79 times (95% CI, 2.93– 20.67) more likely to have myopia, respectively. CONCLUSIONS. In NI children, parental history of myopia and type of schooling are important determinants of myopia. The association between myopia and an environmental factor, such as physical activity levels, may provide insight into preventive strategies.

Evaluation of the central nervous system (CNS) in the developing mouse presents unique challenges, given the complexity of ontogenesis, marked structural reorganization over very short distances in 3 dimensions each hour, and numerous developmental events susceptible to genetic and environmental influences. Developmental defects affecting the brain and spinal cord arise frequently both in utero and perinatally as spontaneous events, following teratogen exposure, and as sequelae to induced mutations and thus are a common factor in embryonic and perinatal lethality in many mouse models. Knowledge of normal organ and cellular architecture and differentiation throughout the mouse’s life span is crucial to identify and characterize neurodevelopmental lesions. By providing a well-illustrated overview summarizing major events of normal in utero and perinatal mouse CNS development with examples of common developmental abnormalities, this annotated, color atlas can be used to identify normal structure and histology when phenotyping genetically engineered mice and will enhance efforts to describe and interpret brain and spinal cord malformations as causes of mouse embryonic and perinatal lethal phenotypes. The schematics and images in this atlas illustrate major developmental events during gestation from embryonic day (E)7.5 to E18.5 and after birth from postnatal day (P)1 to P21.

Normal mammary gland development may be altered by exposure to environmental toxicants and pharmaceutical products, excessive exposure to hormones, and genetic alterations. Mammary gland whole mounts are an inexpensive method to capture the progression of morphological changes that may arise after exposure. However, in later life, when abnormalities are more prone to develop, sole reliance on this one method may not always provide enough information to make a proper diagnosis of the abnormality. Historically, in chemical test guideline studies, a single mammary gland is removed at necropsy and prepared as a hematoxylin and eosin (H&E)-stained section. The incorporation of contralateral mammary whole-mount collection and analysis decreases the likelihood of a false-negative assessment. Evaluation of the whole mount is limited by the presence of one or two entire mammary glands on a slide, and in some cases, the abnormalities observed in the whole mount are not uniformly represented in the H&E section. The goal of this study was to develop a protocol for converting coverslipped mammary whole mounts to H&E-stained sections so that lesions that would otherwise have been missed or that are difficult to diagnose can be identified. Here, we detail a method to produce a high-quality, paraffin-embedded H&E section from a mammary gland that was initially prepared as a whole mount. In comparison to a tissue that was intentionally prepared for H&E sectioning, the whole mount requires additional preparation for tissue removal and processing. However, this method is considered inexpensive, as it requires common lab reagents and little additional time. As a result, this method can provide invaluable information on how chemical and environmental exposures alter normal mammary development, as well as display changes that occur because of genetic modifications.

Background The health and wellbeing of midwives are important considerations for workforce retention and quality care. The occurrence and relationships among mental health conditions such as burnout and depression have received little attention. We investigated the prevalence of burnout, depression, anxiety and stress in Australian midwives. Methods An online survey was conducted in September 2014. Participants were recruited through the Australian College of Midwives and professional networks. The survey sought personal and professional details. Standard measures included the Copenhagen Burnout Inventory (CBI) (Personal, Work and Client subscales), and Depression, Anxiety, and Stress Scale (DASS). The sample was collapsed into two groups according to DASS clinical cut-offs (normal/mild versus moderate/severe/extreme). Effect size statistics were calculated and judged according to Cohen’s guidelines. Results One thousand thirty-seven surveys were received. Respondents were predominantly female (98%), with an average age of 46.43 years, and 16.51 years of practice. Using a CBI subscale cut-off score of 50 and above (moderate and higher), 64.9% (n = 643) reported personal burnout; 43.8% (n = 428) reported work-related burnout; and 10.4% (n = 102) reported client-related burnout. All burnout subscales were significantly correlated with depression, anxiety and stress, particularly personal and work-related burnout with Spearman’s rho correlations ranging from .51 to .63 (p

Purpose: The EORTC Quality of Life Questionnaire is a widely used cancer-specific quality of life instrument comprising a core set of 30 items (QLQ-C30) supplemented by cancer site-specific modules. The purpose of this paper was to examine the extent to which the conventional multi-item domain structure of the QLQ-C30 holds across patients with seven different primary cancer sites.Methods: Multi-group confirmatory factor analysis was used to test whether a measurement model of the QLQ-C30 was invariant across cancer sites. Configural (same patterns of factor loadings), metric (equivalence of factor loadings) and scalar (equivalence of thresholds) invariance amongst the cancer site groups were assessed (N = 1,906) by comparing the fit of a model with these parameters freely estimated to a model where estimates were constrained to be equal for the corresponding items in each group.Results: All groups exhibited good model fit except for the prostate group, which was excluded. Only 1 of 576 parameters was found to differ between primary sites: specifically, the first threshold of Item 1 in the breast cancer group exhibited non-invariance. In a post hoc analysis, several instances of non-invariance by treatment status (baseline, on-treatment, off-treatment) were observed.Conclusions: Given only one instance of non-invariance between cancer sites, there is a reason to be confident in the validity of conclusions drawn when comparing QLQ-C30 domain scores between different sites and when interpreting the scores of heterogeneous samples, although future research should assess the potential impact of confounding variables such as treatment and gender.

The distress thermometer (DT) is commonly used in cancer care to improve detection of distress. The DT's recommended cut-off score of 4 or 5 has typically been established using the Hospital Anxiety and Depression Scale (HADS) by receiver operating characteristic curve analysis. The present analysis complements these studies by critically examining the use of the HADS to identify the DT's cut-off score and corroborating the DT's cut-off scores using item response theory (Rasch analysis).The DT and HADS were completed by 340 patients with cancer. Rasch dimensionality analysis was performed on the HADS-Total, and test characteristic curves were examined to equate the DT and the HADS subscales. Identified DT cut-off scores were then examined for their sensitivity and specificity.Rasch analysis did not support the unidimensionality of HADS-Total. The test characteristic curves indicated that a cut-off score of ≥8 on the HADS-Anxiety and HADS-Depression subscales was equivalent to a score of 6 and 7 on the DT, respectively. However, a DT cut-off score of 5 resulted in the best balance between sensitivity and specificity across the HADS-Anxiety and HADS-Depression subscales.Despite being a popular practice, the present findings did not support combining the HADS-Anxiety and HADS-Depression subscales to identify the DT's cut-off score. Furthermore, these results inform the use of the DT as a preliminary screening tool and suggest that when a single screen is used, a DT cut-off score of 6 or 7 might be more appropriate than the typical cut-off score of 4.

Overview: Working music theater singers (MTS) typically have a heavy vocal load and little is known about their perception of vocal function. The Evaluation of the Ability to Sing Easily (EASE) was used to assess professional MTS' perceptions of current singing voice status and to compare scores across demographic and performance characteristics and to evaluate the construct validity of the EASE and its subscales (VF = Vocal Fatigue, PRI = Pathologic-Risk Indicators). Methods: Professional MTS (n = 284) completed an online survey including the EASE and two additional Vocal Concern (VC) items. Scores were compared across age, gender, whether currently working, role, perceived vocal load over the past 24 h and self-reported voice problem. Results: For the whole cohort, statistically significant differences were found on all subscales according to whether or not singers perceived themselves to have a voice problem (p < 0.001). Currently performing singers were significantly different from those not performing in a show on the EASE Total (p = 0.014) and VF (p = 0.002), but not for PRI and VC. In the currently performing singer group, significant differences were found for gender, role and perceived voice problem on the EASE Total and all subscales (p < 0.01). Significantly higher VF scores were recorded for singers with heavy vocal load (p = 0.01), but there were no differences on the EASE Total (p = 0.57), PRI (p = 0.19) or VC subscales (p = 0.53). Among these performing singers, no significant age differences were found for any EASE subscales. Conclusions: These findings provide further validation of the EASE as a useful tool for measuring singers' perceptions of vocal function and suggest that the subscales should be scored separately. Future evaluation of the EASE against objective clinical assessments (e.g., videostroboscopy) is recommended. © 2014 S. Karger AG, Basel

ObjectivesTo determine whether implementation of comprehensive in-school eyecare results in measurable benefits for children and young people in terms of visual status, classroom behaviours and how well their visual needs are met.DesignSchool-based observational study.Participants & methods200 pupils [mean age 10 years 9 months, 70% male, majority moderate (40%) or severe (35%) learning difficulty] of a special education school in the UK. A sector-agreed in-school eyecare framework including full eye examination and cycloplegic refraction, dispensing of spectacles (as appropriate) and written reporting of outcomes to parents/teachers was applied. Classroom behaviours were observed and recorded prior to, and after, the in-school eyecare. Surveys were employed to obtain visual histories from parents/teachers. School records and statutory documents were reviewed for diagnostic and learning disability classifications. Visual function and ocular health were profiled at baseline and significant visual deficits identified. Where such deficits were previously unrecognised, untreated or not compensated for (e.g. correction of refractive error, enlargement of educational material) they were recorded as 'unmet visual need'. At follow-up, 2-5 months after initial (baseline) measures, eye examinations, parent/teacher surveys and behaviour observations were repeated. Follow-up measures were used to determine if measurable improvements were evident in visual function, ocular health, the level of unmet need and classroom behaviour following implementation of in-school eyecare.Results199 participants completed baseline and follow-up measures. 122 (61%) participants presented with at least one significant visual or ocular health deficit and 90 (45%) participants had at least one unmet visual need. Younger pupils and those with no previous history of eyecare were more likely to demonstrate unmet visual needs at baseline (OR 1.12 95% CI 1.03 to 1.21) p = 0.012; (OR 4.44 95% CI 1.38 to 14.29 p = 0.007 respectively). On follow-up, the number of pupils with unmet visual needs dropped significantly to 36 (18%) (McNemar's test p0.05). Where significant refractive deficits were corrected at follow-up, near visual acuity improved significantly (Wilcoxon signed rank p = 0.013), however, poor spectacle compliance was a persistent cause of unmet visual need. Off-task behaviour reduced significantly after actions to address unmet visual needs were communicated to parents and teachers (Wilcoxon signed rank p = 0.035).ConclusionsThe present study demonstrates for the first time measurable visual and behaviour benefits to children in special education settings when they receive comprehensive in-school eye examinations, on-site spectacle dispensing and jargon-free reporting of outcomes to teachers and parents.

Summary Objectives Most voice self-rating tools are disease-specific measures and are not suitable for use with healthy voice users. There is a need for a tool that is sensitive to the subtleties of a singer's voice and to perceived physical changes in the singing voice mechanism as a function of load. The aim of this study was to devise and validate a scale to assess singer's perceptions of the current status of their singing voice. Methods Ninety-five vocal health descriptors were collected from focus group interviews of singers. These were reviewed by 25 currently performing music theater (MT) singers. Based on a consensus technique, the number of descriptors was decreased to 42 items. These were administered to a sample of 284 professional MT singers using an online survey to evaluate their perception of current singing voice status. Results Principal component analysis identified two subsets of items. Rasch analysis was used to evaluate and refine these sets of items to form two 10-item subscales. Both subscales demonstrated good overall fit to the Rasch model, no differential item functioning by sex or age, and good internal consistency reliability. The two subscales were strongly correlated and subsequent Rasch analysis supported their combination to form a single 20-item scale with good psychometric properties. Conclusions The Evaluation of the Ability to Sing Easily (EASE) is a concise clinical tool to assess singer's perceptions of the current status of their singing voice with good measurement properties. EASE may prove a useful tool to measure changes in the singing voice as indicators of the effect of vocal load. Furthermore, it may offer a valuable means for the prediction or screening of singers “at risk” of developing voice disorders.

Background: Satisfaction with antenatal care could differ depending on the organisation and the context of care. Aim: To compare antenatal care in Australia and Sweden, to identify deficiencies in the content of antenatal care and what aspects contributed most in dissatisfaction with antenatal care. Methods: A longitudinal survey of 123 Australian and 386 Swedish women recruited during one year in regional hospitals in Sweden and Australia. Data collected by three questionnaires. Results: Women in Australia had more antenatal visits, less continuity of midwife caregiver but were more satisfied with antenatal education and the emotional aspects of antenatal care. Although the overall satisfaction was high, deficiencies were found in more than half of the studied variables in the content of care. Women in Sweden were more dissatisfied with information about labour and birth (OR 3.1; 1.8-5.3) and information about the time following birth (OR 3.8; 2.2-6.3), but more satisfied with the involvement of the father (OR 0.3; 0.2-0.6). Factors that contributed most to dissatisfaction with antenatal care overall were deficiency in information about pregnancy related issues (OR 3.4; 1.3-8.7) and not being taken seriously by the midwife (OR 4.1; 1.6-10.1). Conclusion: Satisfaction with antenatal care was high in both groups of women. Australian women were more satisfied than the Swedish women with the emotional aspects of care. Deficiencies were found in more than half of the variables measured relating to the specific aspects of care. Lack of information and not being treated seriously were important factors for not being satisfied.

The early infant-mother attachment relationship is part of a network of close relationships in which the relationship between parents is especially relevant. Evidence for linkages between maternal satisfaction with the partner relationship and infant-mother attachment is equivocal. The current study tested whether associations between partner relationship dissatisfaction and infant-mother attachment quality might be conditional on mothers' parenting self-efficacy. The bivariate effect of partner relationship dissatisfaction on infant-mother attachment as well as moderation of this effect by parenting self-efficacy was tested in a sample of 260 infant-mother dyads 1 year after birth. There was no direct effect of partner dissatisfaction on attachment. Unexpectedly, for high parenting self-efficacy, greater partner dissatisfaction increased the odds of an avoidant infant attachment (compared with a disorganized) whereas, for low parenting self-efficacy, greater partner dissatisfaction decreased the odds of an avoidant infant attachment (compared with secure and disorganized). Findings underline the importance of parenting cognitions for understanding contextual factors of infant-mother attachment quality. (PsycINFO Database Record

Allosteric potentiators amplify the sensitivity of physiologic control circuits, a mode of action that could provide therapeutic advantages. This hypothesis was tested with the dopamine D1 receptor potentiator DETQ [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one]. In human embryonic kidney 293 (HEK293) cells expressing the human D1 receptor, DETQ induced a 21-fold leftward shift in the cAMP response to dopamine, with a Kb of 26 nM. The maximum response to DETQ alone was ∼12% of the maximum response to dopamine, suggesting weak allosteric agonist activity. DETQ was ∼30-fold less potent at rat and mouse D1 receptors and was inactive at the human D5 receptor. To enable studies in rodents, an hD1 knock-in mouse was generated. DETQ (3-20 mg/kg orally) caused a robust (∼10-fold) increase in locomotor activity (LMA) in habituated hD1 mice but was inactive in wild-type mice. The LMA response to DETQ was blocked by the D1 antagonist SCH39166 and was dependent on endogenous dopamine. LMA reached a plateau at higher doses (30-240 mg/kg) even though free brain levels of DETQ continued to increase over the entire dose range. In contrast, the D1 agonists SKF 82958, A-77636, and dihydrexidine showed bell-shaped dose-response curves with a profound reduction in LMA at higher doses; video-tracking confirmed that the reduction in LMA caused by SKF 82958 was due to competing stereotyped behaviors. When dosed daily for 4 days, DETQ continued to elicit an increase in LMA, whereas the D1 agonist A-77636 showed complete tachyphylaxis by day 2. These results confirm that allosteric potentiators may have advantages compared with direct-acting agonists.

Background Fear of childbirth has negative consequences for a woman's physical and emotional wellbeing. The most commonly used measurement tool for childbirth fear is the Wijma Delivery Expectancy Questionnaire (WDEQ-A). Although originally conceptualized as unidimensional, subsequent investigations have suggested it is multidimensional. This study aimed to undertake a detailed psychometric assessment of the WDEQ-A; exploring the dimensionality and identifying possible subscales that may have clinical and research utility. Methods WDEQ-A was administered to a sample of 1410 Australian women in mid-pregnancy. The dimensionality of WDEQ-A was explored using exploratory (EFA) and confirmatory factor analysis (CFA), and Rasch analysis. Results EFA identified a four factor solution. CFA failed to support the unidimensional structure of the original WDEQ-A, but confirmed the four factor solution identified by EFA. Rasch analysis was used to refine the four subscales (Negative emotions: five items; Lack of positive emotions: five items; Social isolation: four items; Moment of birth: three items). Each WDEQ-A Revised subscale showed good fit to the Rasch model and adequate internal consistency reliability. The correlation between Negative emotions and Lack of positive emotions was strong, however Moment of birth and Social isolation showed much lower intercorrelations, suggesting they should not be added to create a total score. Conclusion This study supports the findings of other investigations that suggest the WDEQ-A is multidimensional and should not be used in its original form. The WDEQ-A Revised may provide researchers with a more refined, psychometrically sound tool to explore the differential impact of aspects of childbirth fear. Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-1157-8) contains supplementary material, which is available to authorized users.

Objective To evaluate the internal construct validity and dimensionality of a new patient-reported outcome measure for people with traumatic brachial plexus injury (BPI) based on the International Classification of Functioning, Disability and Health definition of activity. Design Cross-sectional study. Setting Outpatient clinics. Participants Adults (age range, 18–82y) with a traumatic BPI (N=106). Interventions There were 106 people with BPI who completed a 51-item 5-response questionnaire. Responses were analyzed in 4 phases (missing responses, item correlations, exploratory factor analysis, and Rasch analysis) to evaluate the properties of fit to the Rasch model, threshold response, local dependency, dimensionality, differential item functioning, and targeting. Main Outcome Measures Not applicable, as this study addresses the development of an outcome measure. Results Six items were deleted for missing responses, and 10 were deleted for high interitem correlations >.81. The remaining 35 items, while demonstrating fit to the Rasch model, showed evidence of local dependency and multidimensionality. Items were divided into 3 subscales: dressing and grooming (8 items), arm and hand (17 items), and no hand (6 items). All 3 subscales demonstrated fit to the model with no local dependency, minimal disordered thresholds, no unidimensionality or differential item functioning for age, time postinjury, or self-selected dominance. Subscales were combined into 3 subtests and demonstrated fit to the model, no misfit, and unidimensionality, allowing calculation of a summary score. Conclusions This preliminary analysis supports the internal construct validity of the Brachial Assessment Tool, a unidimensional targeted 4-response patient-reported outcome measure designed to solely assess activity after traumatic BPI regardless of level of injury, age at recruitment, premorbid limb dominance, and time postinjury. Further examination is required to determine test-retest reliability and responsiveness.

the predicted midwifery workforce shortages in several countries have serious implications for the care of women during pregnancy, birth and post partum. There are a number of factors known to contribute to midwifery shortages and work attrition. However, midwives assessment of their own professional identity and role (sense of empowerment) are perhaps among the most important. There are few international workforce comparisons.to compare midwives' sense of empowerment across Australia, New Zealand and Sweden using the Perceptions of Empowerment in Midwifery Scale-R (PEMS-Revised).a self-administered survey package was distributed to midwives through professional colleges and networks in each country. The surveys asked about personal, professional and employment details and included the Perceptions of Empowerment in Midwifery Scale-R (PEMS-Revised). Descriptive statistics for the sample and PEMS were generated separately for the three countries. A series of analysis of variance with posthoc tests (Tukey's HSD) were conducted to compare scale scores across countries. Effect size statistics (partial eta squared) were also calculated.completed surveys were received from 2585 midwives (Australia 1037; New Zealand 1073 and Sweden 475). Respondents were predominantly female (98%), aged 50-59 years and had significant work experience as a midwife (+20 years). Statistically significant differences were recorded comparing scores on all four PEMS subscales across countries. Moderate effects were found on Professional Recognition, Skills and Resources and Autonomy/Empowerment comparisons. All pairwise comparisons between countries reached statistical significance (p.001) except between Australia and New Zealand on the Manager Support subscale. Sweden recorded the highest score on three subscales except Skills and Resources which was the lowest score of the three countries. New Zealand midwives scored significantly better than both their Swedish and Australian counterparts in terms of these essential criteria.midwives in New Zealand and Sweden had a strong professional identity or sense of empowerment compared to their Australian counterparts. This is likely the result of working in more autonomous ways within a health system that is primary health care focused and a culture that constructs childbirth as a normal but significant life event. If midwifery is to reach its full potential globally then developing midwives sense of autonomy and subsequently their empowerment must be seen as a critical element to recruitment and retention that requires attention and strengthening.

Resistance to emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone used as preexposure prophylaxis (PrEP) has been detected in individuals who initiated PrEP during unrecognized acute HIV infection and, rarely, in PrEP breakthrough infections. PrEP-selected resistance could alter future treatment options, and therefore we sought to determine how long resistance persisted after PrEP cessation.The Partners PrEP Study was a randomized placebo-controlled trial of FTC/TDF or TDF as PrEP for HIV prevention. We previously reported that PrEP-related mutations (K65R, K70E or M184IV) were detected by 454 sequencing following seroconversion in nine individuals who acquired HIV during the Partners PrEP Study. In the current study, we used 454 sequencing to detect and quantify PrEP-related mutations in HIV RNA-positive plasma samples prior to seroconversion, as well as in plasma from 6, 12, and 24 months after PrEP cessation from these nine individuals.HIV RNA-positive, antibody-negative samples were available prior to seroconversion for four of nine individuals with resistance detected at seroconversion. In all four cases, K65R, K70E and M184IV were not detected prior to seroconversion, suggesting PrEP-related resistance was selected and not transmitted. All PrEP-selected mutations were no longer detectable by 6 months after PrEP cessation and remained undetectable at 12 and 24 months in the absence of antiretroviral therapy.Using highly sensitive assays, PrEP-selected resistance in plasma decays below detection by 6 months following drug cessation and remains undetectable for at least 24 months. Even high levels of resistance mutations during acute infection decay rapidly in the absence of ongoing PrEP exposure.

Identifying environmental exposures that cause adverse mammary gland outcomes in rodents is a first step in disease prevention in humans and domestic pets. “Whole mounts” are an easy and inexpensive tissue preparation method that can elucidate typical or abnormal mammary gland morphology in rodent studies. Here, we propose procedures to facilitate the use of whole mounts for histological identification of grossly noted tissue alterations. We noted lesions in mammary whole mounts from 14-month-old CD-1 mice that were not found in the contralateral gland hematoxylin and eosin (H&E)-stained section. Whole mounts were removed from the slide and carefully processed to produce high-quality histological sections that mirrored the quality of the original H&E-stained section in order to properly diagnose the unidentified gross abnormalities. Incorporation of this method into testing protocols that focus on human relevant chemical and endocrine disruptors exposure will increase the chances of identifying lesions in the gland and reduce the risk of false negative findings. This method can be especially invaluable when lesions are not always palpable during the course of the study or visible at necropsy, or when a single cross section of the mammary gland is otherwise used for detecting lesions.

PURPOSE Stigma and lack of access to providers create barriers to mental health treatment for older adults living in the community. In order to address these barriers, we developed and evaluated a peer support intervention for older adults receiving Medicaid services. DESIGN AND METHODS Reclaiming Joy is a mental health intervention that pairs an older adult volunteer with a participant (older adult who receives peer support). Volunteers receive training on the strengths-based approach, mental health and aging, goal setting and attainment, community resources, and safety. Participant-volunteer pairs meet once a week for 10 weeks. Participants establish and work toward goals (e.g., better self-care, social engagement) that they feel would improve their mental health and well-being. Aging services agencies provide a part time person to manage the program, match volunteers and participants, and provide ongoing support. Outcomes evaluation for this pilot study included pre/postintervention assessments of participants. RESULTS Thirty-two participants completed the intervention. Pre/postassessment group means showed statistically significant improvement for depression but not for symptoms of anxiety. Quality-of-life indicators for health and functioning also improved for participants with symptoms of both depression and anxiety. IMPLICATIONS The Reclaiming Joy peer support intervention has potential for reducing depression and increasing quality of life in low-income older adults who have physical health conditions. It is feasible to administer and sustain the intervention through collaborative efforts with minimal program resources and a small amount of technical assistance.

Charcot-Marie-Tooth disease (CMT) is a common heritable peripheral neuropathy. There is no treatment for any form of CMT, although clinical trials are increasingly occurring. Patients usually develop symptoms during the first 2 decades of life, but there are no established outcome measures of disease severity or response to treatment. We identified a set of items that represent a range of impairment levels and conducted a series of validation studies to build a patient-centered multi-item rating scale of disability for children with CMT.As part of the Inherited Neuropathies Consortium, patients aged 3 to 20 years with a variety of CMT types were recruited from the USA, United Kingdom, Italy, and Australia. Initial development stages involved definition of the construct, item pool generation, peer review, and pilot testing. Based on data from 172 patients, a series of validation studies were conducted, including item and factor analysis, reliability testing, Rasch modeling, and sensitivity analysis.Seven areas for measurement were identified (strength, dexterity, sensation, gait, balance, power, endurance), and a psychometrically robust 11-item scale was constructed (CMT Pediatric Scale [CMTPedS]). Rasch analysis supported the viability of the CMTPedS as a unidimensional measure of disability in children with CMT. It showed good overall model fit, no evidence of misfitting items, and no person misfit, and it was well targeted for children with CMT.The CMTPedS is a well-tolerated outcome measure that can be completed in 25 minutes. It is a reliable, valid, and sensitive global measure of disability for children with CMT from the age of 3 years.

Objective: To examine the relevance and completeness of the International Classification of Functioning, Disability and Health (ICF) comprehensive core set for breast cancer using patient reported disability in an Australian cohort. Method: Cross-sectional community survey of 85 women following definitive treatment for primary breast cancer. Everyday living problems reported by participants (using open ended questionnaires) were linked with ICF categories using ‘linkage’ rules. Participants rated ‘Activities and Participation’ and ‘Environmental factors’ components of ICF checklist using World Health Organisation qualifiers (0–4). The impact of breast cancer on health areas corresponding to 90 ICF categories in these two components was assessed; and compared with ICF categories within the comprehensive breast cancer core set. Results: Participants identified 16 of 22 categories from ‘Activities and Participation’ and 11 of 23 categories (barriers) from ‘Environmental factors’ included in the comprehensive Core Set for BC, as relevant (≥ 10% of the participants). Median number of problems reported was 4 (IQR 1–9) and 1 (IQR 1–4) for ‘Activities and Participation’ and ‘Environmental factors’ categories’, respectively. Thirteen additional relevant categories relating to mobility, major life areas, community civic life and societal attitudes currently not included in the breast cancer core set, were identified. Conclusion: The comprehensive breast cancer core set needs to incorporate issues important to survivors with breast cancer in post-acute settings, prior to its validation from a global perspective.

Objective: The High-level Mobility Assessment Tool (HiMAT) was developed to measure high-level mobility limitations following traumatic brain injury. The aim of this study was to investigate if the revised HiMAT is valid for use with adults with neurological conditions other than traumatic brain injury. Design: Cross-sectional study. Subjects: Ninety-five participants with neurological conditions. Methods: HiMAT score sheets were retrieved from the central medical files of people who had attended a major rehabilitation facility for a neurological condition from January 2006 to October 2007. Additional HiMAT score sheets were submitted by therapists who participated in the HiMAT User’s Group. Rasch analysis (RUMM2030 software) was used to determine the overall fit of the model, individual item fit and differential item functioning. Results: Rasch analysis supported the internal validity of the revised eight-item HiMAT for individuals with neurological conditions. It showed good overall fit ( P = 0.74), no misfitting items and excellent internal consistency (Person Separation Index = 0.91). The HiMAT is unidimensional with no evidence of response dependency and no differential item functioning for age or sex. Conclusion: Further development of the revised HiMAT is required to investigate other aspects of validity, reliability and responsiveness in different neurological populations. However, the results support the internal validity of the revised HiMAT when used for people with neurological conditions who are able to walk without gait aids.

The normal embryonic development of organs and other tissues in mice and all species is preprogrammed by genes. Inactivation of a gene involved in any stage of normal embryonic development can have severe consequences leading to embryonic or postnatal developmental defects and lethality. Pathology methods are reviewed for evaluating normal and abnormal placenta and embryo, especially after E12.5. These methods include pathology protocols for necropsy and histopathology in addition to references that will provide additional knowledge for embryo assessment including histology atlases and advanced embryo imaging techniques.

As natural forest cover declines, planted forests have come to occupy an increasing percentage of the earth's surface, yet we know little about their suitability as alternative habitat for wildlife. Although some primate species use planted forests, few studies have compared primate populations in natural and nearby planted forests. From March 2006 to July 2010, we conducted line transect surveys and assessed group sizes and compositions in natural and nearby 60–70 year old mixed indigenous planted forest to determine the densities of diurnal primate species (Colobus guereza, Cercopithecus mitis, C. ascanius) in these two forest types at Isecheno, Kakamega Forest, Kenya. Line transect data were analyzed using the Encounter Rate, Whitesides, and Distance sampling methods, which all provided broadly consistent results. We found that all three diurnal primate species occupy both natural and planted forest at Isecheno. However, group densities of the two Cercopithecus species were 42–46% lower in planted than in natural forest. Colobus guereza achieved comparable group densities in the two forest types, although the species is found in smaller groups, and thus at lower (35%) individual density, in planted than in natural forest. Following a logging episode in the planted forest mid-way through our study, Cercopithecus ascanius group densities fell by 60% while C. mitis and Colobus guereza group densities remained stable over the next two years. Overall, our results suggest that while primate species vary in their response to habitat disturbance, planted forest has the potential to contribute to the conservation of some African monkey species. Even for the relatively flexible taxa in our study, however, 60–70 year old mixed indigenous planted forest failed to support densities comparable to those in nearby natural forest. From the perspective of Kakamega's primates, planted forests may supplement natural forest, but are not an adequate replacement for it. Am. J. Primatol. 73:1–14, 2011. © 2011 Wiley Periodicals, Inc.

The aim of this study was to replicate, in patients with multiple sclerosis (MS), the three-cluster cognitive-behavioral classification proposed by Turk and Rudy. Sixty-two patients attending a tertiary MS rehabilitation center completed the Pain Impact Rating questionnaire measuring activity interference, pain intensity, social support, and emotional distress. The General Health Questionnaire-28 and the Multiple Sclerosis Impact Scale-29 assessed disability and restriction in participation. Cluster analysis classified patients into three cognitive-behavioral groups (40.4%, 'adaptive copers'; 36.5%, 'dysfunctional'; and 23.1%, 'interpersonally distressed'). Patients in groups with higher levels of activity interference, emotional distress due to pain, and lower perceived levels of social support had significantly higher levels of depression on the General Health Questionnaire-28 (P0.003), and reported a greater impact on their physical and psychological functioning (P0.001) on Multiple Sclerosis Impact Scale-29 subscales. Possible cut-points were identified to aid clinicians in classifying patients into clusters for individualized treatment. More research is needed to improve the understanding of pain and the potential use of cognitive-behavioral clusters in patients with MS. These may be useful in the development of tailored early intervention, which may reduce pain-related disability and contribute to patient's overall well being.

OBJECTIVE: To assess the effectiveness of a high- vs low--intensity multidisciplinary ambulatory rehabilitation programme over 12 months for persons in the chronic phase after Guillain-Barre syndrome (pwGBS) in an Australian community cohort. METHOD: A total of 79 pwGBS, recruited from a tertiary hospital, were randomized to a treatment group (n = 40) for an individualized high-intensity programme, or a control group (n = 39) for a lower intensity programme. The primary outcome the Functional Independence Measure (FIM) motor subscale assessed "activity limitation"; while secondary measures for "participation" included: World Health Organization Quality of Life; Depression, Anxiety Stress Scale; and Perceived Impact Problem Profile (PIPP) scales. All outcome measures were assessed at baseline and at 12 months. RESULTS: Intention to treat analysis of data from 69 participants (treatment n = 35, control n = 34) showed reduced disability in the treatment group in post-treatment FIM domains (mobility, transfers, sphincter control and locomotion; all p

To assess the link between multimorbidity, type of chronic physical health problems and depressive symptoms The study was a cross-sectional postal survey conducted in 30 General Practices in Victoria, Australia as part of the diamond longitudinal study. Participants included 7,620 primary care attendees; 66% were females; age range from 18 to 76 years (mean = 51years SD = 14); 81% were born in Australia; 64% were married and 67% lived in an urban area. The main outcome measures include the Centre for Epidemiologic Studies Depression Scale (CES-D) and a study-specific self-report check list of 12 common chronic physical health problems. The prevalence of probable depression increased with increasing number of chronic physical conditions (1 condition: 23%; 2 conditions: 27%; 3 conditions: 30%; 4 conditions: 31%; 5 or more conditions: 41%). Only 16% of those with no listed physical conditions recorded CES-D scores of 16 or above. Across the listed physical conditions the prevalence of ‘probable depression’ ranged from 24% for hypertension; 35% for emphysema; 35% for dermatitis to 36% for stroke. The dose–response relationship is reduced when functional limitations and self-rated health are taken into account, suggesting that these factors mediate the relationship. A clear dose–response relationship exists between the number of chronic physical problems and depressive symptoms. The relationship between multimorbidity and depression appears to be mediated via self-perceived health related quality of life. Primary care practitioners will identify more cases of depression if they focus on those with more than one chronic health problem, no matter what the problems may be, being especially aware in the group who rate their health as poor/fair.

Cytochrome P-450 (CYP)-derived epoxyeicosatrienoic acids (EETs) possess potent anti-inflammatory effects in vitro. However, the effect of increased CYP-mediated EET biosynthesis and decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on vascular inflammation in vivo has not been rigorously investigated. Consequently, we characterized acute vascular inflammatory responses to endotoxin in transgenic mice with endothelial expression of the human CYP2J2 and CYP2C8 epoxygenases and mice with targeted disruption of Ephx2. Compared to wild-type controls, CYP2J2 transgenic, CYP2C8 transgenic, and Ephx2−/− mice each exhibited a significant attenuation of endotoxin-induced activation of nuclear factor (NF)-κB signaling, cellular adhesion molecule, chemokine and cytokine expression, and neutrophil infiltration in lung in vivo. Furthermore, attenuation of endotoxin-induced NF-κB activation and cellular adhesion molecule and chemokine expression was observed in primary pulmonary endothelial cells isolated from CYP2J2 and CYP2C8 transgenic mice. This attenuation was inhibited by a putative EET receptor antagonist and CYP epoxygenase inhibitor, directly implicating CYP epoxygenase-derived EETs with the observed anti-inflammatory phenotype. Collectively, these data demonstrate that potentiation of the CYP epoxygenase pathway by either increased endothelial EET biosynthesis or globally decreased EET hydrolysis attenuates NF-κB-dependent vascular inflammatory responses in vivo and may serve as a viable anti-inflammatory therapeutic strategy.—Deng, Y., Edin, M. L., Theken, K. N., Schuck, R. N., Flake, G. P., Kannon, M. A., DeGraff, L. M., Lih, F. B., Foley, J., Bradbury, J. A., Graves, J. P., Tomer, K. B., Falck, J. R., Zeldin, D. C., Lee, C. R. Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice.

A stratified, randomised, waitlist controlled study over 12 months assessed the effectiveness of a 6 week bladder rehabilitation programme in persons with multiple sclerosis (pwMS) in an Australian community cohort.Patients with definite MS and bladder issues (n=74) recruited from a tertiary hospital database were randomised to a treatment group (n=40) for an individualised bladder rehabilitation programme or to a control waitlist group (n=34). The Urogenital Distress Inventory (UDI6), Neurological Disability Scale (NDS) and the American Urological Association Symptom Index (AUA) assessed bladder impairment and 'activity limitation'; a single Quality of life (QoL) item in the AUA and the Incontinence Impact Questionnaire (IIQ7) measured restriction in 'participation'. Primary outcome measures were assessed at baseline and at 12 months.Analysis of per protocol data from 58 patients (treatment n=24, control n=34) showed reduced disability in the treatment group, with significant differences (p0.001) and large effect sizes (0.5) in post-treatment UDI6, NDS, AUA total, AUA QoL and IIQ7 scores for the two groups. The treatment group compared with the control group showed improvement: 78% versus 27% for UDI6 and 59% versus 17% improved for IIQ7. More patients in the control group deteriorated over the study period on the UDI6 (30% vs 0%; p0.001) and IIQ7 (39 vs 0%; p=0.001).A multifaceted, individualised bladder rehabilitation programme reduces disability and improves QoL in pwMS compared with no intervention after 12 months of follow-up. Information on specific interventions in different bladder types in MS and the impact on QoL need further evaluation. Australian Clinical trials Registry ACTRNO12605000676617.

Objectives: This study examined the relationship between older adults’ expectations to move and actual residential relocation in the community or to a nursing facility within 2 years. Method: Two waves of data (2000, 2002) from the Health and Retirement Study were used to compare expectations with subsequent moves. Logistic regression techniques were used to analyze the association between decision outcomes and expectations to move, health and functioning, physical environment, informal supports, and formal services. Results: Findings indicated that expectations to move did predict community-based moves but did not predict moves to nursing facilities. Additional factors had significant effects but did not diminish relationships between expectations and actual moves. Discussion: Results support the residential decision process as a dynamic one based on the cumulative effect of factors from an ecological model. Findings will inform policy makers and practitioners as they work to support older adults’ preferences to remain living in their homes.

Renal cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) regulate sodium transport and blood pressure. Although endothelial CYP-derived EETs are potent vasodilators, their contribution to the regulation of blood pressure remains unclear. Consequently, we developed transgenic mice with endothelial expression of the human CYP2J2 and CYP2C8 epoxygenases to increase endothelial EET biosynthesis. Compared to wild-type littermate controls, an attenuated afferent arteriole constrictor response to endothelin-1 and enhanced dilator response to acetylcholine was observed in CYP2J2 and CYP2C8 transgenic mice. CYP2J2 and CYP2C8 transgenic mice demonstrated modestly, but not significantly, lower mean arterial pressure under basal conditions compared to wild-type controls. However, mean arterial pressure was significantly lower in both CYP2J2 and CYP2C8 transgenic mice during coadministration of N-nitro-l-arginine methyl ester and indomethacin. In a separate experiment, a high-salt diet and subcutaneous angiotensin II was administered over 4 wk. The angiotensin/high-salt-induced increase in systolic blood pressure, proteinuria, and glomerular injury was significantly attenuated in CYP2J2 and CYP2C8 transgenic mice compared to wild-type controls. Collectively, these data demonstrate that increased endothelial CYP epoxygenase expression attenuates afferent arteriolar constrictor reactivity and hypertension-induced increases in blood pressure and renal injury in mice. We conclude that endothelial CYP epoxygenase function contributes to the regulation of blood pressure.—Lee, C. R., Imig, J. D., Edin, M. E., Foley, J., DeGraff, L. M., Bradbury, J. A., Graves, J. P., Lih, F. B., Clark, J., Myers, P., Perrow, A. L., Lepp, A. N., Kannon, M. A., Ronnekleiv, O. K., Alkayed, N. J., Falck, J. R., Tomer, K. B., Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice.

OBJECTIVE. The number of functionally impaired drivers being assessed is increasing the urgency to develop a standardized off-road driver assessment battery. We examined the validity of the Road Law and Road Craft Test (RLRCT) and a version of the Melbourne Slide Test to determine whether they should be included in the Occupational Therapy Driver Off-Road Assessment (OT–DORA) battery, which is under development. METHOD. We conducted a file audit of 118 data sets with individual item scores for the RLRCT and Melbourne Slide Test. RESULTS. The RLRCT test with one item removed provides clinicians with a valid indication of clients’ off-road driving skills. The Melbourne Slide Test added no new information over that provided by the RLRCT and can be excluded from the battery. CONCLUSION. The revised 14-item RLRCT should be included in the OT–DORA battery. Further research is required to develop the OT–DORA battery as a valid and reliable measure of off-road driver skill.