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Background: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell proliferation, and apoptosis.Methods: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic-euglycemic clamp study. The primary end point was a change in the level of glycated hemoglobin, and secondary end points were changes in beta-cell function, insulin sensitivity, and inflammatory markers.Results: At 13 weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage point lower than in the placebo group (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels, and the body-mass index were similar in the two study groups. Symptomatic hypoglycemia was not observed, and there were no apparent drug-related serious adverse events.Conclusions: The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation. (ClinicalTrials.gov number, NCT00303394 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]

Objectives: To establish recommendations for designing, delivering, evaluating, and reporting exercise intervention research to improve fitness-related outcomes in people living with spinal cord injury (PwSCI)., Design: International consensus process., Setting: (1) An expert panel was established consisting of 9 members of the governing panel of the International Spinal Cord Society Physical Activity Special Interest Group and 9 additional scientists who authored or co-authored ≥1 exercise randomized controlled trial paper involving PwSCI. (2) We invited the panelists to draft an outline of the recommendations for 1 intervention component. (3) The panel reviewed the draft outlines and determined whether they fit the scope and objectives of the project, whether they were evidence-based, and whether they were sufficiently detailed. (4) We interviewed 7 PwSCI who had participated in ≥1 exercise trial to gather insights on their experiences within the trials, what they liked, and what they would change. (5) A first draft of the recommendations was approved by the panel and circulated to the general members of the International Spinal Cord Society Physical Activity Special Interest Group to gather their suggestions and opinions via an online survey. (6) The member feedback was used to revise the recommendations and panel members approved a final version., Participants: N/A., Interventions: N/A., Main Outcome Measure(s): N/A., Results: We generated 33 recommendations regarding participant recruitment, study sample size determination, outcome measurement, potential confounders, exercise intervention prescription and delivery, supporting adherence to the intervention, monitoring and reporting adherence and retention, fidelity of the delivery of the intervention, monitoring and reporting adverse events, study design, and registration of study protocol and preparation of a protocol paper., Conclusions: International experts have come to consensus on recommendations for conducting exercise intervention research involving PwSCI. Adopting these recommendations will increase the quality of the research and the overall certainty of the evidence regarding the effects of exercise on health outcomes in PwSCI., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The cardiovascular benefits of surgical repair in pectus excavatum (PEx) continue to be debated, with limited data supporting repair in adult patients. Hepatic vein flow is used to identify right-sided diastolic dysfunction in cardiovascular disorders, including tricuspid stenosis, cardiac tamponade, and constrictive pericarditis. This study evaluates the effects of cardiac compression on diastolic function (as assessed by hepatic vein flow patterns and velocities) before and after repair of PEx., Methods: A retrospective study was performed of intraoperative transesophageal echocardiograms including hepatic vein assessments of adult patients who underwent preoperative and postoperative evaluations during repair of PEx from 2018 to 2021., Results: In total, 127 patients were included (median age, 29.0 [15.4] years; median Haller index, 4.2 [1.7]; 60.6% male). Statistically significant improvements were seen after pectus repair of right ventricular stroke volume and diastolic function as measured by increased postoperative velocities for hepatic vein waves ( P < .001 for all comparisons). Preoperatively, 5.5% of patients had constrictive-like physiology with end-diastolic retrograde flow that normalized postoperatively ( P  = .016). Approximately 10% of patients changed their pattern of hepatic vein flow after surgical procedure. Patients with more proximal cardiac compression had greater improvements in hepatic vein velocities after repair., Conclusions: Surgical relief of cardiac compression resulted in an immediate improvement in hepatic vein flow and right ventricle stroke volume in patients with PEx. These results support diastolic dysfunction in a large number of patients, with improvement in function and compliance after the surgical relief of cardiac compression., (© 2023 The Authors.)

Importance: Anthracyclines increase the risk for congestive heart failure (CHF); however, long-term cumulative incidence and risk factors for CHF after anthracycline therapy are not well defined in population-based studies., Objective: To compare the long-term cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracycline therapy compared with healthy controls from the same community., Design, Setting, and Participants: This retrospective population-based case-control study included data from the Rochester Epidemiology Project. Participants included residents of Olmsted County, Minnesota, diagnosed with breast cancer or lymphoma from January 1985 through December 2010 matched for age, sex, and comorbidities with healthy controls, with a final ratio of 1 case to 1.5 controls. Statistical analysis was performed between July 2017 and February 2022., Exposures: Cancer treatment and CHF risk factors., Main Outcomes and Measures: The main outcome was new-onset CHF, as defined by the modified Framingham criteria. Cox proportional hazards regression was used to estimate hazard ratios (HRs) to compare the risk of CHF in participants with cancer vs controls, adjusted for age, sex, diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and smoking history., Results: A total of 2196 individuals were included, with 812 patients with cancer and 1384 participants without cancer. The mean (SD) age was 52.62 (14.56) years and 1704 participants (78%) were female. Median (IQR) follow-up was 8.6 (5.2-13.4) years in the case group vs 12.5 (8.7-17.5) years in the control group. Overall, patients with cancer had higher risk of CHF compared with the control cohort even after adjusting for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking status (HR, 2.86 [95% CI, 1.90-4.32]; P < .001). After adjusting for the same variables, CHF risk was greater for patients with cancer receiving anthracycline (HR, 3.25 [95% CI, 2.11-5.00]; P < .001) and was attenuated and lost statistical significance for patients with cancer not receiving anthracyclines (HR, 1.78 [95% CI, 0.83-3.81]; P = .14). Higher cumulative incidence for patients treated with anthracyclines vs comparator cohort was observed at 1 year (1.81% vs 0.09%), 5 years (2.91% vs 0.79%), 10 years (5.36% vs 1.74%), 15 years (7.42% vs 3.18%), and 20 years (10.75% vs 4.98%) (P < .001). There were no significant differences in risk of CHF for patients receiving anthracycline at a dose of less than 180 mg/m2 compared with those at a dose of 180 to 250 mg/m2 (HR, 0.54 [95% CI, 0.19-1.51]) or at a dose of more than 250 mg/m2 (HR, 1.23 [95% CI, 0.52-2.91]). At diagnosis, age was an independent risk factor associated with CHF (HR per 10 years, 2.77 [95% CI, 1.99-3.86]; P < .001)., Conclusions and Relevance: In this retrospective population-based case-control study, anthracyclines were associated with an increased risk of CHF early during follow-up, and the increased risk persisted over time. The cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracyclines at 15 years was more than 2-fold that of the control group.

Background: Knowledge of the prevalence and socio-demographic characteristics of physical impairments is limited. This study aimed to determine the prevalence of physical impairments among adults in Denmark, both in total and according to nine common diagnostic subgroups, describe the socio-demographic and socio-economic profile, and compare the data with those of the general adult population., Methods: This descriptive, cross-sectional, register-based study evaluated the general socio-demographic and socio-economic variables, including sex, age, geographical region, origin, educational level, occupation, marital status, and disability level, of adults with physical impairments extracted by diagnosis from the Danish National Patient Register and Statistics Denmark by 31 December 2018. These data were compared with those of the general adult population in Denmark extracted from Statistics Denmark by January 2019., Results: In total, 606,857 adults with physical impairments were identified. Of the nine selected diagnoses, osteoarthritis (69.4%) was the most prevalent, followed by acquired brain injury (29.0%), rheumatoid arthritis (6.7%), multiple sclerosis (2.6%), spinal cord injury (1.5%), cerebral palsy (1.2%), amputation (0.7%), muscular dystrophy (0.5%), and poliomyelitis (< 0.1%). There were large variations in the socio-demographic and socio-economic profile between the nine diagnostic subgroups. The adults with physical impairments were more often women, were older, were less often immigrants and employed adults, had a lower educational level, and were more commonly married than the general adult population. Only the geographical region did not differ., Conclusion: The nine subgroups with diagnoses related to the musculoskeletal system represent 13% of the adult Danish population. The socio-demographic and socio-economic profile varied largely between the nine diagnostic subgroups, and almost all variables differed significantly between adults with physical impairments and the general adult population in Denmark. These findings reveal patterns and trends on socio-demographic and socio-economic variables essential for future planning at a societal level, including the healthcare and social sectors., (© 2022. The Author(s).)

Objective: To develop a feasible protocol for testing maximum shoulder rotation strength in tetraplegic wheelchair athletes, and investigate concurrent validity of maximum isometric handheld dynamometer (HHD) towards maximum isokinetic dynamometer (ID) strength measurements; secondly, to study shoulder muscle activation during maximum shoulder rotation measurements, and the association between shoulder strength and shoulder pain. Design: Descriptive methodological. Setting: Danish Wheelchair Rugby (WCR) association for WCR tetraplegic athletes from local WCR-clubs. Participants: Twelve adult tetraplegics. Interventions: N/A. Outcome measures: Wheelchair User's Shoulder Pain Index (WUSPI) and Visual Analog Scale (VAS) measured shoulder pain, isometric HHD and ID (60°/s) measured maximum internal (IR) and external (ER) shoulder rotation strength. Surface Electromyography normalized to maximum EMG measured muscle activity (mm Infraspinatus and Latissimus Dorsi) during maximum shoulder rotation strength. Results: Concurrent validity of isometric HHD towards ID showed Concordance Correlation Coefficients of left and right arms 0.90 and 0.86 (IR), and 0.89 and 0.91 (ER), with no difference in muscle activity between isometric HHD and ID, but larger co-activation during ER. There was no association between shoulder strength and pain, except for significantly weak negative associations between ID and pain during ER for left and right arms (P   = 0.03; P   = 0.04). Conclusion: Standardized feasible protocol for tetraplegic wheelchair athletes for measuring maximum shoulder rotation strength was established. Isometric HHD is comparable with ID on normalized peak torques and muscle activity, but with larger co-activation. Strength was not clearly associated with shoulder pain.

Although infrequent, damage to cardiovascular structures can occur during or following a minimally invasive repair of pectus excavatum. We present a case of right ventricular outflow tract compression caused by a displaced intrathoracic bar. Removal of the bar resulted in an improvement in symptoms and hemodynamics. ( Level of Difficulty: Advanced. )., Competing Interests: Dr Jaroszewski has served as a consultant for Zimmer Biomet, Inc; and has received IP/royalty rights under Mayo Clinic Ventures with Zimmer Biomet, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Study Design: Systematic review and meta-analysis OBJECTIVES: The objective was to summarise prior research regarding the efficacy of active physiotherapy interventions and prevention strategies on shoulder pain, decreased physical function and quality of life in people with a spinal cord injury (SCI)., Methods: A systematic literature search was conducted in CENTRAL, EMBASE (via Ovid), CINAHL and MEDLINE (via Ovid). Randomised controlled trials investigating effects of active physiotherapy interventions on shoulder pain, physical function and quality of life were included. Further, prospective cohort studies investigating effects of active physiotherapy interventions in prevention of shoulder pain and reduced physical function were included. Mean difference (MD) for pain (15 items on a 0-10 scale) and standardised mean difference (SMD) for physical function were summarised in a random effects meta-analysis., Results: Four studies on treatment (totalling 167 participants), and no studies on prevention were included. Significant and clinically meaningful improvements on shoulder pain (MD 19.06, 95% CI 5.72-32.40; I 2  = 65%) (scale 0-150) and physical function (SMD 0.61, 95% CI 0.27-0.94; I 2  = 0%) were found for active physiotherapy interventions. Only one study included quality of life, making meta-analysis inappropriate., Conclusions: Evidence from a sparse number of studies supports active physiotherapy interventions to decrease shoulder pain and increase physical function in people with SCI who use a manual wheelchair. No studies met the criteria for prevention, highlighting a lack of research investigating prevention of shoulder pain and decreased physical function and quality of life., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

Prolactin and placental lactogens increase during pregnancy and are involved with many aspects of maternal metabolic adaptation to pregnancy, likely to impact on fetal growth. The aim of this study was to determine whether maternal plasma prolactin or placental lactogen concentrations at 20 weeks of gestation were associated with later birth of small-for-gestational-age babies (SGA). In a nested case-control study, prolactin and placental lactogen in plasma samples obtained at 20 weeks of gestation were compared between 40 women who gave birth to SGA babies and 40 women with uncomplicated pregnancies and size appropriate-for-gestation-age (AGA) babies. Samples were collected as part of the 'screening of pregnancy endpoints' (SCOPE) prospective cohort study. SGA was defined as birthweight <10th customized birthweight centile (adjusted for maternal weight, height, ethnicity, parity, infant sex, and gestation age) in mothers who remained normotensive. No significant differences were observed in concentrations of prolactin or placental lactogen from women who gave birth to SGA babies compared with women with uncomplicated pregnancies. However, a sex-specific association was observed in SGA pregnancies, whereby lower maternal prolactin concentration at 20 weeks of gestation was observed in SGA pregnancies that were carrying a male fetus (132.0 ± 46.7 ng/mL vs 103.5 ± 38.3 ng/mL, mean ± s.d., P  = 0.036 Student's t -test) compared to control pregnancies carrying a male fetus. Despite the implications of these lactogenic hormones in maternal metabolism, single measurements of either prolactin or placental lactogen at 20 weeks of gestation are unlikely to be useful biomarkers for SGA pregnancies., Lay Summary: Early identification during pregnancy of small for gestational age (SGA) babies would enable interventions to lower risk of complications around birth (perinatal), but current detection rates of these at risk babies is low. Pregnancy hormones, prolactin and placental lactogen, are involved in metabolic changes that are required for the mother to support optimal growth and development of her offspring during pregnancy. The levels of these hormones may provide a measurable indicator (biomarker) to help identify these at risk pregnancies. Levels of these hormones were measured in samples from week 20 of gestation from women who went on to have SGA babies and control pregnancies where babies were born at a size appropriate for gestation age. Despite the implications of prolactin and placental lactogen in maternal metabolism, no significant differences were detected suggesting that single measures of either prolactin or placental lactogen at 20 weeks gestation are unlikely to be useful biomarker to help detect SGA pregnancies., (© The authors.)

Study Design: Cross-sectional study., Objectives: To describe the socio-demographics, injury characteristics, prevalence of shoulder and neck symptoms, weekly participation in leisure time physical activity (LTPA) and quality of life (QoL) of individuals with spinal cord injury in Denmark (SCI)., Setting: Nation-wide community survey, Denmark., Methods: Individuals with SCI for >2 years were included from three SCI rehabilitation departments. Questionnaire data regarding socio-demographic details, SCI injury characteristics, medical history, shoulder and neck symptoms, LTPA and QoL were collected., Results: Of 2454 potential participants, 1517 (62%) responded to the survey (mean age = 56.2, SD 16.1, 37% female, 42% tetraplegia, 23% complete SCI, mean time since injury = 16.9, SD 13.5). 75% used some form of assistive mobility device. Responders and non-responders showed no sex or injury type/severity differences. Shoulder and neck symptoms within the past 3 months were reported by 63 and 67% respectively, with 51% reporting shoulder symptoms within the past week. Among those with symptoms, 61% had experienced shoulder symptoms and 56% neck symptoms, for more than 30 days during the previous 3 months. Symptoms often prevented participants from performing their usual activities (due to shoulder symptoms 46%, neck symptoms 41%)., Conclusions: A high prevalence of self-reported shoulder and neck symptoms was found, which may limit physical function and social activities. We succeeded in generating the Danish Spinal Cord Injury Shoulder (DanSCIS) dataset, which comprised a substantial proportion of Danish adults with SCI. Future studies using data from this cohort will investigate patterns and associations between shoulder/neck symptoms, use of assistive mobility devices, LTPA and QoL.

Introduction: In the developing phase of the complex health intervention: Physical Activity to reduce Vascular Erectile Dysfunction (PAVED), it is crucial to explore whether men can accept the communicative component regarding information that regular aerobe Physical Activity can reduce Erectile Dysfunction (i-PAVED). This information is provided by health professionals (HPs) in cardiac rehabilitation, where sexuality issues such as erectile dysfunction (ED) are otherwise rarely addressed., Aim: To explore how acceptance of cardiac HPs' address of sexuality, ED, and i-PAVED can be identified in men's narratives., Methods: In this descriptive qualitative study, we conducted semi-structured individual interviews with 20 men (range 48-78 years of age) attending municipal cardiac secondary prevention and rehabilitation programmes on their acceptance of HPs' address of sexuality, ED, and i-PAVED. The Theoretical Framework of Acceptability components (affective attitude, burden, ethicality, intervention coherence, perceived effectiveness, opportunity costs and self-efficacy) and three temporal perspectives (retrospective, concurrent and prospective) were used in the concept-driven first step of a content analysis, which was followed by a thematically data-driven second step., Main Outcome Measures: Men anticipated and experiential acceptance was identified in six out of seven components of Theoretical Framework of Acceptability., Results: Men acceptance was identified as "expression of interest," "addressing sexuality," "attitudes and values," "understandable and meaningful," "insights" and "motivation," whereas no narratives were identified in relation to the component of opportunity costs., Conclusion: As an aspect of the development of the complex cardiovascular health care intervention PAVED, this qualitative study showed that men attending cardiac secondary prevention and rehabilitation seemed to prospectively accept the communicative component of PAVED being HPs' address of sexuality, ED, and i-PAVED, if the HPs are professional, educated and competent in the field of sexual health. Gerbild H, Areskoug-Josefsson K, Larsen CM, et al. Acceptability of Health Professionals' Address of Sexuality and Erectile Dysfunction - A Qualitative Interview Study with Men in Cardiac Rehabilitation. Sex Med 2021;9:100369., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Danish health professional (HP) students' attitudes toward addressing sexual health are unknown., Aim: To investigate Danish HP students' attitudes toward addressing sexual health in their future professions, and to assess differences in perceived competences and preparedness between professional programs., Methods: A Danish national survey of nursing, occupational therapy, and physiotherapy students was conducted. Totally, 1,212 students were invited to respond to an online questionnaire "The Students' Attitudes toward Addressing Sexual Health.", Main Outcome Measure: The main outcome measures investigated were Danish HP students' attitudes toward addressing sexual health in their future professions, and differences in perceived competences and preparedness depending on the professional program., Results: A total of 584 students (48%; nursing 44%, occupational therapy 70%, physiotherapy 43%) responded. Mean total score ranged between 63.7 and 66.3 (±8.3-8.8) classifying students in the low-end of the class: "comfortable and prepared in some situations." No clinically relevant differences were determined between the professional programs with respect to perceived competences and preparedness to address sexual health., Conclusion: In the field of addressing sexual health, most Danish HP students reported positive attitudes and a need for basic knowledge, competences, communication training, and education. H Gerbild, C M Larsen, T. Junge, B. S. Laursen, K. Areskoug-Josefsson. Danish Health Professional Students' Attitudes Toward Addressing Sexual Health: A Cross-Sectional Survey. Sex Med 2021;9:100323., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction : The aim of this study was to assess the inter-rater reliability of selected static, semi-dynamic, and dynamic test assessment methods for evaluation of scapular positioning and function. Methods : A standardized three-phase (i.e. training, overall agreement, and actual study) protocol for reliability studies was applied on 41 overhead sports participants, aged 18-56 (22 with obvious scapular winging, classified as visibility of the medial or inferior angle border of scapula). Ten scapular test assessment methods (two static, three semi-dynamic, and five dynamic) were evaluated. Results : Bland-Altman plots showed no funnel effects, although systematic bias and significant differences between raters were present in three of the methods. ICC values ranged from 0.71 to 0.80 for the static test assessment methods and from 0.25-0.92 for the semi-dynamic test assessment methods. Three of the five dynamic test assessment methods had ICCs of 0.47-0.68. For the two remaining dynamic test assessment methods, kappa varied between -0.034 and 0.71. Using PABAK, kappa increased to 0.54-0.86. Conclusion : Four scapular test assessment methods (Upper horizontal distance, Lower horizontal distance at max shoulder flexion, Acromial distance, and Winging scapula) showed satisfactory inter-rater reliability. Simple visual observational methods and quantitative distance measurements have better reliability between clinicians than more complex measurements and may be better suited for use in clinical practice.

Objectives: To determine the attitudes of eldercare services managers to the potential health benefits of workplace health promotion programmes (WHPPs), including physical exercise during working hours and the feasibility of implementing a WHPP at the workplace., Study Design: A cross-sectional study., Methods: Respondents filled out a 14-item questionnaire on attitudes towards the potential health benefits of WHPPs and the feasibility of implementing WHPPs. Differences between groups were analysed using the Kruskal-Wallis test. The significance level was set to p ​= ​0.05. Bonferroni's correction was used in the setting of multiple comparisons. A content analysis was performed exploring answers provided in the optional comment section in the questionnaire., Results: 695 eldercare services managers in Denmark were contacted by email, 393 replied, and 382 respondents were included in the analysis (54.7%). The survey revealed that 89.8% of the respondents believed that WHPPs would increase health, 89.6% believed that it would increase well-being and 87.6% believed that WHPPs would increase workability among workers. 87.7% expressed a willingness towards implementing WHPPs and believed 'it to be a good idea'. Respondents with a negative attitude to the feasibility of implementing WHPPs, were more likely to hold negative attitudes to the potential health benefits of WHPPs (p ​< ​0.001). Organisational issues were the most frequently stated barrier to implementation., Conclusions: The majority of eldercare managers expressed a positive attitude to the benefits of WHPPs and their implementation. Addressing organisational issues and ensuring management support in the planning stage of a WHPP is highly important., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Staphylococcus aureus is an opportunistic pathogen associated with soft-tissue infections commonly encountered in indoor and farm environments as a component of airborne dust, which can potentially deposit in the respiratory tracts of workers and residents. However, knowledge regarding the survival and inflammatory potential of S. aureus in airborne dust has not been described. The objective of this study was to obtain knowledge on whether the presence of dust during aerosolisation affects the culturability (ability to grow on agar plates), their biofilm forming capacity, viability (using a viability qPCR), and inflammatory potential (using a human granulocyte based assay), and whether time from aerosolisation to subsequent analyses (the resting time) affects these. Aerosols containing S. aureus (DSM6148) in the presence of sterilised airborne dust from a pig farm were found to have higher culturability, viability, inflammatory potential, and ability to form biofilm compared with S. aureus aerosols generated without airborne dust. When aerosols of S. aureus were generated without dust, they showed a reduction in the culturability, as well as the biofilm forming capacity and an extended resting time was associated with a reduction in culturability, and biofilm forming capacity. In contrast, no differences in the viability were observed in samples with different resting times. The lack of a significant effect of different resting times on viability, and the significant effect on culturability, suggests that the stresses of aerosolisation may induce a viable, but not culturable (VBNC) state in S. aureus. A synergistic effect was found between S. aureus and dust concerning their ability to induce inflammation. In conclusion presence of airborne dust during aerosolisation of S. aureus affects the culturability, biofilm forming capacity, and inflammatory potential, but not the viability of S. aureus. This is of importance in relation to hygiene as well as how exposure to S. aureus is measured., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: The aim was to investigate the effect of Electromyography (EMG)-biofeedback guided exercises (BIONEX) on shoulder pain and function in participants with subacromial pain syndrome (SPS)., Methods: Twenty-five women and 24 men (19-67 years), diagnosed with SPS, were randomised to BIONEX or the same exercises without EMG-biofeedback (NEX). Primary outcome was shoulder pain during the past 7 days (Numeric Pain Rating Scale (NPRS)). Secondary outcomes included self-reported (Disability of Arm Shoulder and Hand (DASH), Oxford Shoulder Score (OSS)), and measured shoulder function (surface EMG from upper trapezius, lower trapezius and serratus anterior) in mean and ratios of % of maximum voluntary EMG (%MVE) and onset time (msec), during arm tasks with 0, 1 and 3 kg., Results: There was no group difference (BIONEX versus NEX) in changed shoulder pain (NPRS, mean difference 0.18 (95% CI. -1.56; 1.19)), self-reported or measured shoulder function. Both groups, however, showed significant within-group improvements on self-reported outcomes (NPRS, DASH, OSS), only clinically relevant on NPRS (BIONEX 2.23 (SD 2.47); NEX 2.04 (SD 2.29))., Conclusion: BIONEX and NEX were both effective in reducing pain to a clinically relevant level, while EMG-biofeedback did not make a difference. The current neuromuscular shoulder exercise protocol is recommended., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: This scoping review aims to gather and map inspiration, ideas and recommendations for teaching evidence-based practice across Professional Bachelor Degree healthcare programmes by mapping literature describing evidence-based practice teaching methods for undergraduate healthcare students including the steps suggested by the Sicily Statement., Methods: A computer-assisted literature search using PubMed, Cinahl, PsycINFO, and OpenGrey covering health, education and grey literature was performed. Literature published before 2010 was excluded. Students should be attending either a Professional Bachelor's degree or a Bachelor's degree programme. Full-text articles were screened by pairs of reviewers and data extracted regarding: study characteristics and key methods of teaching evidence-based practice. Study characteristics were described narratively. Thematic analysis identified key methods for teaching evidence-based practice, while full-text revisions identified the use of the Sicily Statement's five steps and context., Results: The database search identified 2220 records. One hundred ninety-two records were eligible for full-text assessment and 81 studies were included. Studies were conducted from 2010 to 2018. Approximately half of the studies were undertaken in the USA. Study designs were primarily qualitative and participants mainly nursing students. Seven key methods for teaching evidence-based practice were identified. Research courses and workshops, Collaboration with clinical practice and IT technology were the key methods most frequently identified. Journal clubs and Embedded librarians were referred to the least. The majority of the methods included 2-4 of the Sicily Statement's five steps, while few methods referred to all five steps., Conclusions: This scoping review has provided an extensive overview of literature describing methods for teaching EBP regarding undergraduate healthcare students. The two key methods Research courses and workshops and Collaboration with clinical practice are advantageous methods for teaching undergraduate healthcare students evidence-based practice; incorporating many of the Sicily Statement's five steps. Unlike the Research courses and workshop methods, the last step of evaluation is carried out partly or entirely in a clinical context. Journal clubs and Embedded librarians should be further investigated as methods to reinforce existing methods of teaching. Future research should focus on methods for teaching EBP that incorporate as many of the five steps of teaching and conducting EBP as possible.

Vegetative insecticidal proteins (Vips) from Bacillus thuringiensis (Bt) are unique from crystal (Cry) proteins found in Bt parasporal inclusions as they are secreted during the bacterial vegetative growth phase and bind unique receptors to exert their insecticidal effects. We previously demonstrated that large modifications of the Vip3 C-terminus could redirect insecticidal spectrum but results in an unstable protein with no lethal activity. In the present work, we have generated a new Vip3 protein, Vip3Ab1-740, via modest modification of the Vip3Ab1 C-terminus. Vip3Ab1-740 is readily processed by midgut fluid enzymes and has lethal activity towards Spodoptera eridania , which is not observed with the Vip3Ab1 parent protein. Importantly, Vip3Ab1-740 does retain the lethal activity of Vip3Ab1 against other important lepidopteran pests. Furthermore, transgenic plants expressing Vip3Ab1-740 are protected against S. eridania , Spodoptera frugiperda , Helicoverpa zea , and Pseudoplusia includens . Thus, these studies demonstrate successful engineering of Vip3 proteins at the C-terminus to broaden insecticidal spectrum, which can be employed for functional expression in planta.

Vip3A proteins are important for the control of spodopteran pests in crops, including Spodoptera frugiperda (fall armyworm). Native Vip3Ab1 controls S. frugiperda , but it is ineffective against S. eridania (southern armyworm), a major pest of soybean in South America. Recently, a Vip3Ab1 chimera with a modified C-terminus was described, Vip3Ab1-740, which has increased potency against S. eridania while maintaining activity against S. frugiperda . As S. frugiperda and S. eridania are differentially susceptible to Vip3Ab1, experiments were conducted to identify and understand the mechanism by which this expanded potency is conferred. The role of protein stability, processing, and in vivo effects of Vip3Ab1 and Vip3Ab1-740 in both of these species was investigated. Biochemical characterization of the midgut fluids of these two species indicated no obvious differences in the composition and activity of digestive enzymes, which protease inhibitor studies indicated were likely serine proteases. Histological examination demonstrated that both proteins cause midgut disruption in S. frugiperda , while only Vip3Ab1-740 affects S. eridania . Immunolocalization indicated that both proteins were present in the midgut of S. frugiperda , but only Vip3Ab1-740 was detected in the midgut of S. eridania . We conclude that the gain of toxicity of Vip3Ab1-740 to S. eridania is due to an increase in protein stability in the midgut, which was conferred by C-terminal modification.

Background: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder with a high mortality. Clinical experience and small case series suggest thrombocytopenia may be frequent in this population and associated with a poor prognosis. We sought to estimate the prevalence of thrombocytopenia in patients with PAH and characterize its association with disease characteristics and patient outcome., Methods: Single center cohort study of 714 incident adult patients with Group 1 PH who were evaluated for baseline platelet count at the time of diagnosis. Pts were stratified into three groups: normal platelet count (>150 × 10 9 /L), Grade 1 thrombocytopenia (75-149 × 10 9 /L) and Grade 2-4 thrombocytopenia (<75 × 10 9 /L)., Results: The median platelet count was 209 × 10 9 /L (IQR 163, 264). There were 572 (80%) pts without thrombocytopenia, 107 (15%) with Grade 1 and 35 (5%) with Grade 2-4 thrombocytopenia. The median pt age was 55 years (IQR 44-65) with no difference between platelet groups (p = 0.85). Men were more likely to have thrombocytopenia (62, 34%) than women (80, 15%, p < 0.0001). Thrombocytopenia was frequent with portopulmonary PAH (84%) as opposed to idiopathic PAH (iPAH; 14%) or connective tissue disease associated PAH (12%). Platelet counts were not associated with functional class symptoms, the degree of right ventricular enlargement or dysfunction or tricuspid regurgitation by echocardiography. Invasive hemodynamics of right atrial pressure, mean pulmonary artery pressure and pulmonary vascular resistance were also similar between platelet groups. Thrombocytopenia was associated with higher mortality in iPAH patients (age- and sex-adjusted 5 year mortality [HR 1.95 (1.20, 3.08) p = 0.008] but not in other etiology groups. In a multivariate model of iPAH patients (adjusted for age, sex, DLCO, PVR, creatinine and 6MW distance) thrombocytopenia was most predictive of 5-year mortality [HR 1.68 (1.32, 2.12), p < 0.0001]., Conclusion: Thrombocytopenia in the context of iPAH portends a poor prognosis and is a simple independent factor to consider in judging severity of disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no financial conflicts of interest.

Introduction: The leading cause of erectile dysfunction (ED) is arterial dysfunction, with cardiovascular disease as the most common comorbidity. Therefore, ED is typically linked to a web of closely interrelated cardiovascular risk factors such as physical inactivity, obesity, hypertension, and metabolic syndrome. Physical activity (PA) has proved to be a protective factor against erectile problems, and it has been shown to improve erectile function for men affected by vascular ED. This systematic review estimated the levels of PA needed to decrease ED for men with physical inactivity, obesity, hypertension, metabolic syndrome, and/or manifest cardiovascular diseases., Aim: To provide recommendations of levels of PA needed to decrease ED for men with physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases., Methods: In accord with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed of research articles specifically investigating PA as a possible treatment of ED. The review included research on ED from physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases. All available studies from 2006 through 2016 were checked for the predetermined inclusion and exclusion criteria to analyze the levels of PA needed to decrease ED., Results: 10 articles met the inclusion criteria, all suggesting various levels of PA needed to decrease ED for men with relevant risk factors for ED. The results of the review provided sufficient research evidence for conclusions regarding the levels of PA necessary to decrease ED., Conclusion: Recommendations of PA to decrease ED should include supervised training consisting of 40 minutes of aerobic exercise of moderate to vigorous intensity 4 times per week. Overall, weekly exercise of 160 minutes for 6 months contributes to decreasing erectile problems in men with ED caused by physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases. Gerbild H, Larsen CM, Graugaard C, Areskoug Josefsson K. Physical Activity to Improve Erectile Function: A Systematic Review of Intervention Studies. Sex Med 2018;6:75-89., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Tricuspid valve regurgitation (TR) is a frequent finding in patients with pulmonary arterial hypertension (PAH). However, its prognostic significance and relation to PAH, while suspected, are poorly understood. We assessed 727 consecutive patients with newly diagnosed PAH who underwent transthoracic echocardiographic evaluation of tricuspid valve function., Objectives: The study objective was to determine the association of TR presence and severity with patient characteristics, pulmonary artery hemodynamics and outcome., Methods: Consecutive patients with newly diagnosed PAH (N = 727 with group 1 pulmonary hypertension) underwent transthoracic echocardiographic evaluation of tricuspid valve function at diagnosis. The primary study end point was all-cause mortality or lung transplantation., Results: In this population, 702 patients (96.5%) had TR; in 165 patients (23%), TR was severe. Compared with those with no or mild TR by echocardiography criteria, patients with severe TR had shorter mean (SD) 6-minute walk distances (285 [125] m vs 360 [121] m; P = .02) and higher levels of B-type natriuretic peptide (695 [672] pg/dL vs 328 [300] pg/dL; P < .05). Severe TR was associated with greater right atrial dilatation (91% vs 47%; P = .004) and right ventricular (RV) dilatation (92% vs 51%; P = .008), greater right atrial pressure (mean [SD] 15 [7] mm Hg vs 10 [6] mm Hg; P < .001) and lower cardiac index (mean [SD], 2.2 [0.7] L/min/m2 vs 2.8 [0.9] L/min/m2; P < .001). Severe TR was strongly predictive of greater 5-year mortality risk after adjustment for age, sex, functional class, 6-minute walk distance, diffusing capacity, RV size and pulmonary vascular resistance index (adjusted hazard ratio, 1.83; 95% CI, 1.38-2.41; P < .001)., Conclusions: Severe TR was a significant predictor of long-term mortality rate in PAH, and TR severity correlated with PAH severity., (© 2017 John Wiley & Sons Ltd.)

Objective: First, to investigate the intertester reliability of clinical shoulder instability and laxity tests, and second, to describe the mutual dependency of each test evaluated by each tester for identifying self-reported shoulder instability and laxity., Methods: A standardised protocol for conducting reliability studies was used to test the intertester reliability of the six clinical shoulder instability and laxity tests: apprehension, relocation, surprise, load-and-shift, sulcus sign and Gagey. Cohen's kappa (κ) with 95% CIs besides prevalence-adjusted and bias-adjusted kappa (PABAK), accounting for insufficient prevalence and bias, were computed to establish the intertester reliability and mutual dependency., Results: Forty individuals (13 with self-reported shoulder instability and laxity-related shoulder problems and 27 normal shoulder individuals) aged 18-60 were included. Fair (relocation), moderate (load-and-shift, sulcus sign) and substantial (apprehension, surprise, Gagey) intertester reliability were observed across tests (κ 0.39-0.73; 95% CI 0.00 to 1.00). PABAK improved reliability across tests, resulting in substantial to almost perfect intertester reliability for the apprehension, surprise, load-and-shift and Gagey tests (κ 0.65-0.90). Mutual dependencies between each test and self-reported shoulder problem showed apprehension, relocation and surprise to be the most often used tests to characterise self-reported shoulder instability and laxity conditions., Conclusions: Four tests (apprehension, surprise, load-and-shift and Gagey) out of six were considered intertester reliable for clinical use, while relocation and sulcus sign tests need further standardisation before acceptable evidence. Furthermore, the validity of the tests for shoulder instability and laxity needs to be studied., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Availability of well characterized maize regulatory elements for gene expression in a variety of tissues and developmental stages provides effective alternatives for single and multigene transgenic concepts. We studied the expression of the herbicide tolerance gene aryloxyalkanoate dioxygenase (aad-1) driven by seven different regulatory element construct designs including the ubiquitin promoters of maize and rice, the actin promoters of melon and rice, three different versions of the Sugarcane Bacilliform Badnavirus promoters in association with other regulatory elements of gene expression., Results: Gene expression of aad-1 was characterized at the transcript and protein levels in a collection of maize tissues and developmental stages. Protein activity against its target herbicide was characterized by herbicide dosage response. Although differences in transcript and protein accumulation were observed among the different constructs tested, all events were tolerant to commercially relevant rates of quizalafop-P-ethyl compared to non-traited maize under greenhouse conditions., Discussion: The data reported demonstrate how different regulatory elements affect transcript and protein accumulation and how these molecular characteristics translate into the level of herbicide tolerance. The level of transcript detected did not reflect the amount of protein quantified in a particular tissue since protein accumulation may be influenced not only by levels of transcript produced but also by translation rate, post-translational regulation mechanisms and protein stability. The amount of AAD-1 enzyme produced with all constructs tested showed sufficient enzymatic activity to detoxify the herbicide and prevent most herbicidal damage at field-relevant levels without having a negative effect on plant health., Conclusions: Distinctive profiles of aad-1 transcript and protein accumulation were observed when different regulatory elements were utilized in the constructs under study. The ZmUbi and the SCBV constructs showed the most consistent robust tolerance, while the melon actin construct provided the lowest level of tolerance compared to the other regulatory elements used in this study. These data provide insights into the effects of differing levels of gene expression and how these molecular characteristics translate into the level of herbicide tolerance. Furthermore, these data provide valuable information to optimize future designs of single and multiple gene constructs for maize research and crop improvement.

The objective of this study was to evaluate the relation between body mass index (BMI), exercise capacity, and symptoms in patients with hypertrophic cardiomyopathy (HC) and to utilize results of cardiopulmonary exercise tests (CPX) and transthoracic echocardiograms to understand the mechanism(s) of reduced exercise capacity across body mass index groups. Over a 6-year period, 510 consecutive patients with HC seen at a tertiary referral center underwent (CPX) and a transthoracic echocardiogram. Increasing BMI was associated with decreased exercise capacity as assessed by peak VO 2 (ml/kg/min). However, the prevalence of cardiac impairment did not vary by BMI group. In conclusion, these findings suggest that in some patients with hypertrophic cardiomyopathy, cardiac impairment is not the primary cause of exercise limitation and weight loss may result in improved exercise capacity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This pilot study aimed to explore if healthcare professional students participating in a 2-week elective course, Sexual Health in Rehabilitation (SHR), led to significant and sustained change in experienced competence and attitudes towards addressing sexual health in their future professions, when measured with the Students' Attitudes towards Sexual Health-Danish version (SA-SH-D). Comparison-group design, using the SA-SH-D at baseline, after the 2 weeks course and 3 months after completing the course. Participation in the SHR course significantly changed the students' attitudes; decreasing their fears of offending the patients and increasing their feelings of comfort in communicating about sexual health, and the results sustained during the follow-up period of 3 months. The results of the intervention suggest that a 2-week elective SHR course leads to sustained change healthcare students' attitudes towards addressing sexual health in their future profession. Sexual health education positively changed the students' attitudes, decreased their fears of offending the patients and increased their feelings of comfort in communicating about sexual health. The SA-SH-D is a useful tool to measure results of educational interventions aiming to change healthcare students' attitudes towards addressing sexual health in their future profession. Future research is recommended regarding students' attitudes towards addressing sexual health with persons living with disabilities. There is also a need to further research the effect of elective versus compulsory sexual health education in healthcare programs, to lessen the risk that healthcare students in their future profession will not be able to give equal care due to variation in competence and attitude., Competing Interests: Compliance with Ethical StandardsThe authors declare that they have no conflict of interest.

Guidelines recommend exercise stress echocardiogram (ESE) for patients with hypertrophic cardiomyopathy (HC) if a 50 mm Hg gradient is not present at rest or provoked with Valsalva or amyl nitrite, to direct medical and surgical management. However, no study has directly compared all 3 methods. We sought to evaluate efficacy and degree of provocation of left ventricular outflow gradients by ESE, and compare with Valsalva and amyl nitrite. In patients with HC between 2002 and 2015, resting echocardiograms and ESEs within 1 year were retrospectively reviewed. Gradients elicited by each provocation method were compared. Rest and ESE were available in 97 patients (mean age 54 ± 18 years, 57% male); 78 underwent Valsalva maneuver and 41 amyl nitrite provocation. Median gradients (interquartile range) were 10 mm Hg (7,19) at rest, 16 mm Hg (9,34) with Valsalva, 23 mm Hg (13,49) with amyl nitrite, and 26 mm Hg (13,58) with ESE. ESE and amyl nitrite were able to provoke obstruction (≥30 mm Hg) and severe obstruction (≥50 mm Hg) more frequently than Valsalva. In patients with resting gradient <30 mm Hg (n = 83), provocation maneuvers demonstrated dynamic obstruction in 51%; in those with Valsalva gradient <30 mm Hg (n = 57), ESE or amyl nitrite provoked a gradient in 44%; and in those with amyl nitrite gradient <30 mm Hg (n = 20), ESE provoked a gradient in 29%. No demographic or baseline echocardiographic parameter predicted provocable obstruction. In conclusion, ESE is clinically useful; however, different provocation maneuvers may be effective in different patients with HC, and all maneuvers may be required to provoke dynamic obstruction in symptomatic patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Subjects reporting neck/shoulder pain have been shown to generate less force during maximal voluntary isometric contractions (MVC) of the shoulder muscles compared to healthy controls. This has been suggested to be caused by a pain-related decrease in voluntary activation (VA) rather than lack of muscle mass. The aim of the present study was to investigate VA of the trapezius muscle during MVCs in subjects with and without neck/shoulder pain by use of the twitch interpolation technique. Ten cases suffering from pain and ten age and gender matched, healthy controls were included in the study. Upper trapezius muscle thickness was measured using ultrasonography and pain intensity was measured on a 100mm visual analog scale (VAS). VA was calculated from five maximal muscle activation attempts. Superimposed stimuli were delivered to the accessory nerve at peak force and during a 2% MVC following the maximal contraction. Presented as mean±SD for cases and controls, respectively: VAS; 16.0±14.4mm and 2.1±4.1mm (P=0.004), MVC; 545±161N and 664±195N (P=0.016), upper trapezius muscle thickness; 10.9±1.9mm and 10.4±1.5mm (P=0.20), VA; 93.6±14.2% and 96.3±6.0% (P=0.29). In spite of significantly eight-fold higher pain intensity and ∼20% lower MVC for cases compared to controls, no difference was found in VA. Possible explanations for the reduction in MVC could be differences in co-activation of antagonists and synergists as well as muscle quality., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to evaluate the use of a glucose meter with surgical patients under general anesthesia in the operating room., Methods: Glucose measurements were performed intraoperatively on 368 paired capillary and arterial whole blood samples using a Nova StatStrip (Nova Biomedical, USA) glucose meter and compared with 368 reference arterial whole blood glucose measurements by blood gas analyzer in 196 patients. Primary outcomes were median bias (meter minus reference), percentage of glucose meter samples meeting accuracy criteria for subcutaneous insulin dosing as defined by Parkes error grid analysis for type 1 diabetes mellitus, and accuracy criteria for intravenous insulin infusion as defined by Clinical and Laboratory Standards Institute guidelines. Time under anesthesia, patient position, diabetes status, and other variables were studied to determine whether any affected glucose meter bias., Results: Median bias (interquartile range) was -4 mg/dl (-9 to 0 mg/dl), which did not differ from median arterial meter bias of -5 mg/dl (-9 to -1 mg/dl; P = 0.32). All of the capillary and arterial glucose meter values met acceptability criteria for subcutaneous insulin dosing, whereas only 89% (327 of 368) of capillary and 93% (344 of 368) arterial glucose meter values met accuracy criteria for intravenous insulin infusion. Time, patient position, and diabetes status were not associated with meter bias., Conclusions: Capillary and arterial blood glucose measured using the glucose meter are acceptable for intraoperative subcutaneous insulin dosing. Whole blood glucose on the meter did not meet accuracy guidelines established specifically for more intensive (e.g., intravenous insulin) glycemic control in the acute care environment.

Background and Purpose: The 6-minute walk test (6MWT) is widely used as a clinical outcome measure. However, the reliability of the 6MWT is unknown in individuals who have recently experienced a hip fracture. The aim of this study was to evaluate the relative and absolute interrater reliability of the 6MWT in individuals with hip fracture., Methods: Two senior physical therapy students independently examined a convenience sample of 20 participants in a randomized order. Their assessments were separated by 2 days and followed the guidelines of the American Thoracic Society. Hip fracture-related pain was assessed with the Verbal Ranking Scale., Results: Participants (all women) with a mean (standard deviation) age of 78.1 (5.9) years performed the test at a mean of 31.5 (5.8) days postsurgery. Of the participants, 10 had a cervical fracture and 10 had a trochanteric fracture. Excellent interrater reliability (intraclass correlation coefficient [ICC2.1] = 0.92; 95% confidence interval, 0.81-0.97) was found, and the standard error of measurement and smallest real difference were calculated to be 21.4 and 59.4 m, respectively. Bland-Altman plots revealed no significant difference (mean of 3.2 [31.5] m, P = .83) between the 2 raters, and no heteroscedasticity was observed (r = -0.196, P = .41). By contrast, participants walked an average of 21.7 (22.5) m longer during the second trial (P = .002). Participants with moderate hip fracture-related pain walked a shorter distance than those with no or light pain during the first test (P = .04), but this was not the case during the second test (P = .25)., Conclusion: The interrater reliability of the 6MWT is excellent, and changes of more than 21.4 m (group level) and 59.4 m (individual participants with hip fracture) indicate a real change in the 6MWT. Measuring hip fracture-related pain during testing is recommended for individuals with hip fracture who undergo the 6MWT.

Cardio-oncology is a rapidly growing field aimed at minimizing the effects of cardiovascular morbidity and mortality in cancer survivors. To meet this aim, patients are assessed at baseline to define their risk of cardiotoxicity and then followed closely during and after chemotherapy to assess for early signs or symptoms of cardiovascular disease. Cardiac imaging, and in particular, transthoracic echocardiography, plays an essential role in the baseline assessment and serial follow-up of cardio-oncology patients. The objectives of this paper are to review the mechanisms of cardiotoxicity of several common chemotherapeutic agents associated with an increased risk for left ventricular systolic dysfunction and to outline recommendations regarding the baseline assessment and serial follow-up of cardio-oncology patients with a focus on the role of echocardiography., (© 2017 The authors.)

Unlabelled: Tuberoinfundibular dopamine (TIDA) neurons, known as neuroendocrine regulators of prolactin secretion from the pituitary gland, also release GABA within the hypothalamic arcuate nucleus. As these neurons express prolactin receptors (Prlr), prolactin may regulate GABA secretion from TIDA neurons, potentially mediating actions of prolactin on hypothalamic function. To investigate whether GABA is involved in feedback regulation of TIDA neurons, we examined the physiological consequences of conditional deletion of Prlr in GABAergic neurons. For comparison, we also examined mice in which Prlr were deleted from most forebrain neurons. Both neuron-specific and GABA-specific recombination of the Prlr gene occurred throughout the hypothalamus and in some extrahypothalamic regions, consistent with the known distribution of Prlr expression, indicative of knock-out of Prlr. This was confirmed by a significant loss of prolactin-induced phosphorylation of STAT5, a marker of prolactin action. Several populations of GABAergic neurons that were not previously known to be prolactin-sensitive, notably in the medial amygdala, were identified. Approximately 50% of dopamine neurons within the arcuate nucleus were labeled with a GABA-specific reporter, but Prlr deletion from these dopamine/GABA neurons had no effect on feedback regulation of prolactin secretion. In contrast, Prlr deletion from all dopamine neurons resulted in profound hyperprolactinemia. The absence of coexpression of tyrosine hydroxylase, a marker for dopamine production, in GABAergic nerve terminals in the median eminence suggested that rather than a functional redundancy within the TIDA population, the dopamine/GABA neurons in the arcuate nucleus represent a subpopulation with a functional role distinct from the regulation of prolactin secretion., Significance Statement: Using a novel conditional deletion of the prolactin receptor, we have identified functional subpopulations in hypothalamic dopamine neurons. Although commonly considered a uniform population of neuroendocrine neurons involved in the control of prolactin secretion, we have shown that approximately half of these neurons express GABA as well as dopamine, but these neurons are not necessary for the feedback regulation of prolactin secretion. The absence of tyrosine hydroxylase in GABAergic nerve terminals in the median eminence suggests that only the non-GABAergic dopamine neurons are involved in the control of pituitary prolactin secretion, and the GABAergic subpopulation may function as interneurons within the arcuate nucleus to regulate other aspects of hypothalamic function., (Copyright © 2016 the authors 0270-6474/16/369173-13$15.00/0.)

Dietary omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), docosahexaenoic acid (DHA, C22:6) and eicosapentaenoic acid (EPA, C20:5) are usually derived from marine fish. Although production of both EPA and DHA has been engineered into land plants, including Arabidopsis, Camelina sativa and Brassica juncea, neither has been produced in commercially relevant amounts in a widely grown crop. We report expression of a microalgal polyketide synthase-like PUFA synthase system, comprising three multidomain polypeptides and an accessory enzyme, in canola (Brassica napus) seeds. This transgenic enzyme system is expressed in the cytoplasm, and synthesizes DHA and EPA de novo from malonyl-CoA without substantially altering plastidial fatty acid production. Furthermore, there is no significant impact of DHA and EPA production on seed yield in either the greenhouse or the field. Canola oil processed from field-grown grain contains 3.7% DHA and 0.7% EPA, and can provide more than 600 mg of omega-3 LC-PUFAs in a 14 g serving.

It has been suggested that lipoprotein abnormalities may contribute to the pulmonary arteriolar dysfunction observed in pulmonary arterial hypertension (PAH). High-density lipoprotein cholesterol (HDL) has vasodilatory, anti-inflammatory, and endothelial protective properties. We hypothesized that a higher serum HDL level may be advantageous for survival in PAH and that the serum HDL level at diagnosis would be an independent predictor of survival in PAH and be additive to previously validated predictors of survival. This study included all patients with PAH seen at the Mayo Clinic Pulmonary Hypertension Clinic from January 1, 1995, to December 31, 2009, who had a baseline HDL measurement. Mortality was analyzed over 5 years using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards ratios were calculated to evaluate the relation between baseline HDL level and survival. HDL levels were available for 227 patients. Higher HDL levels were associated with significantly lower mortality. Patients with an HDL >54 mg/dl at diagnosis had a 5-year survival of 59%. By comparison those with an HDL <34 mg/dl had a 5-year survival of 30%. On multivariate analysis, higher HDL was associated with an age-adjusted risk ratio for death of 0.78 (CI 0.67 to 0.91; p <0.01) per 10 mg/dl increase. In conclusion, HDL was an independent predictor of survival in PAH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To evaluate the inter-rater reliability of measuring structural changes in the tendon of patients, clinically diagnosed with supraspinatus tendinopathy (cases) and healthy participants (controls), on ultrasound (US) images captured by standardised procedures., Methods: A total of 40 participants (24 patients) were included for assessing inter-rater reliability of measurements of fibrillar disruption, neovascularity, as well as the number and total length of calcifications and tendon thickness. Linear weighted κ, intraclass correlation (ICC), SEM, limits of agreement (LOA) and minimal detectable change (MDC) were used to evaluate reliability., Results: 'Moderate-almost perfect' κ was found for grading fibrillar disruption, neovascularity and number of calcifications (k 0.60-0.96). For total length of calcifications and tendon thickness, ICC was 'excellent' (0.85-0.90), with SEM(Agreement) ranging from 0.63 to 2.94 mm and MDC(group) ranging from 0.28 to 1.29 mm. In general, SEM, LOA and MDC showed larger variation for calcifications than for tendon thickness., Conclusions: Inter-rater reliability was moderate to almost perfect when a standardised procedure was applied for measuring structural changes on captured US images and movie sequences of relevance for patients with supraspinatus tendinopathy. Future studies should test intra-rater and inter-rater reliability of the method in vivo for use in clinical practice, in addition to validation against a gold standard, such as MRI., Trial Registration Number: NCT01984203; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Immobilization causes rapid and massive bone loss. By comparing Botulinum Toxin A (BTX)-induced bone loss in mouse strains with different genetic backgrounds we investigated whether the genetic background had an influence on the severity of the osteopenia. Secondly, we investigated whether BTX had systemic effects on bone. Female mice from four inbred mouse strains (BALB/cJ, C57BL/6 J, DBA/2 J, and C3H/HeN) were injected unilaterally with BTX (n = 10/group) or unilaterally with saline (n = 10/group). Mice were euthanized after 21 days, and the bone properties evaluated using μCT, DXA, bone histomorphometry, and mechanical testing. BTX resulted in substantially lower trabecular bone volume fraction (BV/TV) and trabecular thickness in all mouse strains. The deterioration of BV/TV was significantly greater in C57BL/6 J (- 57%) and DBA/2 J (- 60%) than in BALB/cJ (- 45%) and C3H/HeN (- 34%) mice. The loss of femoral neck fracture strength was significantly greater in C57BL/6 J (- 47%) and DBA/2 J (- 45%) than in C3H (- 25%) mice and likewise the loss of mid-femoral fracture strength was greater in C57BL/6 J (- 17%), DBA/2 J (- 12%), and BALB/cJ (- 9%) than in C3H/HeN (- 1%) mice, which were unaffected. Using high resolution μCT we found no evidence of a systemic effect on any of the microstructural parameters of the contralateral limb. Likewise, there was no evidence of a systemic effect on the bone strength in any mouse strain. We did, however, find a small systemic effect on aBMD in DBA/2 J and C3H/HeN mice. The present study shows that BTX-induced immobilization causes the greatest loss of cortical and trabecular bone in C57BL/6 J and DBA/2 J mice. A smaller loss of bone microstructure and fracture strength was seen in BALB/cJ mice, while the bone microstructure and fracture strength of C3H/HeN mice were markedly less affected. This indicates that BTX-induced loss of bone is mouse strain dependent. We found only minimal systemic effects of BTX.

The aims were to compile a schematic overview of clinical scapular assessment methods and critically appraise the methodological quality of the involved studies. A systematic, computer-assisted literature search using Medline, CINAHL, SportDiscus and EMBASE was performed from inception to October 2013. Reference lists in articles were also screened for publications. From 50 articles, 54 method names were identified and categorized into three groups: (1) Static positioning assessment (n = 19); (2) Semi-dynamic (n = 13); and (3) Dynamic functional assessment (n = 22). Fifteen studies were excluded for evaluation due to no/few clinimetric results, leaving 35 studies for evaluation. Graded according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN checklist), the methodological quality in the reliability and validity domains was "fair" (57%) to "poor" (43%), with only one study rated as "good". The reliability domain was most often investigated. Few of the assessment methods in the included studies that had "fair" or "good" measurement property ratings demonstrated acceptable results for both reliability and validity. We found a substantially larger number of clinical scapular assessment methods than previously reported. Using the COSMIN checklist the methodological quality of the included measurement properties in the reliability and validity domains were in general "fair" to "poor". None were examined for all three domains: (1) reliability; (2) validity; and (3) responsiveness. Observational evaluation systems and assessment of scapular upward rotation seem suitably evidence-based for clinical use. Future studies should test and improve the clinimetric properties, and especially diagnostic accuracy and responsiveness, to increase utility for clinical practice.

Objectives: To survey internal medicine physicians and residents who have completed residency in three different eras of medical training regarding their experiences during their intern year and their perceptions of duty-hour reform., Methods: An online survey was administered to 268 residents, fellows, and staff physicians who had completed or were completing residency during one of three eras of training: before the 80-hour work week, after the 80-hour work week (instituted in 2003), and after the 16-hour limit on continuous shifts for interns (instituted in 2011). The survey assessed experiences during their intern year of residency and perceptions regarding resident duty-hour reform., Results: The majority of respondents (n = 32; 54%) indicated that duty-hour restrictions would result in residents being less prepared for their future careers. In addition, 36% (n = 21) of respondents anticipated a decrease in the quality of patient care under the restricted duty hours. A total of 41% (n = 24) were undecided regarding the impact of duty-hour reform on patient care. Respondents reported time spent on independent study, research, and conference attendance did not increase following the institution of duty-hour restrictions., Conclusions: Survey responses indicated that after 18 months of experience with the Accreditation Council for Graduate Medical Education duty-hour restrictions, physician opinions were mixed and a substantial number remain undecided regarding the impact of duty-hour restrictions on resident career preparedness and the quality of patient care.

Neuromuscular control of the scapular muscles is important in the etiology of shoulder pain. Electromyographical (EMG) biofeedback in healthy people has been shown to support a selective activation of the lower compartment of the trapezius muscle, specifically. The aim of the present paper was to investigate whether patients with Subacromial Impingement Syndrome (SIS) were able to selectively activate the individual compartments within the trapezius muscle, with and without EMG biofeedback to the same extent as healthy controls (No-SIS). Fifteen SIS and 15 No-SIS participated in the study. Sessions with and without visual biofeedback were conducted. Surface EMG was recorded from four compartments of the trapezius muscle. Selective activation was defined as activation above 12% with other muscle parts below 1.5% or activation ratio at or above 95% of the total activation. Without biofeedback significantly fewer SIS subjects than No-SIS achieved selective activation (p=0.02-0.03). The findings of the study show that without biofeedback No-SIS had a superior scapular muscle control. However, when provided with visual EMG feedback the SIS group performed equally well as the No-SIS group. This indicated that individuals with SIS may benefit from biofeedback training to gain control of the neuromuscular function of the scapular muscle., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Imbalance of neuromuscular activity in the scapula stabilizers in subjects with Subacromial Impingement Syndrome (SIS) is described in restricted tasks and specific populations. Our aim was to compare the scapular muscle activity during a voluntary movement task in a general population with and without SIS (n=16, No-SIS=15). Surface electromyography was measured from Serratus anterior (SA) and Trapezius during bilateral arm elevation (no-load, 1kg, 3kg). Mean relative muscle activity was calculated for SA and the upper (UT) and lower part of trapezius (LWT), in addition to activation ratio and time to activity onset. In spite of a tendency to higher activity among SIS 0.10-0.30 between-group differences were not significant neither in ratio of muscle activation 0.80-0.98 nor time to activity onset 0.53-0.98. The hypothesized between-group differences in neuromuscular activity of Trapezius and Serratus was not confirmed. The tendency to a higher relative muscle activity in SIS could be due to a pain-related increase in co-activation or a decrease in maximal activation. The negative findings may display the variation in the specific muscle activation patterns depending on the criteria used to define the population of impingement patients, as well as the methodological procedure being used, and the shoulder movement investigated., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Elevated prolactin during pregnancy increases neurogenesis in the subventricular zone of the lateral ventricle (SVZ) of the maternal brain. Evidence from our laboratory has shown that low prolactin in early pregnancy, and the consequent suppression of neurogenesis in the SVZ in the adult brain, is associated with increased postpartum anxiety and markedly impaired maternal behavior. Daughters of low prolactin mothers also display increased anxiety and a significant delay in the onset of puberty, which is associated with epigenetic changes in neuronal development (see Fig. 1). This suggests that, in rodents, low prolactin in early pregnancy exerts long-term effects that influence maternal mood postpartum, and offspring development. This mini-review aims to summarize the evidence showing that the prolactin-induced increase in SVZ neurogenesis during pregnancy underlies normal postpartum maternal interactions with pups., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Evolutionary adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung is limited by genetic variation, which depends on rates of horizontal gene transfer and mutation supply. Because each may increase following secondary infection or mutator emergence, we sought to ascertain the incidence of secondary infection and genetic variability in populations containing or lacking mutators. Forty-nine strains collected over 3 years from 16 patients were phenotyped for antibiotic resistance and mutator status and were genotyped by repetitive-sequence PCR (rep-PCR), pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). Though phenotypic and genetic polymorphisms were widespread and clustered more strongly within than between longitudinal series, their distribution revealed instances of secondary infection. Sequence data, however, indicated that interlineage recombination predated initial strain isolation. Mutator series were more likely to be multiply antibiotic resistant, but not necessarily more variable in their nucleotide sequences, than nonmutators. One mutator and one nonmutator series were sequenced at mismatch repair loci and analyzed for gene content using DNA microarrays. Both were wild type with respect to mutL, but mutators carried an 8-bp mutS deletion causing a frameshift mutation. Both series lacked 126 genes encoding pilins, siderophores, and virulence factors whose inactivation has been linked to adaptation during chronic infection. Mutators exhibited loss of severalfold more genes having functions related to mobile elements, motility, and attachment. A 105-kb, 86-gene deletion was observed in one nonmutator that resulted in loss of virulence factors related to pyoverdine synthesis and elements of the multidrug efflux regulon. Diminished DNA repair activity may facilitate but not be absolutely required for rapid evolutionary change.

Introduction A specific algorithm has been proposed for classifying impingement related shoulder pain in athletes with overhead activity. Data on the inter-examiner reproducibility of the suggested clinical tests and criteria and their mutual dependencies for identifying subacromial impingement symptoms (SIS) are not available. Objective To test the inter-examiner reproducibility of selected tests and criteria suggested for classifying SIS and the mutual dependencies of each of the individual tests and SIS. Method A standardised three-phase protocol for clinical reproducibility studies was followed, consisting of a training, an overall agreement and a study phase. To proceed to the study phase, an overall agreement of 0.80 was required. In total 10, 20 and 44 subjects were included in the three phases, respectively. The case prevalence in the study phase was 50%. The inclusion criterion for cases was ≥3, and for controls ≤1 positive test out of four. Cohen's κ statistics were used for calculating agreement. Results In the overall agreement phase, an agreement of 0.90 was obtained, while in the study phase it was 0.98 with a κ of 0.95 for SIS. κ Values for the individual tests varied between 0.60 and 0.95. Mutual dependencies between each test and SIS showed Neer's test with anterior pain to be most often used to determine SIS. Conclusions Inter-examiner reproducibility was moderate to almost perfect for the selected tests and criteria for SIS. The next challenge will be to establish reproducibility in clinical practice, as well as the validity of the tests and criteria for SIS.

High prolactin during pregnancy, which is essential for normal postpartum maternal behavior, increases neurogenesis in the subventricular zone of the lateral ventricle (SVZ) of the maternal brain. Because SVZ mitogenesis generates new olfactory neurons and may contribute to perception of novel odorants, we hypothesized that the prolactin-induced increase in SVZ mitogenesis during pregnancy might be important for normal maternal interactions with pups. To investigate this hypothesis, prolactin secretion was suppressed for 3 d early in pregnancy in mice, using a carefully timed dose of bromocriptine. The bromocriptine-induced reduction in prolactin prevented the normal increase in generation of neural progenitors in the SVZ of the maternal brain. Another group of bromocriptine-treated animals were allowed to continue their pregnancy until term, and then maternal behaviors were evaluated postpartum. Low prolactin during early pregnancy, and the consequent suppression of mitogenesis in the SVZ of the maternal brain, was subsequently followed by increased postpartum anxiety and markedly impaired maternal behavior. In another group of pregnant females, injections of the mitotic inhibitor methylazoxymethanol to specifically suppress neurogenesis in the mother during early pregnancy without affecting prolactin secretion also caused postpartum anxiety and impaired maternal behavior. These data demonstrate that prolactin-induced increase in generation of neural progenitors in the SVZ of the maternal brain during early pregnancy is required for normal expression of postpartum maternal behaviors.