Changing the Paradigm for School Hearing Screening Globally: Evaluation of Screening Protocols From Two Randomized Trials in Rural Alaska.

OBJECTIVES: Diagnostic accuracy was evaluated for various screening tools, including mobile health (mHealth) pure-tone screening, tympanometry, distortion product otoacoustic emissions (DPOAE), and inclusion of high frequencies to determine the most accurate screening protocol for identifying children with hearing loss in rural Alaska where the prevalence of middle ear disease is high. DESIGN: Hearing screening data were collected as part of two cluster randomized trials conducted in 15 communities in rural northwest Alaska. All children enrolled in school from preschool to 12th grade were eligible. Analysis was limited to data collected 2018 to 2019 (n = 1449), when both trials were running and measurement of high frequencies were included in the protocols. Analyses included estimates of diagnostic accuracy for each screening tool, as well as exploring performance by age and grade. Multiple imputation was used to assess diagnostic accuracy in younger children, where missing data were more prevalent due to requirements for conditioned responses. The audiometric reference standard included otoscopy, tympanometry, and high frequencies to ensure detection of infection-related and noise-induced hearing loss. RESULTS: Both the mHealth pure-tone screen and DPOAE screen performed better when tympanometry was added to the protocol (increase in sensitivity of 19.9%, 95% Confidence Interval (CI): 15.9 to 24.1 for mHealth screen, 17.9%, 95% CI: 14.0 to 21.8 for high-frequency mHealth screen, and 10.4%, 95% CI: 7.5 to 13.9 for DPOAE). The addition of 6 kHz to the mHealth pure-tone screen provided an 8.7 percentage point improvement in sensitivity (95% CI: 6.5 to 11.3). Completeness of data for both the reference standard and the mHealth screening tool differed substantially by age, due to difficulty with behavioral testing in young children. By age 7, children were able to complete behavioral testing, and data indicated that high-frequency mHealth pure-tone screen with tympanometry was the superior tool for children 7 years and older. For children 3 to 6 years of age, DPOAE plus tympanometry performed the best, both for complete data and multiply imputed data, which better approximates accuracy for children with missing data. CONCLUSIONS: This study directly evaluated pure-tone, DPOAE, and tympanometry tools as part of school hearing screening in rural Alaskan children (3 to 18+ years). Results from this study indicate that tympanometry is a key component in the hearing screening protocol, particularly in environments with higher prevalence of infection-related hearing loss. DPOAE is the preferred hearing screening tool when evaluating children younger than 7 years of age (below 2nd grade in the United States) due to the frequency of missing data with behavioral testing in this age group. For children 7 years and older, the addition of high frequencies to pure-tone screening increased the accuracy of screening, likely due to improved identification of hearing loss from noise exposure. The lack of a consistent reference standard in the literature makes comparing across studies challenging. In our study with a reference standard inclusive of otoscopy, tympanometry, and high frequencies, less than ideal sensitivities were found even for the most sensitive screening protocols, suggesting more investigation is necessary to ensure screening programs are appropriately identifying noise- and infection-related hearing loss in rural, low-resource settings.

Prevalence of Childhood Hearing Loss in Rural Alaska.

OBJECTIVES: Childhood hearing loss has well-known lifelong consequences. Certain rural populations are at higher risk for infection-related hearing loss. For Alaska Native children, historical data on hearing loss prevalence suggest a higher burden of infection-related hearing loss, but updated prevalence data are urgently needed in this high-risk population. DESIGN: Hearing data were collected as part of two school-based cluster-randomized trials in 15 communities in rural northwest Alaska over two academic years (2017-2019). All enrolled children from preschool to 12th grade were eligible. Pure-tone thresholds were obtained using standard audiometry and conditioned play when indicated. The analysis included the first available audiometric assessment for each child (n = 1634 participants, 3 to 21 years), except for the high-frequency analysis, which was limited to year 2 when higher frequencies were collected. Multiple imputation was used to quantify the prevalence of hearing loss in younger children, where missing data were more frequent due to the need for behavioral responses. Hearing loss in either ear was evaluated using both the former World Health Organization (WHO) definition (pure-tone average [PTA] > 25 dB) and the new WHO definition (PTA ≥ 20 dB), which was published after the study. Analyses with the new definition were limited to children 7 years and older due to incomplete data obtained on younger children at lower thresholds. RESULTS: The overall prevalence of hearing loss (PTA > 25 dB; 0.5, 1, 2, 4 kHz) was 10.5% (95% confidence interval [CI], 8.9 to 12.1). Hearing loss was predominately mild (PTA >25 to 40 dB; 8.9%, 95% CI, 7.4 to 10.5). The prevalence of unilateral hearing loss was 7.7% (95% CI, 6.3 to 9.0). Conductive hearing loss (air-bone gap of ≥ 10 dB) was the most common hearing loss type (9.1%, 95% CI, 7.6 to 10.7). Stratified by age, hearing loss (PTA >25 dB) was more common in children 3 to 6 years (14.9%, 95% CI, 11.4 to 18.5) compared to children 7 years and older (8.7%, 95% CI, 7.1 to 10.4). In children 7 years and older, the new WHO definition increased the prevalence of hearing loss to 23.4% (95% CI, 21.0 to 25.8) compared to the former definition (8.7%, 95% CI, 7.1 to 10.4). Middle ear disease prevalence was 17.6% (95% CI, 15.7 to 19.4) and was higher in younger children (23.6%, 95% CI, 19.7 to 27.6) compared to older children (15.2%, 95% CI, 13.2 to 17.3). High-frequency hearing loss (4, 6, 8kHz) was present in 20.5% (95% CI, 18.4 to 22.7 [PTA >25 dB]) of all children and 22.8% (95% CI, 20.3 to 25.3 [PTA >25 dB]) and 29.7% (95% CI, 27.0 to 32.4 [PTA ≥ 20 dB]) of children 7 years and older (limited to year 2). CONCLUSIONS: This analysis represents the first prevalence study on childhood hearing loss in Alaska in over 60 years and is the largest cohort with hearing data ever collected in rural Alaska. Our results highlight that hearing loss continues to be common in rural Alaska Native children, with middle ear disease more prevalent in younger children and high-frequency hearing loss more prevalent with increasing age. Prevention efforts may benefit from managing hearing loss type by age. Lastly, continued research is needed on the impact of the new WHO definition of hearing loss on field studies.

Circulating tumor DNA monitoring for early recurrence detection in epithelial ovarian cancer.

OBJECTIVE: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. We examined the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for EOC by assessing its relationship with patient outcome and CA-125, pre-surgically and during post-treatment surveillance. METHODS: Plasma samples were collected from patients with stage I-IV EOC. Cohort A included patients with pre-surgical samples (N = 44, median follow-up: 2.7 years), cohort B and C included: patients with serially collected post-surgically (N = 12) and, during surveillance (N = 13), respectively (median follow-up: 2 years). Plasma samples were analyzed using a tumor-informed, personalized multiplex-PCR NGS assay; ctDNA status and CA-125 levels were correlated with clinical features and outcomes. RESULTS: Genomic profiling was performed on the entire cohort and was consistent with that seen in TCGA. In cohort A, ctDNA-positivity was observed in 73% (32/44) of presurgical samples and was higher in high nuclear grade disease. In cohort B and C, ctDNA was only detected in patients who relapsed (100% sensitivity and specificity) and preceded radiological findings by an average of 10 months. The presence of ctDNA at a single timepoint after completion of surgery +/- adjuvant chemotherapy and serially during surveillance was a strong predictor of relapse (HR:17.6, p = 0.001 and p < 0.0001, respectively), while CA-125 positivity was not (p = 0.113 and p = 0.056). CONCLUSIONS: The presence of ctDNA post-surgically is highly prognostic of reduced recurrence-free survival. CtDNA outperformed CA-125 in identifying patients at highest risk of recurrence. These results suggest that monitoring ctDNA could be beneficial in clinical decision-making for EOC patients.

Headache in the Pediatric Population: Focus on Migraine.

Pediatric headache is a common condition with significant impact on quality of life and ability to function in academic, social, and extracurricular activities. Most pediatric patients seen in primary care and neurology clinics with headache have primary headache disorders. Diagnosis is largely based on clinical history. Imaging is rarely needed in the absence of red flag features. Careful diagnosis is important to guide appropriate treatment. Treatment focuses on a biopsychosocial model integrating lifestyle, pharmacologic and nonpharmacologic treatment modalities. As few therapies are approved in the pediatric population, treatments are often used off-label based on evidence extrapolated from adult studies. Outcomes vary over time but are generally favorable when headache disorders are diagnosed promptly and managed in a multidisciplinary setting.

South Africa's Health Promotion Levy on Pricing and Acquisition of Beverages in Local Spazas and Supermarkets.

OBJECTIVE: In response to concern over rising sugar-sweetened beverage (SSB) consumption, in April 2018, South Africa became the first Sub-Saharan African country to implement an SSB tax. We assess changes in pricing and acquisition of beverages from local supermarkets and small stores among 18-39 year old adults living in one township in the Western Cape, before and after tax implementation. This study is among the first evaluations of an SSB tax on the local food environment in a low-income township. DESIGN: Store beverage pricing and participant surveys were cross-sectional, analyzed 1 month before and 11 months after implementation of the tax (March 2018 and March 2019). SETTING: Langa, Western Cape, South Africa. PARTICIPANTS: Surveyed participants were residents of Langa between 18-39 years old (N=2,693 in 2018 and N=2,520 in 2019). RESULTS: Prices of taxed SSBs increased significantly among small shops and supermarkets between 2018 and 2019. There were non-significant decreases in prices of untaxed beverages in small shops, but prices of untaxed beverages increased in supermarkets. Across all store types, there was a 9 percentage point decrease in the probability of purchasing regular soda weekly pre/post-implementation. Reductions in purchasing were larger in small shops than supermarkets. CONCLUSIONS: We found some differential impacts of the levy on pricing and acquisition of beverages by retailer type in one low-income township. As other Sub-Saharan African countries consider similar fiscal policies to curb soda consumption, obesity and related diseases, this work can be used to understand the implications of these policies in the retail setting.

Later high school start time is associated with lower migraine frequency in adolescents.

OBJECTIVE: To determine whether high school start time is associated with headache frequency in adolescents with migraine. BACKGROUND: Adolescence is marked by a physiologic delayed circadian phase, characterized by later bedtimes and wake times. The American Academy of Pediatrics (AAP) recommends that high schools start no earlier than 8:30 a.m., but most high schools in the United States start earlier. The study hypothesis was that adolescents with migraine whose high schools start at 8:30 a.m. or later (late group) would have lower headache frequency than those whose schools start earlier than 8:30 a.m. (early group). METHODS: This was a cross-sectional Internet survey study of US high schoolers with migraine recruited online through social media. Comparisons were made between the late group and the early group. The primary outcome measure was self-reported headache days/month. RESULTS: In total, 1012 respondents constituted the analytic set: n = 503 in the late group versus n = 509 in the early group. Mean (SD) self-reported headache days/month was 4.8 (4.6) versus 7.7 (6.1) in the late and early groups, respectively (p < 0.001); mean difference -2.9 (95% CI -2.2 to -3.6). Mean (SD) self-reported hours of sleep on a school night was 7.9 (0.9) versus 6.9 (1.3), p < 0.001. Adjusting for total hours of sleep, sex, taking a migraine preventive, days of acute medication use, hours of homework, grade level, and missing breakfast, mean (SD) self-reported headache days/month remained lower in the late group than in the early group: 5.8 (95% CI 5.3-6.2) versus 7.1 (95% CI 6.7-7.4), (p < 0.001); mean difference -1.3 (95% CI -1.9 to -0.7). CONCLUSION: Adolescents with migraine who attend high schools that follow AAP recommendations for start times have lower self-reported headache frequency than those whose high schools start before 8:30 a.m. If prospective studies confirm this finding, shifting to a later high school start time may be an effective strategy for migraine prevention in adolescents.

The intersection of COVID-19, school, and headaches: Problems and solutions.

OBJECTIVE: To equip clinicians with recommendations specific to concerns related to the novel coronavirus disease 2019 (COVID-19), which impact the physical, emotional, and social health of youth with headache disorders. BACKGROUND: COVID-19 has affected societies on a global scale including children and youth with chronic headache disorders. Many concerns are predicted to arise in the 2020-2021 school year, whether classes are conducted in-person or virtually. METHODS: Clinical impressions were combined with a review of the literature, although limited due to the recent nature of this issue. RESULTS: We describe recommendations to support caregivers and youth as they face changes expected with the return to school in the fall of 2020. CONCLUSION: Although there are significant concerns for caregivers and youth with migraine given the context of changes related to the pandemic, there are many recommendations that can help minimize exacerbations of the physical, emotional, and social health of youth with chronic migraine.

Post-traumatic Headache and Mild Traumatic Brain Injury: Brain Networks and Connectivity.

PURPOSE OF REVIEW: Post-traumatic headache (PTH) consequent to mild traumatic brain injury (mTBI) is a complex, multidimensional, chronic neurological disorder. The purpose of this review is to evaluate the current neuroimaging studies on mTBI and PTH with a specific focus on brain networks and connectivity patterns. RECENT FINDINGS: We present findings on PTH incidence and prevalence, as well as the latest neuroimaging research findings on mTBI and PTH. Additionally, we propose a new strategy in studying PTH following mTBI. The diversity and heterogeneity of pathophysiological mechanisms underlying mild traumatic brain injury pose unique challenges on how we interpret neuroimaging findings in PTH. Evaluating alterations in the intrinsic brain network connectivity patterns using novel imaging and analytical techniques may provide additional insights into PTH disease state and therefore inform effective treatment strategies.

Melatonin for Acute Treatment of Migraine in Children and Adolescents: A Pilot Randomized Trial.

OBJECTIVE: To determine what dose of melatonin is most effective for treating migraine acutely in children and adolescents. BACKGROUND: Acute migraine medications may not work for all patients and may cause side effects. Melatonin is effective for migraine prevention in adults and has been used acutely for procedural pain in children. Our goal was to determine whether a "high" or "low" dose of melatonin is more effective for treating migraine acutely in youth. METHODS: In this pilot, randomized, open-label, single-center, dose-finding trial, children and adolescents aged 4-17 years with episodic migraine were randomized to "high-dose" or "low-dose" dose melatonin (<40 kg: 4 mg vs. 1 mg; ≥40 kg: 8 mg vs. 2 mg). The primary outcome measure was change in mean pain score between time 0 and 2 hours. Secondary outcomes included 2-hour pain-relief and pain-freedom rates. RESULTS: Eighty-four participants (n = 42 per group) were enrolled in this study. Mean (SD) participant age was 11.8 (3.5) years and 55% (46/84) were female. Mean (SD) headache days/month was 5.6 (3.8). Sixty-six (79%) participants provided outcome data and were included in the analyses, n = 24 in the high-dose group and n = 22 in the low-dose group. The drop-out rate was 43% (18/42) in the high-dose group vs. 48% (20/42) in the low-dose group. Mean (SD) change in pain intensity at 2 hours was -2.7 (2.1) cm in the high-dose group vs. -2.3 (2.1) cm in the low-dose group (p = .581), a difference of 0.4 cm (95% CI: -1.17 to 1.92). Two-hour pain-freedom rate was 41% (7/17) vs. 27% (4/15) in the high-dose vs. low-dose groups (p = .415), and 2-hour pain-relief rate was 94% (16/17) vs. 80% (12/15), (p = .482). There were no serious adverse events. Napping occurred in the majority (67% (14/21) high dose vs. 47% (9/19) low dose). Higher mg/kg dose of melatonin and napping were each independently associated with greater headache benefit. CONCLUSIONS: As an acute treatment for pediatric migraine, both low and high doses of melatonin were associated with pain reduction; however, study drop-out was high. Higher dose and napping after treatment predicted greater benefit.

Modulating native GABAA receptors in medulloblastoma with positive allosteric benzodiazepine-derivatives induces cell death.

PURPOSE: Pediatric brain cancer medulloblastoma (MB) standard-of-care results in numerous comorbidities. MB is comprised of distinct molecular subgroups. Group 3 molecular subgroup patients have the highest relapse rates and after standard-of-care have a 20% survival. Group 3 tumors have high expression of GABRA5, which codes for the α5 subunit of the γ-aminobutyric acid type A receptor (GABAAR). We are advancing a therapeutic approach for group 3 based on GABAAR modulation using benzodiazepine-derivatives. METHODS: We performed analysis of GABR and MYC expression in MB tumors and used molecular, cell biological, and whole-cell electrophysiology approaches to establish presence of a functional 'druggable' GABAAR in group 3 cells. RESULTS: Analysis of expression of 763 MB tumors reveals that group 3 tumors share high subgroup-specific and correlative expression of GABR genes, which code for GABAAR subunits α5, ß3 and γ2 and 3. There are ~ 1000 functional α5-GABAARs per group 3 patient-derived cell that mediate a basal chloride-anion efflux of 2 × 109 ions/s. Benzodiazepines, designed to prefer α5-GABAAR, impair group 3 cell viability by enhancing chloride-anion efflux with subtle changes in their structure having significant impact on potency. A potent, non-toxic benzodiazepine ('KRM-II-08') binds to the α5-GABAAR (0.8 µM EC50) enhancing a chloride-anion efflux that induces mitochondrial membrane depolarization and in response, TP53 upregulation and p53, constitutively phosphorylated at S392, cytoplasmic localization. This correlates with pro-apoptotic Bcl-2-associated death promoter protein localization. CONCLUSION: GABRA5 expression can serve as a diagnostic biomarker for group 3 tumors, while α5-GABAAR is a therapeutic target for benzodiazepine binding, enhancing an ion imbalance that induces apoptosis.

Formative Research for an Innovative Smartphone Application to Improve Distribution of Healthy Foods to Corner Stores in Baltimore City.

We sought to collect information about the operations of wholesalers and store owner perceptions of smartphones to plan for and create a smartphone application that will facilitate the distribution of healthy foods to corner stores. In-depth interviews were conducted with wholesalers, corner store owners, distributors, and food environment experts in Baltimore City, Maryland, which included providing feedback for a mockup of the app. Store owners that were comfortable with smartphones liked the idea of the app because it was economically practical, culturally suitable, simple and easy to use, and provided a large variety of items at a fair or low price. We found that barriers to uptake among corner store owners would be high delivery costs, no foreign language capability, and a complicated user interface. This work will inform future projects that will utilize mHealth technology to improve distribution of healthier foods in food deserts.

Qualitative Exploration of a Smoking Cessation Trial for People Living With HIV in South Africa.

Introduction: In South Africa, people living with HIV have a high prevalence of smoking, which undermines the beneficial effects of antiretroviral therapy. However, little is known about barriers to smoking cessation and what interventions work for people living with HIV in this setting. Methods: A randomized trial comparing intensive anti-smoking counseling versus counseling and nicotine replacement therapy was recently concluded in Klerksdorp, South Africa. In a post-trial follow-up, 23 in-depth interviews with patients and one focus group discussion with counselors from the trial were conducted. A codebook was developed and codes were applied to the transcripts, which were analyzed using a thematic analysis. Results: Barriers at the economic, social/interpersonal, and individual levels induced stress, which hindered smoking cessation. Economic stressors included unemployment and poverty. Social or interpersonal stressors were lack of social support for quitting smoking and lack of social support due to having HIV. Individual stressors were traumatic life events. Alcohol was used to cope with stress and frequently co-occurred with smoking. Managing cravings was a barrier unrelated to stress. Participants proposed income and employment opportunities, group counseling, and more frequent counseling as solutions to address stressors at different levels. Nicotine replacement therapy was helpful to mitigate cravings. Conclusions: Future smoking cessation interventions need to target barriers at multiple levels. Increasing the supply and duration of nicotine replacement therapy may increase its effectiveness. Other behavioral approaches such as group counseling or peer counseling could hold promise in this setting but need to be tested for efficacy through randomized controlled trials. Implications: To our knowledge, this is the first qualitative study examining barriers to smoking cessation for people living with HIV in South Africa. Smoking is highly prevalent among people with HIV in South Africa and cessation interventions are urgently needed. A better understanding of barriers to smoking cessation that people with HIV face will lead to the development of contextually appropriate interventions. This study also provides feedback on interventions from a recently concluded smoking cessation randomized trial and will help guide the design of future smoking cessation trials.

Social Risk and Resilience Factors in Adolescent Chronic Pain: Examining the Role of Parents and Peers.

Objective: The current study focuses on social risk and resilience in an adolescent population with chronic pain. Prior research identifies parental cognitions and behaviors as influential in youths' experiences of chronic pain and pain-related disability. Adolescent development is characterized by greater autonomy from parents and an increased emphasis on peer relationships. Study aims explore the potential protective effect of high-quality adolescent peer relationships on associations between parent and adolescent cognitive and behavioral responses to pain. Method: 238 adolescents with mixed-etiology chronic pain and their parents completed Pediatric Collaborative Health Outcomes Information Registry (Peds-CHOIR) electronic questionnaires prior to their initial visit to a tertiary pediatric pain clinic. Variables in this study include parent catastrophizing, parent protective behavior, adolescent peer relationship quality, adolescent catastrophizing, adolescent functional impairment, and demographic and pain characteristics. Results: As expected, associations between parent and adolescent cognitive and behavioral pain responses were moderated by peer relationship quality. Contrary to expectations, for adolescents endorsing low-quality peer relationships, maladaptive adolescent outcomes were elevated across levels of parental cognitions and behaviors. For adolescents endorsing high-quality peer relationships, adolescent and parent pain responses were linearly related. Conclusions: This study highlights the salience of both family and peer processes in functional outcomes among adolescents with chronic pain. Results suggest that adolescents' adaptive responses to chronic pain may be best supported by the simultaneous presence of adaptive parenting and high-quality peer relationships. Understanding the larger social context in which an adolescent exists is informative in specifying models that predict adaptive outcomes or magnify risks.

A prospective study comparing perioperative anxiety and posthospital behavior in children with autism spectrum disorder vs typically developing children undergoing outpatient surgery.

BACKGROUND: Research describing the experience of youth with autism spectrum disorders in the perioperative setting is limited. This study compared youth with autism spectrum disorder to typically developing children in the perioperative setting and examined group differences in: child anxiety, parent anxiety, premedication patterns, induction compliance, and changes in behavior postprocedure. METHODS: Participants were 60 youth (32 with autism spectrum disorder, 28 typically developing) of ages 2-19 years undergoing outpatient surgery and their parents. Parents and research assistants rated children's anxiety at 3 time points (waiting room, preoperative holding, separation), and parents rated their own anxiety in the waiting room and at separation. The anesthesiologist rated induction compliance. Postprocedure behavior change was assessed via phone survey 1 and 7 days postprocedure. Analyses examined group differences in anxiety, medication patterns, and behavior. RESULTS: Children with autism spectrum disorder had higher research assistant reported anxiety than typically developing youth in the holding room only. There were no group differences in parent report of their own anxiety or their child's anxiety across time points. Compared to typically developing youth, children with autism spectrum disorder were more likely to receive a premedication (including nonstandard premedication), and had poorer induction compliance. Groups did not differ on posthospital behavior change 1 or 7 days postsurgery. CONCLUSION: Findings revealed ratings of anxiety in youth with and without autism spectrum disorder facing surgery varied by reporter and setting, highlighting the importance of using multiple reporters in research of youth with autism spectrum disorder in the perioperative period. Furthermore, while results showed group differences in premedication patterns and induction compliance, groups did not differ in level of negative behavior change after surgery. Future research can examine how individual differences in youth with autism impact anxiety in the perioperative setting and degree of behavior change postprocedure.

A mixed methods assessment of the barriers and readiness for meeting the SNAP depth of stock requirements in Baltimore's small food stores.

We sought to understand Baltimore corner store owners' awareness of and readiness for the then-approved Supplemental Nutrition Assistance Program depth of stock requirements and assess potential barriers and solutions. In-depth interviews and stocking observations were conducted in 17 corner stores in low-income food deserts of Baltimore City. Corner store owners conveyed little to no awareness of the pending depth of stock changes. Only two stores were currently ready for the requirements. Low customer demand, high amounts of potential spoilage, and unfair pricing at the wholesaler were identified by store owners as barriers to stocking required foods.

Synergistic role of protein phosphatase inhibitor 1 and sarco/endoplasmic reticulum Ca2+ -ATPase in the acquisition of the contractile phenotype of arterial smooth muscle cells.

BACKGROUND: Phenotypic modulation or switching of vascular smooth muscle cells from a contractile/quiescent to a proliferative/synthetic phenotype plays a key role in vascular proliferative disorders such as atherosclerosis and restenosis. Although several calcium handling proteins that control differentiation of smooth muscle cells have been identified, the role of protein phosphatase inhibitor 1 (I-1) in the acquisition or maintenance of the contractile phenotype modulation remains unknown. METHODS AND RESULTS: In human coronary arteries, I-1 and sarco/endoplasmic reticulum Ca2+ -ATPase expression is specific to contractile vascular smooth muscle cells. In synthetic cultured human coronary artery smooth muscle cells, protein phosphatase inhibitor 1 (I-1 target) is highly expressed, leading to a decrease in phospholamban phosphorylation, sarco/endoplasmic reticulum Ca2+ -ATPase, and cAMP-responsive element binding activity. I-1 knockout mice lack phospholamban phosphorylation and exhibit vascular smooth muscle cell arrest in the synthetic state with excessive neointimal proliferation after carotid injury, as well as significant modifications of contractile properties and relaxant response to acetylcholine of femoral artery in vivo. Constitutively active I-1 gene transfer decreased neointimal formation in an angioplasty rat model by preventing vascular smooth muscle cell contractile to synthetic phenotype change. CONCLUSIONS: I-1 and sarco/endoplasmic reticulum Ca2+ -ATPase synergistically induce the vascular smooth muscle cell contractile phenotype. Gene transfer of constitutively active I-1 is a promising therapeutic strategy for preventing vascular proliferative disorders.

Similar survival in patients following heart transplantation receiving induction therapy using daclizumab vs. basiliximab.

BACKGROUND: Induction therapy with interleukin-2 receptor antagonists has been established as an effective immunosuppressive strategy in the management of heart transplant (HTx) recipients. We compared outcomes following HTx in patients receiving basiliximab, daclizumab, or no induction therapy. METHODS AND RESULTS: We investigated post-transplant prognosis of patients receiving basiliximab (n=67), daclizumab (n=98) or no induction therapy (n=70). Patients treated with daclizumab (50.3 ± 14.7 years) were younger than those receiving basiliximab (55.8 ± 11.2 years) or no induction therapy (54.9 ± 14.1 years; both P<0.05). Patients receiving either induction therapy showed better survival 1 year after HTx (95%) than those without induction therapy (82%; P<0.001). Survival was similar between patients receiving basiliximab and daclizumab. The incidence of acute cellular or antibody-mediated rejections did not differ among the groups. The main reason that patients did not receive induction therapy was ongoing infection (65.7%), which was more common in patients on ventricular assist device (VAD) support than those without VAD (76.1% vs. 45.8%; P=0.004). The VAD-related infection rate in the entire study cohort was 29.7% (35/118 VAD recipients). CONCLUSIONS: Survival following HTx was worse in patients not receiving induction therapy. No differences were noted in survival or the incidence of rejection between the daclizumab- and basiliximab-treated groups. Induction therapy was less used in patients with infection, which was related to prior VAD support.

A peer-nomination assessment of electronic forms of aggression and victimization.

The perpetration and receipt of electronic aggression have largely been assessed with self-report questionnaires. Using a sample of 573 adolescents, the current study compared the psychometric properties of a peer-nomination measure of electronic aggression and victimization to the more widely used self-report approach. Estimates of the reliability, stability, and concordance of peer- and self-report assessments were adequate, mirroring those from research on aggressive exchanges in school. Analyses of validity and utility revealed that peer-nominations, compared to self-reports, provide overlapping and distinct information on adolescents' social, emotional, and academic adjustment. Overall, these findings provide evidence that peer-nominations are a reliable, valid, and useful means for measuring electronic aggression and victimization. Future work will benefit from their incorporation into multi-method assessments.

Run, walk, cheer or volunteer: a patient and public involvement survey.

Background: Children with chronic diseases have been reported to participate in less regular physical activity (PA) than peers without chronic diseases; and less than recommended in guidelines. Sheffield Children's Foundation Trust (SCFT) is an Active Hospitals pilot site, exploring options to facilitate PA for all children. One option is collaboration with Junior Parkrun: a free, weekly 2 km running event for children. The team investigated whether Junior Parkrun was of interest to guardians of children attending SCFT to increase PA. Aims: This patient and public involvement survey assessed perceptions of PA for children attending SCFT according to their accompanying guardians. This will inform a possible collaboration between SCFT and Junior Parkrun. Methods: A three-part, 14-question survey was developed, including demographics (age, ethnicity, postcode); perceptions of PA (barriers and facilitators); PA behaviours self-reported on Likert scales; and perceptions of Junior Parkrun. Guardians were asked whether they and their child would be interested in attending Junior Parkrun with SCFT staff support. This was distributed to guardians of children attending outpatient appointments. Results: 126 guardians responded. The average age of child was 10 years 10 months. 29.1% of guardians supported daily PA for their child. Almost half of respondents reported their child would be interested in attending Junior Parkrun. Of those not interested, the most common reason was travel. Conclusion: The findings highlighted PA barriers perceived by guardians, and identified that almost half of respondents would be interested in attending Junior Parkrun. A collaboration between Junior Parkrun and SCFT could be explored.