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At the 2020 American String Teachers Association (ASTA) Conference held in Orlando Florida, an attendee of the Wellness Committee Listening Session recommended that a study be conducted to determine the prevalence and awareness of mental health concerns among students and teachers within the organization. Members agreed that there is more needed to be understood so that ASTA could provide professional development webinars, resources, as well as local, state, and national conference sessions. In response to this request and the clear need for more information, a survey was developed and deployed to the ASTA membership in the fall of 2020. Follow-up interviews with members who volunteered in response to an invitation on the survey were conducted in the spring and early summer of 2021. Teachers reported a high prevalence of student mental health issues prior to and during the pandemic and reported concerning levels of work overload, compassion fatigue/burnout, and mental health issues. Generational differences in mental health perceptions were noted, as were opportunities to provide targeted professional development and community-level services.

Purpose: The purpose of this study was to explore potential differences in suprathreshold auditory function among native and nonnative speakers of English as a function of age. Method: Retrospective analyses were performed on three large data sets containing suprathreshold auditory tests completed by 5,572 participants who were self-identified native and nonnative speakers of English between the ages of 18-65 years, including a binaural tone detection test, a digit identification test, and a sentence recognition test. Results: The analyses show a significant interaction between increasing age and participant group on tests involving speech-based stimuli (digit strings, sentences) but not on the binaural tone detection test. For both speech tests, differences in speech recognition emerged between groups during early adulthood, and increasing age had a more negative impact on word recognition for nonnative compared to native participants. Age-related declines in performance were 2.9 times faster for digit strings and 3.3 times faster for sentences for nonnative participants compared to native participants. Conclusions: This set of analyses extends the existing literature by examining interactions between aging and self-identified native English speaker status in several auditory domains in a cohort of adults spanning young adulthood through middle age. The finding that older nonnative English speakers in this age cohort may have greater-than-expected deficits on speech-in-noise perception may have clinical implications on how these individuals should be diagnosed and treated for hearing difficulties.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

Two-stage testing is a form of collaborative assessment that creates an active learning environment during test taking. In two-stage testing, students first complete an exam individually, and then complete a subset of the same questions as part of a learning team with the ultimate exam score being a weighted average of the individual and team portions. In the second (team-based) part of the exam, students are encouraged to discuss solutions until a consensus among team members is achieved, thus actively engaging students with course material and each other during the exam. A short open-ended survey was administered to students at the end of the semester, and the responses coded by thematic analysis, with themes generated using inductive coding based on the principles of grounded theory. The most important conclusion was that students overwhelmingly preferred two-stage tests for the development of positive peer relationships in class. The most common themes that emerged from student responses involved positive feelings from forced interaction with their peers, the benefits of meeting and socializing with other students, sharing of knowledge with others, and solidarity or positive affect towards the process of working as part of a team. Finally, students also expressed an overall preference for two-stage exams when compared to solely individual, one-stage exams.

Abstract Background Mitochondria represent key organelles influencing cellular homeostasis and have been implicated in the signalling events regulating protein synthesis. Methods We examined whether mitochondrial bioenergetics (oxidative phosphorylation and reactive oxygen species (H2O2) emission, ROS) measured in vitro in permeabilized muscle fibres represent regulatory factors for integrated daily muscle protein synthesis rates and skeletal muscle mass changes across the spectrum of physical activity, including free‐living and bed‐rest conditions: n = 19 healthy, young men (26 ± 4 years, 23.4 ± 3.3 kg/m2) and following 12 weeks of resistance‐type exercise training: n = 10 healthy older men (70 ± 3 years, 25.2 ± 2.1 kg/m2). Additionally, we evaluated the direct relationship between attenuated mitochondrial ROS emission and integrated daily myofibrillar and sarcoplasmic protein synthesis rates in genetically modified mice (mitochondrial‐targeted catalase, MCAT). Results Neither oxidative phosphorylation nor H2O2 emission were associated with muscle protein synthesis rates in healthy young men under free‐living conditions or following 1 week of bed rest (both P > 0.05). Greater increases in GSSG concentration were associated with greater skeletal muscle mass loss following bed rest (r = −0.49, P 0.05). Additionally, MCAT mice displayed no differences in myofibrillar (2.62 ± 0.22 vs. 2.75 ± 0.15%/day) and sarcoplasmic (3.68 ± 0.35 vs. 3.54 ± 0.35%/day) protein synthesis rates when compared with wild‐type mice (both P > 0.05). Conclusions Mitochondrial oxidative phosphorylation and reactive oxygen emission do not seem to represent key factors regulating muscle protein synthesis or muscle mass regulation across the spectrum of physical activity.

The present study investigated the effect of supplementing a multi-carbohydrase enzyme complex (MCE) in corn–soy-based diets of Pekin ducks. The treatments were as follows: positive control (PC, 2980 and 3120 kcal/kg for starter and grower, respectively); negative control (NC, −132 kcal/kg energy reduction to PC achieved by reduction of fat and wheat middlings as filler); NC + MCE at 75 ppm (E75); 100 ppm (E100); and 125 ppm (E125) randomly distributed in 10 replicate pens with 25 birds each. Performance was evaluated after 14 and 35 d. On day 36 of the trial, five ducks/pen were processed to evaluate carcass traits. During days 1–14, the PC had a lower (p < 0.01) feed intake compared to all other treatments. At 14 and 35 d of age the NC decreased (p < 0.001) the body weight (BW) of the ducks compared to the PC by −8.3% and −5.3%, respectively. The NC BW was lower (p < 0.001) compared to all MCE-supplemented treatments at 14 and 35 d. The BW of E75, E100, and E125 treatments was not different (p > 0.05) from the PC at both evaluation periods. Cumulatively (1–35 d), the NC resulted in a weight-adjusted FCR increase (p = 0.001) of 9.9% compared to the PC, and the FCR of E75, E100, and E125 were able to recover 72.3%, 66.4%, and 63.5%, respectively, compared to the PC. The carcass and breast weights were lower (p < 0.001) in the NC compared to all other treatments, and no differences (p > 0.05) were observed between the MCE-supplemented treatments and the PC. In conclusion, these results suggest that the MCE supplementation can maintain duck growth performance with no negative effects on carcass traits in energy-reduced corn–soybean meal-based diets. From the results of the trial, 75 ppm MCE delivered the best performance recovery and 125 ppm MCE supplementation had the best % breast yield.

Abstract Inspired by the starfish's unique ability to achieve flexibility and posture-holding with minimal energy expenditure, we present a novel bioinspired morphing structure. Our two-component design, consisting of a thermoplastic mesh and elastomeric jacket, effectively mimics the functions of the starfish's ossicles, mutable collagenous tissues, and derma. This structure exhibits a remarkable combination of self-healing, time-dependent shape memory, and self-posture-holding properties. Systematic variations in mesh geometry demonstrate precise control over structural stiffness and thermal response, enabling customization for specific applications. The structure's scalability and ease of fabrication further enhance its adaptability. We experimentally demonstrate the potential of our biomimetic morphing structure using several prototypes. This work lays the foundation for developing a new type of versatile morphing structures with applications in diverse fields, including robotics, biomedical devices, and adaptive structures.

Abstract Background Children with congenital heart disease (CHD) who undergo open-heart surgery are at risk of developmental impairment, including motor delay, which contributes to parental concerns. Additionally, parents experience prolonged stress associated with their child’s disease. There is a lack of early motor interventions in infants with CHD accounting for parental burdens. We developed a family-tailored early motor intervention (EMI-Heart), aiming to promote motor development in infants with CHD and family well-being. The primary aim was to evaluate the feasibility of the study design and the intervention. The secondary aim was to evaluate differences between the intervention and the control group in motor outcomes and family well-being at baseline (3–5 months), post-treatment (6–8 months), and at follow-up (12 months). Method In this single-centre feasibility randomized control trial (RCT), infants with CHD after open-heart surgery without genetic or major neurological comorbidities were randomly allocated to EMI-Heart or the control group (standard of care). EMI-Heart’s key elements promote postural functional activities and encourage parental sensitivity to infants’ motor and behaviour cues. Infants assigned to EMI-Heart received nine sessions of early motor intervention at home, in the hospital, and online for a duration of 3 months by a paediatric physiotherapist. We performed descriptive statistics for feasibility and secondary outcomes. Results The recruitment rate was 59% (10/17), all participating families completed the study (10/10), and the intervention duration was 3.9 months (± 0.54), including nine intervention sessions per family. Median acceptability to parents was 3.9 (1 = not agree–4 = totally agree, Likert scale). The paediatric physiotherapist considered the intervention as feasible. The comparison of motor outcomes did not show differences between groups. However, we detected improved reliable change scores in family well-being outcomes for families of the intervention group compared to the controls. Conclusions Our research indicates that EMI-Heart is a feasible intervention for infants with CHD after open-heart surgery. The intervention was highly acceptable both to parents and to the paediatric physiotherapist. Online treatment sessions offer a valuable alternative to home and hospital visits. This feasibility RCT provides a foundation for a future full trial. Trial registration ClinicalTrials.gov, NCTT04666857. Registered 23.11.2020.

Research indicates that establishing a strong foundation in early mathematics is essential for later academic learning. Previous research with students who are deaf or hard of hearing (DHH) has shown varying differences in the performance and achievement when compared to typically hearing (TH) students. While the majority of research in this area has been conducted in the United States, studies in other countries suggest that these differences may be global. The present study investigated the early mathematics abilities of 3-year-old DHH children enrolled in family-centred early intervention in the Netherlands. Fifty-three DHH and TH children were given an adapted version of the Early Mathematics Performance Diagnostic. Results showed that on average, the DHH and the TH children performed similarly on all domains, except for Measurement. Likewise, both groups showed similar mathematical knowledge in most early mathematics tasks measuring sub-concepts such as counting objects, shape matching, or measuring weight. Differences were identified in some basic tasks measuring the sub-concepts (e.g. rote counting, measuring time, solving puzzles), however, not on the more advanced tasks measuring these same sub-concepts. These findings are important for parents, teachers, and early interventionists.

Abstract Background Equine parvovirus hepatitis (EqPV‐H) can cause Theiler's disease and subclinical hepatitis in horses. Objectives Assess the frequency of subclinical EqPV‐H infection in hospitalized horses and to study viral transmission by investigating potential shedding routes. Animals One hundred sixteen equids, that presented to the University Equine Hospital of the University of Veterinary Medicine Vienna between February 2021 and March 2022, for causes other than hepatopathy. Methods In this cross‐sectional study, samples (serum, feces, nasal, and buccal swabs) of hospitalized horses were collected. Sera were screened for the presence of anti‐EqPV‐H antibodies by a luciferase immunoprecipitation system assay. Quantitative PCR was used for the detection of EqPV‐H DNA in the samples and a nested PCR was used for further validation. Results Seroprevalence was 10.3% (12/116) and viremia occurred in 12.9% (15/116) of the serologically positive horses. The detected viral load in serum varied from non‐quantifiable amount to 1.3 × 106 genome equivalents per milliliter of serum. A low viral load of EqPV‐H DNA was detected in 2 nasal swabs and 1 fecal sample. Conclusion and Clinical Importance EqPV‐H DNA was detected in nasal secretions and feces of viremic horses, which could pose a risk to naive hospitalized horses. It is advisable to screen hospitalized horses that are potential donors of blood or plasma to reduce the risk of iatrogenic EqPV‐H transmission.

Abstract Background Research on prostate cancer is mostly performed using cell lines derived from metastatic disease, not reflecting stages of tumor initiation or early progression. Establishment of cancer cell lines derived from the primary tumor site has not been described so far. By definition, cancer cells are able to be cultured indefinitely, whereas normal epithelial cells undergo senescence in vitro. Epithelial cells can be immortalized, accomplished by using viral integration of immortalization factors. Viral approaches, however, might be impaired by regulatory and safety issues as well as random integration into regulatory genetic elements, modifying precise gene expression. We intend to use surgical specimen of prostate cancer patients to (i) prove for establishment of cancer cell lines, and (ii) perform non-viral, Sleeping Beauty (SB) transposase-based immortalization of prostate epithelial cells. Methods Radical prostatectomy samples of prostate cancer patients (n = 4) were dissociated and cultured in vitro. Cells were cultivated either without or after non-viral, Sleeping-Beauty transposase-based stable transfection with immortalization factors SV40LT and hTERT. Established cell lines were analyzed in vitro and in vivo for characteristics of prostate (cancer) cells. Results Initial cell cultures without genetic manipulation underwent senescence within ≤ 15 passages, demonstrating inability to successfully derive primary prostate cancer cell lines. By using SB transposase-based integration of immortalization factors, we were able to establish primary prostate cell lines. Three out of four cell lines displayed epithelial characteristics, however without expression of prostate (cancer) characteristics, e.g., androgen receptor. In vivo, one cell line exhibited tumorigenic potential, yet characteristics of prostate adenocarcinoma were absent. Conclusion Whereas no primary prostate cancer cell line could be established, we provide for the first-time immortalization of primary prostate cells using the SB transposase system, thereby preventing regulatory and molecular issues based on viral immortalization approaches. Although, none of the newly derived cell lines demonstrated prostate cancer characteristics, tumor formation was observed in one cell line. Given the non-prostate adenocarcinoma properties of the tumor, cells have presumably undergone oncogenic transformation rather than prostate cancer differentiation. Still, these cell lines might be used as a tool for research on prostate cancer initiation and early cancer progression.

IntroductionOpioid drugs are potent analgesics that mimic the endogenous opioid peptides, endorphins and enkephalins, by activating the µ-opioid receptor. Opioid use is limited by side effects, including significant risk of opioid use disorder. Improvement of the effect/side effect profile of opioid medications is a key pursuit of opioid research, yet there is no consensus on how to achieve this goal. One hypothesis is that the degree of arrestin-3 recruitment to the µ-opioid receptor impacts therapeutic utility. However, it is not clear whether increased or decreased interaction of the µ-opioid receptor with arrestin-3 would reduce compulsive drug-seeking.MethodsWe utilized three genotypes of mice with varying abilities to recruit arrestin-3 to the µ-opioid receptor in response to morphine in a novel longitudinal operant self-administration model. We also created a quantitative method to define compulsivity in drug-seeking based on a multi-variate analysis of several operant response variables.ResultsWe demonstrate that arrestin-3 knockout and wild type mice have highly variable drug-seeking behavior with few genotype differences. In contrast, in mice where the µ-opioid receptor strongly recruits arrestin-3, drug-seeking behavior is much less varied. We found that mice lacking arrestin-3 were more likely to meet the criteria for compulsivity whereas mice with enhanced arrestin-3 recruitment did not develop a compulsive phenotype.ConclusionThese experiments show that a lack of arrestin-3 is not protective against the abuse liability of morphine in an operant self-administration context. Our data also suggest that opioids that engage both G protein and arrestin-3, recapitulating the endogenous signaling pattern, will reduce abuse liability.

Background and study aimRegular physical activity is highly recommended for patients with Fontan hemodynamics. Our aim was to investigate the effects of a long-term individualized home-based endurance training (IHET) on a bicycle ergometer in combination with inspiratory muscle training (IMT) in pediatric and adult patients after Fontan palliation. Additionally, factors influencing the trainability of Fontan palliated patients were analyzed.MethodsFrom 2018 to 2021 a single-center prospective study was performed initially including 25 Fontan palliated patients. During study period nine patients were excluded due to incompliance. A Magbike® bicycle ergometer (DKN Technology, France) was used for IHET and a POWERbreathe® Medic plus device (HaB GmbH, Germany) was utilized for the IMT. Over the study period, bike training was increased from 90 min of basic endurance training per week to additional 25 min of interval training per week. IMT consisted of 30 breaths per day for 6–7 days per week with pressure adaption over time. Patients underwent cardiopulmonary exercise testing (CPET) and body plethysmography including measurement of respiratory muscle strength at baseline and at follow-up examinations at 4, 10 and 22 months.ResultsFollow-up examinations were completed by 18/25 patients (72.0%) at 4 and 10 months and 16/25 patients (64.0%) at 22 months. Median exercise capacity slightly increased by 0.13 W/kg from baseline to last follow-up (p = 0.055, 95%CI: 0.0–0.36). However, a significant increase of oxygen pulse of 0.7 ml/beat (p = 0.006, 95%CI: 0.38–2.22) was detectable. IMT significantly improved respiratory function with an increase of inspiratory vital capacity (VCin/reference) by 4.0% (p = 0.016, 95%CI: 0.8–8). Median maximal inspiratory pressure increased by 1.2 kPa (p = 0.003, 95%CI: 0.64–3.19) and expiratory pressure by 1.5 kPa (p = 0.036, 95%CI: 0.08–2.29). No adverse events or unplanned interventions occurred during the study. Patients' subjective quality of life did not significantly change over the study period.ConclusionIn Fontan palliated patients, IHET in combination with IMT leads to a significant increase in oxygen pulse, inspiratory vital capacity as well as median maximal inspiratory and expiratory pressure but not to significant improvement of quality of life. Fontan patients should be encouraged to perform regular home-based exercise training.

IntroductionRespiratory viral infections (RVIs) are a major global contributor to morbidity and mortality. The susceptibility and outcome of RVIs are strongly age-dependent and show considerable inter-population differences, pointing to genetically and/or environmentally driven developmental variability. The factors determining the age-dependency and shaping the age-related changes of human anti-RVI immunity after birth are still elusive. MethodsWe are conducting a prospective birth cohort study aiming at identifying endogenous and environmental factors associated with the susceptibility to RVIs and their impact on cellular and humoral immune responses against the influenza A virus (IAV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MIAI birth cohort enrolls healthy, full-term neonates born at the University Hospital Würzburg, Germany, with follow-up at four defined time-points during the first year of life. At each study visit, clinical metadata including diet, lifestyle, sociodemographic information, and physical examinations, are collected along with extensive biomaterial sampling. Biomaterials are used to generate comprehensive, integrated multi-omics datasets including transcriptomic, epigenomic, proteomic, metabolomic and microbiomic methods. DiscussionThe results are expected to capture a holistic picture of the variability of immune trajectories with a focus on cellular and humoral key players involved in the defense of RVIs and the impact of host and environmental factors thereon. Thereby, MIAI aims at providing insights that allow unraveling molecular mechanisms that can be targeted to promote the development of competent anti-RVI immunity in early life and prevent severe RVIs.Clinical trial registrationhttps://drks.de/search/de/trial/, identifier DRKS00034278.

Summary: Cancer stem cells (CSCs) established from surgical biopsies closely mimic the human context and can be used to investigate disease mechanisms, genetic fitness, and therapeutic evaluation. Here, we present a protocol for the derivation of primary patient-derived CSC lines from ependymal tumors. We describe the necessary steps, from surgical intervention and biopsy to the dissociation of ependymomas to derive cultures. We then detail procedures for cell line propagation and define the characteristics of these primary cancer cell lines.For complete details on the use and execution of this protocol, please refer to Michealraj et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

SUMMARY: The objective of this study was to evaluate the effect of a commercially available Bacillus-based direct fed microbial (DFM, Amnil®, United Animal Health, Sheridan, IN) on Pekin duck performance and welfare. The study consisted of 5 dietary treatments, each consisting of 10 replicate pens and 25 straight-run day-of-hatch ducks/pen. The treatments included a commercial-type basal diet (CON), or the basal diet supplemented with 125 ppm (A-125), or 250 ppm (A-250), or 500 ppm (A-500), or 750 ppm (A-750) DFM. On D 14 and 35 performance was evaluated. Gait scores (GS), footpad lesions (FPL), complete cell blood counts, nitrogen digestibility, and total plasma corticosterone levels (CORT) were measured at D 35. The average daily feed intake (ADFI) and feed conversion ratio (FCR) overall were higher in the CON than all other treatments. Body weights did not differ between treatments. The H/L Ratio and total plasma corticosterone levels for CON were higher than all of treatments. Nitrogen digestibility for CON was lower than all other treatments. Gait Scores and Footpad Lesion Scores did not differ between treatments. Utilization of the DFM at any inclusion rate improved feed efficiency, reduced stress susceptibility, and improved nitrogen digestibility. While gait scores, footpad scores, and body weights were not affected by supplementation, feeding this DFM to Pekin ducks can improve their performance and welfare.

Abstract In the last few decades, developers of new drugs, biologics, and devices have increasingly leveraged digital health technologies (DHTs) to assess clinical trial digital endpoints. To our knowledge, a comprehensive assessment of the financial net benefits of digital endpoints in clinical trials has not been conducted. We obtained data from the Digital Medicine Society (DiMe) Library of Digital Endpoints and the US clinical trials registry, ClinicalTrials.gov. The benefit metrics are changes in trial phase duration and enrollment associated with the use of digital endpoints. The cost metric was obtained from an industry survey of the costs of including digital endpoints in clinical trials. We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess financial value. The value measure is the increment in eNPV that occurs when digital endpoints are employed. We also calculated a return on investment (ROI) as the ratio of the estimated increment in eNPV to the mean digital endpoint implementation cost. For phase II trials, the increase in eNPV varied from $2.2 million to $3.3 million, with ROIs between 32% and 48% per indication. The net benefits were substantially higher for phase III trials, with the increase in eNPV varying from $27 million to $40 million, with ROIs that were four to six times the investment. The use of digital endpoints in clinical trials can provide substantial extra value to sponsors developing new drugs, with high ROIs.