Sleep insufficiency and bedtime irregularity in children with ADHD: A population-based analysis.

BACKGROUND: Sleep is impaired in children with attention-deficit/hyperactivity disorder (ADHD). However, population-based examination of indicators of sleep insufficiency and bedtime irregularity is limited. This investigation examined associations between ADHD, weeknight sleep insufficiency, and bedtime irregularity in a nationally-representative child sample, and indicators of these sleep outcomes in ADHD. METHODS: Parents of children aged 3-17 years with ADHD (n = 7671) were surveyed through the 2020-2021 National Survey of Children's Health. Inverse probability of treatment weighting generated a weighted matched control sample (n = 51,572). Weighted generalized linear models were performed without and with age-stratification to examine associations between ADHD and sleep, adjusting for sociodemographics in the full sample, and between nineteen sociodemographic and clinical variables and sleep in ADHD. RESULTS: Having ADHD was associated with increased odds of sleep insufficiency and bedtime irregularity relative to controls, even after adjusting for sociodemographic variables. In ADHD, older age was associated with lower sleep insufficiency and greater bedtime irregularity. Black race, increased poverty, higher ADHD severity, depression, and increased screen time were associated with greater sleep insufficiency and bedtime irregularity. Adverse childhood experiences (ACEs) were associated with greater sleep insufficiency. Behavioral/conduct problems, female sex, and absence of both ADHD medication use and ASD diagnosis were associated with poorer bedtime irregularity. Age-stratified results are reported in text. CONCLUSIONS: Children with ADHD face heightened risk for insufficient sleep and irregular bedtimes. Findings suggest intervention targets (e.g., Black race, poverty, depression, screen time) to improve both sleep insufficiency and bedtime irregularity. Results highlight ACEs and behavioral/conduct problems as targets to improve sleep insufficiency and bedtime regularity, respectively. Age-stratified findings are discussed.

Pulmonary responses following cardiac rehabilitation and the relationship with functional outcomes in children and young adults with heart disease.

Introduction: Patients with congenital heart disease (CHD) often have pulmonary abnormalities and exercise intolerance following cardiac surgery. Cardiac rehabilitation (CR) improves exercise capacity in patients with CHD, but minimal study has been performed to see if resting and dynamic pulmonary performance improves following CR in those with prior cardiac surgery. Methods: This was a retrospective cohort study of all patients who completed ≥12 weeks of CR from 2018 through 2022. Demographic, cardiopulmonary exercise test (CPET), spirometry, 6-minute walk, functional strength measures, and outcomes data were collected. Data are presented as median[IQR]. A Student's t-test was used for comparisons between groups and serial measurements were measured with a paired t-test. A p < 0.05 was considered significant. Results: There were a total of 37 patients [age 16.7 (14.2-20.1) years; 46% male] included. Patients with prior surgery (n = 26) were more likely to have abnormal spirometry data than those without heart disease (n = 11) (forced vital capacity [FVC] 76.7 [69.1-84.3]% vs. 96.4 [88.1-104.7]%, p = 0.002), but neither group experienced a significant change in spirometry. On CPET, peak oxygen consumption increased but there was no change in other pulmonary measures during exercise. Percent predicted FVC correlated with hand grip strength (r = 0.57, p = 0.0003) and percent predicted oxygen consumption (r = 0.43, p = 0.009). The number of prior sternotomies showed negative associations with both percent predicted FVC (r = -0.43, p = 0.04) and FEV1 (r = -0.47, p = 0.02). Discussion: Youth and young adults with a prior history of cardiac surgery have resting and dynamic pulmonary abnormalities that do not improve following CR. Multiple sternotomies are associated with worse pulmonary function.

Vestibular evaluation with video head impulse test in pediatric cochlear implant patients.

BACKGROUND: The cochlear implant (CI) is effective for rehabilitating patients with severe to profound sensorineural hearing loss. However, its placement and use have been associated with various complications, such as those affecting the vestibular system. The objective of this study was to compare vestibular function using the video head impulse test (vHIT) in pediatric patients before and after CI placement. METHODS: A descriptive and retrospective study was conducted. The outcomes of 11 pediatric patients of both sexes with a history of profound hearing loss were evaluated. The results of vestibular-ocular reflex (VOR) gain, saccades, asymmetry, Pérez Rey (PR) index, and VOR/saccade ratio for both ears obtained by the vHIT test before and after CI placement were compared. RESULTS: Of the 11 patients evaluated, the VOR gain showed that 81.8% had normal function, 18.2% had hypofunction, and no patients had hyperfunction before implantation. No statistically significant differences were found when compared with post-implant off and post-implant on conditions (p > 0.05). The extracted variables, asymmetry, PR index, and the VOR/saccades ratio also showed no statistically significant differences between the pre- and post-implant conditions, whether off or on. CONCLUSIONS: The vestibular function of pediatric patients did not show significant changes before and after CI placement. The vHIT test is a valuable tool for assessing vestibular function and could be considered a criterion for surgical and rehabilitation decisions in patients undergoing CI placement.

INTRODUCCIÓN: El implante coclear es un dispositivo eficaz para la rehabilitación de pacientes con hipoacusia neurosensorial severa a profunda. Sin embargo, su colocación y uso se ha asociado a diversas complicaciones, entre ellas a nivel del sistema vestibular. El objetivo del presente estudio fue comparar la función vestibular mediante la prueba de videoimpulso cefálico (vHIT) de pacientes pediátricos antes y después de la colocación del implante coclear. MÉTODOS: Se llevó a cabo un estudio descriptivo y retrospectivo. Se evaluaron los resultados de 11 pacientes pediátricos de ambos sexos con antecedente de hipoacusia profunda. Se compararon los resultados de ganancia del VOR, sacadas, asimetría, índice PR así como la relación VOR/sacadas para ambos oídos obtenidos mediante la prueba vHIT antes y después de la colocación del implante coclear. RESULTADOS: De los 11 pacientes evaluados, la ganancia del VOR mostró que el 81.8% tenía normofunción, 18.2% hipofunción y ningún paciente hiperfunción antes del implante. Al compararlo con la ganancia post implante apagado y post implante encendido no se encontraron diferencias estadísticamente significativas (p > 0.05). Las variables sacadas, asimetría, índice PR así como la relación VOR/sacadas tampoco mostraron diferencias estadísticamente significativas entre las condiciones pre y pos implante ya sea apagado o encendido. CONCLUSIONES: La función vestibular de pacientes pediátricos no mostró cambios significativos previo y posterior a la colocación del implante coclear. La prueba vHIT es una herramienta útil que permite evaluar la función vestibular y que podría considerarse como criterio para tomar decisiones quirúrgicas en pacientes que se encuentran en protocolo para implante coclear.

High-dose chemotherapy and peripheral blood stem cell transplantation as salvage therapy in primary mediastinal nonseminomatous germ cell tumors: The Indiana University experience.

BACKGROUND: Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high-dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. METHODS: The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first-line cisplatin-based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method. Medians with 95% confidence intervals were also calculated along with 2-year probabilities. RESULTS: The median age at HDCT was 30 years (range, 18-61 years). With a median follow-up of 4.7 years (range, 1-14 years), the 2-year progression-free survival rate was 31% (95% confidence interval, 16%-47%), and the 2-year overall survival rate was 35% (95% confidence interval, 19%-52%). At last follow-up, nine patients (28%) remained without evidence of disease, including two platinum-refractory patients and two patients who were receiving HDCT as third-line therapy. There were three treatment-related deaths. CONCLUSIONS: Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum-refractory and third-line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population.

A Network Approach to Understanding the Role of Executive Functioning and Alpha Oscillations in Inattention and Hyperactivity-Impulsivity Symptoms of ADHD.

OBJECTIVE: ADHD is a prevalent neurodevelopmental disorder characterized by symptoms of inattention and hyperactivity-impulsivity. Impairments in executive functioning (EF) are central to models of ADHD, while alpha-band spectral power event-related decreases (ERD) have emerged as a putative electroencephalography (EEG) biomarker of EF in ADHD. Little is known about the roles of EF and alpha ERD and their interactions with symptoms of ADHD. METHOD: We estimated network models of ADHD symptoms and integrated alpha ERD measures into the symptom network. RESULTS: EF emerges as a bridge network node connecting alpha ERD and the hyperactivity/impulsivity and inattention symptoms. We found that EF most closely relates to a subset of symptoms, namely the motoric symptoms, "seat" (difficulty staying seated), and "runs" (running or climbing excessively). CONCLUSIONS: EF functions as a bridge node connecting alpha ERD and the ADHD symptom network. Motoric-type symptoms and EF deficits may constitute important nodes in the interplay between behavior/symptoms, cognition, and neurophysiological markers of ADHD.

Polymer Nanocomposite Sensors with Improved Piezoelectric Properties through Additive Manufacturing.

Additive manufacturing (AM) technology has recently seen increased utilization due to its versatility in using functional materials, offering a new pathway for next-generation conformal electronics in the smart sensor field. However, the limited availability of polymer-based ultraviolet (UV)-curable materials with enhanced piezoelectric properties necessitates the development of a tailorable process suitable for 3D printing. This paper investigates the structural, thermal, rheological, mechanical, and piezoelectric properties of a newly developed sensor resin material. The polymer resin is based on polyvinylidene fluoride (PVDF) as a matrix, mixed with constituents enabling UV curability, and boron nitride nanotubes (BNNTs) are added to form a nanocomposite resin. The results demonstrate the successful micro-scale printability of the developed polymer and nanocomposite resins using a liquid crystal display (LCD)-based 3D printer. Additionally, incorporating BNNTs into the polymer matrix enhanced the piezoelectric properties, with an increase in the voltage response by up to 50.13%. This work provides new insights for the development of 3D printable flexible sensor devices and energy harvesting systems.

Mortality with concurrent treatment with gabapentin and opioids among people with spine diagnoses in the U.S. Medicare population: a propensity-matched cohort study.

IMPORTANCE: Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. Concurrent gabapentin and opioid prescriptions are commonly reported in retrospective studies of opioid-related overdose deaths. OBJECTIVE: To determine whether people who filled gabapentin and opioid prescriptions concurrently ('gabapentin + opioids') had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently ('TCAs/duloxetine + opioids'). We hypothesized that people treated with gabapentin + opioids would have higher mortality rates compared to people treated with TCAs/duloxetine + opioids. DESIGN: Propensity score-matched cohort study with an incident user, active control design. The median (maximum) follow-up was 45 (1093) days. SETTING: Population-based. PARTICIPANTS: Medicare beneficiaries with spine-related diagnoses 2017-2019. The primary analysis included those who concurrently (within 30 days) filled at least 1 incident gabapentin + at least 1 opioid or at least 1 incident TCA/duloxetine + at least 1 opioid. EXPOSURES: People treated with gabapentin + opioids (n=67,133) were matched on demographic and clinical factors in a 1:1 ratio to people treated with TCAs/duloxetine + opioids (n=67,133). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at any time. A secondary outcome was occurrence of a major medical complication at any time. RESULTS: Among 134,266 participants (median age 73.4 years; 66.7% female), 2360 died before the end of follow-up. No difference in mortality was observed between groups (adjusted hazard ratio (HR) and 95% confidence interval (CI) for gabapentin + opioids was 0.98 (0.90, 1.06); p=0.63). However, people treated with gabapentin + opioids were at slightly increased risk of a major medical complication (1.02 (1.00, 1.04); p=0.03) compared to those treated with TCAs/duloxetine + opioids. Results were similar in analyses (a) restricted to less than or = 30-day follow-up and (b) that required at least 2 fills of each prescription. CONCLUSIONS AND RELEVANCE: When treating pain in older adults taking opioids, the addition of gabapentin did not increase mortality risk relative to addition of TCAs or duloxetine. However, providers should be cognizant of a small increased risk of major medical complications among opioid users initiating gabapentin compared to those initiating TCAs or duloxetine.

Midlife health crisis of former competitive athletes: dissecting their experiences via qualitative study.

Sports participation confers many health benefits yet greatly increases injury risk. Long-term health outcomes in former athletes and transition to life after competitive sports are understudied. Ending a sport may pose physical and psychosocial challenges. The purpose was to determine the lived experiences of former competitive athletes and how their sports participation impacted their long-term health and well-being. Former college varsity athletes participated in semistructured interviews focusing on their experiences, including past and current health, the impact of injuries, activity, exercise, diet and transition to life after competitive sport. Thematic analysis was completed using a collaborative, iterative process. Thirty-one (16 female, 15 male) former college athletes aged 51.3±7.4 years were interviewed. Six themes emerged: (1) lifelong athlete identity; (2) structure, support and challenges of the college athlete experience; (3) a big transition to life beyond competitive sport; (4) impact of competitive sport on long-term health; (5) facilitators and barriers to long-term health after sport and (6) transferable life skills. Continuing sports eased the transition for many but often delayed their postathlete void. Challenges included managing pain and prior injury (eg, If I didn't have my knee injury, I would definitely be more active), reducing energy needs and intake (eg, When I was an athlete, I could eat anything; and unfortunately, that's carried into my regular life), lack of accountability, changed identity and lost resources and social support. Participants suggested a programme, toolkit, mentoring or exit course to facilitate the transition. While former athletes benefit from transferrable life skills and often continue sports and exercise, they face unique challenges such as managing pain and prior injury, staying active, reducing energy intake and changing identity. Future research should develop and evaluate a toolkit, programme and other resources to facilitate life after ending competitive sports under 'normal' conditions (eg, retirement) and after a career-ending injury.

Alpha event-related decreases during encoding in adults with ADHD - An investigation of sustained attention and working memory processes.

BACKGROUND: Executive functioning deficits are central to established neuropsychological models of ADHD. Oscillatory activity, particularly the alpha rhythm (8-12 Hz) has been associated with cognitive impairments in ADHD. However, most studies to date examined such neural mechanisms underlying executive dysfunction in children and adolescents with ADHD, raising the question of whether and to what extent those ADHD-related working memory impairments are still present in adults. To this end, the current study aimed to investigate the role of alpha event-related decreases (ERD) during working memory processes in adults with and without ADHD. METHODS: We collected electroencephalographic (EEG) data from 85 adults with a lifetime diagnosis of ADHD and 105 controls (aged 32-64), while they performed a continuous performance (CPT) and a spatial delayed response working memory task (SDRT). Time-frequency and independent component analysis (ICA) was used to identify alpha (8-12 Hz) clusters to examine group and condition effects during the temporal profile of sustained attention and working memory processes (encoding, maintenance, retrieval), loads (low and high) and trial type (go and nogo). RESULTS: Individuals with ADHD exhibited higher reaction time-variability in SDRT, and slower response times in SDRT and CPT, despite no differences in task accuracy. Although working memory load was associated with stronger alpha ERD in both tasks and both groups (ADHD, controls), we found no consistent evidence for attenuated alpha ERD in adults with ADHD, failing to replicate effects reported in children. In contrast, when looking at the whole sample, the correlations of alpha power during encoding with inattention and hyperactivity-impulsivity symptoms were significant, replicating prior findings in children with ADHD, but suggesting an alternate source for these effects in adults. CONCLUSIONS: Our results corroborate the robustness of alpha as a marker of visual attention and suggest that occipital alpha ERD normalizes in adulthood, but with unique contributions of centro-occipital alpha ERD, suggesting a secondary source. This implies that deviations in processes other than previously reported visuospatial cortex engagement may account for the persistent symptoms and cognitive deficits in adults with a history of ADHD.

Contextual barriers and enablers to establishing an addiction-focused consultation team for hospitalized adults with opioid use disorder.

BACKGROUND: Hospitalization presents an opportunity to begin people with opioid use disorder (OUD) on medications for opioid use disorder (MOUD) and link them to care after discharge; regrettably, people admitted to the hospital with an underlying OUD typically do not receive MOUD and are not connected with subsequent treatment for their condition. To address this gap, we launched a multi-site randomized controlled trial to test the effectiveness of a hospital-based addiction consultation team (the Substance Use Treatment and Recovery Team (START)) consisting of an addiction medicine specialist and care manager team that provide collaborative care and a specified intervention to people with OUD during the inpatient stay. Successful implementation of new practices can be impacted by organizational context, though no previous studies have examined context prior to implementation of addiction consultation services (ACS). This study assessed pre-implementation context for implementing a specialized ACS and tailoring it accordingly. METHODS: We conducted semi-structured interviews with hospital administrators, physicians, physician assistants, nurses, and social workers at the three study sites between April and August 2021 before the launch of the pragmatic trial. Using an analytical framework based on the Consolidated Framework for Implementation Research, we completed a thematic analysis of interview data to understand potential barriers or enablers and perceptions about acceptability and feasibility. RESULTS: We interviewed 28 participants across three sites. The following themes emerged across sites: (1) START is an urgently needed model for people with OUD; (2) Intervention adaptations are recommended to meet local and cultural needs; (3) Linking people with OUD to community clinicians is a highly needed component of START; (4) It is important to engage stakeholders across departments and roles throughout implementation. Across sites, participants generally saw a need for change from usual care to support people with OUD, and thought the START was acceptable and feasible to implement. Differences among sites included tailoring the START to support the needs of varying patient populations and different perceptions of the prevalence of OUD. CONCLUSIONS: Hospitals planning to implement an ACS in the inpatient setting may wish to engage in a systematic pre-implementation contextual assessment using a similar framework to understand and address potential barriers and contextual factors that may impact implementation. Pre-implementation work can help ensure the ACS and other new practices fit within each unique hospital context.

From Consensus Statement to Pills to Pixels: New Innovations in Attention-Deficit/Hyperactivity Disorder Care.

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations.

Sex Differences in Track and Field Elite Youth.

PURPOSE: To understand athletic performance before and after puberty, this study determined: 1) the age at which the sex difference increases among elite youth track and field athletes for running and jumping events; and 2) whether there is a sex difference in performance prior to ages associated with puberty among elite youth athletes. METHODS: Track and field records of elite USA male and female youth (7-18 years) across three years (2019, 2021, and 2022) were collected from an online database ( athletic.net ). The top 50 performances were recorded for 100 m, 200 m, 400 m, and 800 m track running, long jump, and high jump. RESULTS: Males ran faster than females at every age in the 100, 200, 400 and 800 m ( P < 0.001). When combining all running events, the sex difference (%) was 4.0 ± 1.7% between 7-12 years and increased to 6.3 ± 1.1% at 13 years, and 12.6 ± 1.8% at 18 years ( P < 0.001). Similarly, males jumped higher and farther than females at every age ( P < 0.001). For long jump, the sex difference was 6.8 ± 2.8% between 7-12 years, increasing to 8.5 ± 1.7% at 13 years, and 22.7 ± 1.4% at 18 years ( P < 0.001). For high jump, the sex difference was 5.3 ± 5.2% between 7-12 years, increasing to 12.4 ± 2.9% at 15 years, and 18.4 ± 2.04% at 18 years ( P < 0.001). CONCLUSIONS: Prior to 12 years of age in elite youth track and field athletes, there was a consistent and significant sex difference of ~5%, such that males ran faster and jumped higher and farther than females. The magnitude of the sex difference in performance increased markedly at 12-13 years for running and long jump and 14 years for high jump and thus was more pronounced after ages associated with puberty.

Preparing Nurse Practitioner Graduates for the Transition to Practice.

BACKGROUND: Educators ensure that nurse practitioner (NP) students meet core competencies prior to graduation. Post-graduation, students navigate certification, licensure, resume building, and job searches. A statewide virtual conference was developed to help students during the transition to advanced nursing practice. METHOD: Information was presented on professional role development, resume writing, interviewing, licensure, certification, contract negotiation, and transitioning to a provider role. RESULTS: Nearly all participants (92%) were able to describe the status of NP practice and licensure requirements. Most attendees (90%) valued the insight shared by panelists. Many students (88%) felt more prepared to negotiate a contract. CONCLUSION: Current educational programs lack the time to thoroughly address NP graduates' learning needs regarding transition to practice. A partnership between faculties and a state professional organization is an innovative approach to meet students' educational desires. Delivery of a virtual conference during the pandemic proved to be cost effective. [J Nurs Educ. 2024;63(X):XXX-XXX.].

Hormonal Basis of Biological Sex Differences in Human Athletic Performance.

Biological sex is a primary determinant of athletic human performance involving strength, power, speed, and aerobic endurance and is more predictive of athletic performance than gender. This perspective article highlights 3 key medical and physiological insights related to recent evolving research into the sex differences in human physical performance: (1) sex and gender are not the same; (2) males and females exhibit profound differences in physical performance with males outperforming females in events and sports involving strength, power, speed, and aerobic endurance; (3) endogenous testosterone underpins sex differences in human physical performance with questions remaining on the roles of minipuberty in the sex differences in performance in prepubescent youth and the presence of the Y chromosome (SRY gene expression) in males, on athletic performance across all ages. Last, females are underrepresented as participants in biomedical research, which has led to a historical dearth of information on the mechanisms for sex differences in human physical performance and the capabilities of the female body. Collectively, greater effort and resources are needed to address the hormonal mechanisms for biological sex differences in human athletic performance before and after puberty.

Comparing Single Tooth Implant Placement With and Without Allogenic Soft Tissue Augmentation. A Randomized Clinical Trial.

OBJECTIVE: To explore the effect of adding an allogenic soft tissue graft at time of single implant placement using a fully digital workflow for single implant placement and restoration without making either analog or digital impressions. MATERIALS AND METHODS: A prospective randomized clinical study was performed enrolling thirtynine participants requiring single tooth implant randomized into (+ graft) group which received an allogenic dermal graft at the time of implant placement (n=19), or (- graft) group (n=20). A fully digital surgical and restorative protocol was implemented. Intraoral scans were taken before implant placement (T0), at time of final crown delivery (T1) and at one-year post placement (T2). Intraoral scans were aligned using Geomagic Control X 2020 software), linear and volumetric changes in buccal tissues were measured at T0, T1 and T2. Implant survival, probing depths, and complications were recorded. Participants were asked to complete an OHIP-14 survey at T0 and T2. Marginal bone levels were measured at T0 and T2 on peri-apical x-rays. RESULTS: 39 participants completed surgery and restoration in incisor, canine, premolar and molar positions. Two early failures were recorded in central incisor positions (95% survival). Crown delivery without complication from the digital workflow (impressionless) was achieved for 36/39 of cases (92%) with implant depth control being implicated as the chief challenge. Thirtyseven participants attended the one-year follow-up visit. Both groups showed gain in buccal tissues thickness without significant differences between the two groups for both linear and volumetric measurements (P>0.05). Soft tissue grafting was associated with minimal added morbidity. The interproximal marginal bone changes recorded were -0.16mm mesial and - 0.12mm distal for the graft group and -0.01mm mesial and -0.11mm distal for the non-graft group (p=0.07 for mesial and 0.83 for distal). OHIP score was significantly reduced at T2 compared to T0 (P=0.003) for the entire cohort. CONCLUSIONS: The augmentation of alveolar mucosa on the buccal aspect of single tooth implants is associated with clinically favorable outcomes. A fully digital workflow has been validated to permit crown delivery on CAD/CAM abutments without implant impressions.

Endothelial-to-Mesenchymal Transition in Human and Murine Models of Congenital Diaphragmatic Hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a complex congenital disorder, characterized by pulmonary hypertension (PH) and hypoplasia. PH secondary to CDH (CDH-PH) features devastating morbidity and mortality (25-30%) among neonates. An unmet need is determining mechanisms triggering CDH-PH to save infants. Prior data suggest abnormal remodeling of the pulmonary vascular extracellular matrix (ECM), presumed to be driven by endothelial-to-mesenchymal transition (EndoMT), hinders postnatal vasodilation and limits anti-PH therapy in CDH. There are limited data on the role of EndoMT in CDH-PH. METHODS: The purpose of the study was to investigate how EndoMT contributes to CDH-PH by identifying cells undergoing EndoMT noted by alpha smooth muscle actin (α-SMA) expression in human umbilical vein endothelial cells (HUVECs) and lung tissue obtained from murine pups using the nitrofen model. N = 8 CDH, N = 8 control HUVECs were stained for α-SMA and CD31 after being exposed for 24 h to TGFB, a known EndoMT promoter. N = 8 nitrofen, N = 8 control murine pup lungs were also stained for α-SMA and CD31. α-SMA and CD31 expression was quantified in HUVECs and murine tissue using Fiji imaging software and normalized to the total number of cells per slide noted by DAPI staining. RESULTS: CDH HUVECs demonstrated a 1.1-fold increase in α-SMA expression (p = 0.02). The murine model did not show statistical significance between nitrofen and control pup lungs; however, there was a 0.4-fold increase in α-SMA expression with a 0.8-fold decrease in CD31 expression in the nitrofen pup lungs when compared to controls. CONCLUSION: These results suggest that EndoMT could potentially play a role in the ECM remodeling seen in CDH-PH.

Influence of visual feedback and cognitive challenge on the age-related changes in force steadiness.

Force steadiness can be influenced by visual feedback as well as presence of a cognitive tasks and potentially differs with age and sex. This study determined the impact of altered visual feedback on force steadiness in the presence of a difficult cognitive challenge in young and older men and women. Forty-nine young (19-30 yr; 25 women, 24 men) and 25 older (60-85 yr; 15 women; 10 men) performed low force (5% of maximum) static contractions with the elbow flexor muscles in the presence and absence of a cognitive challenge (counting backwards by 13) either with low or high visual feedback gain. The cognitive challenge reduced force steadiness (increased force fluctuation amplitude) particularly in women (cognitive challenge × sex: P < 0.05) and older individuals (cognitive challenge × age: P < 0.05). Force steadiness improved with high-gain visual feedback compared with low-gain visual feedback (P < 0.01) for all groups (all interactions: P > 0.05). Manipulation of visual feedback had no influence on the reduced force steadiness in presence of the cognitive challenge for all groups (all P > 0.05). These findings indicate that older individuals and women have greater risk of impaired motor performance of the upper extremity if steadiness is required during a low-force static contraction. Manipulation of visual feedback had minimal effects on the reduced force steadiness in presence of a difficult cognitive challenge.

Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-Ascending Doses of Sunobinop in Healthy Participants.

Sunobinop is an investigational, potent, selective partial agonist at the nociceptin/orphanin FQ peptide receptor in vitro. Three phase 1 studies were conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating single- and multiple-dose administration of sunobinop in healthy participants. Study 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study. Study 2 was a randomized, double-blind, placebo-controlled, multiple-ascending dose study. Study 3 was a randomized, open-label, single-dose, 4-way crossover study of oral and sublingual sunobinop comparing morning (AM) and bedtime (PM) administration. Seventy participants were included. Systemic exposure (peak plasma concentration [Cmax], area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration [AUC0-t], and area under the plasma concentration-time curve from time 0 extrapolated to infinity [AUCinf]) of sunobinop was characterized by dose proportionality from 0.6 to 2 mg and increased less than proportionally from 3 to 30 mg. The PKs of sunobinop were similar, regardless of AM or PM administration, for both the oral and sublingual formulations. The majority of absorbed sunobinop was excreted unchanged in the urine within 8 hours of dosing, thereby showing rapid elimination with no appreciable accumulation following 14 consecutive days of once-daily dosing and suggesting exclusive renal elimination. Most treatment-emergent adverse events (TEAEs) were mild in severity; 1 severe TEAE occurred and all TEAEs resolved by the end of the studies. Sunobinop was generally well-tolerated and safe across the range of doses evaluated and presents a clinical profile suitable for continued development.