Effects of a 12-week telehealth exercise intervention on gait speed and gait deviations in adults with Down syndrome.

BACKGROUND: Altered gait patterns and reduced walking speed are commonly reported in adults with Down syndrome (DS). Research on the effects of DS-specific exercise programmes on adults with DS is lacking. The purpose of this quasi-experimental study was to evaluate the changes in gait deviations and walking speed in adults with DS after a DS-specific exercise programme. METHODS: Twenty participants underwent a 12-week, DS-specific exercise programme in a telehealth format. Before and after the intervention, gait deviations were assessed with the Ranchos Los Amigos Observational Gait Analysis form, and comfortable walking speed was evaluated with the 4-m walk test. RESULTS: We observed increased comfortable walking speed and reduced gait deviations in the whole gait cycle in adults with DS after the intervention. There were fewer gait deviations during single-leg stance and swing-limb advancement and at the hip, knee and ankle joints after the 12-week exercise programme. CONCLUSIONS: Gait speed and observable gait impairments in adults with DS significantly improved following a 12-week telehealth exercise programme.

Effectiveness of Computerized Cognitive Training on Working Memory in Pediatric Cancer Survivors: A Systematic Review and Meta-analysis.

BACKGROUND: Interactive features of computerized cognitive training (CCT) may enhance adherence to training, providing a relatively low-cost intervention. A robust systematic review on the effectiveness of CCT for improving working memory (WM) among pediatric survivors with cancer is lacking. OBJECTIVE: To summarize the available evidence and determine the effectiveness of CCT for WM among pediatric survivors with cancer. INTERVENTIONS/METHODS: Five databases were searched. The Effective Public Health Practice Project was used to assess the study quality. ReviewerManager was used. The primary outcome was WM performance. Secondary outcomes included processing speed, attention, intervention adherence, and number of adverse events. RESULTS: Six studies were included. Regarding overall quality, 1 study was weak, and 5 studies were moderate. Five studies reported a significant improvement of WM postintervention (P < .05). The meta-analysis of Cogmed interventions on symbolic WM revealed a significant difference between groups (vs placebo), with an overall pooled effect size of 0.71 (95% confidence interval, 0.02-1.41; P = .04). Two and 4 studies investigated the effects of CCT on processing speed and attention, respectively, with conflicting results. Four studies reported adherence of 80% or greater. Two studies reported no adverse events. CONCLUSIONS: Computerized cognitive training using Cogmed has a significant positive effect on WM. The effects of CCT on processing speed and attention remain inconclusive. IMPLICATIONS FOR PRACTICE: More rigorous trials should be conducted to elucidate the cognitive effects of CCT, particularly processing speed and attention, in the pediatric population with cancer. Further studies should consider combining CCT with other existing interventions to strengthen their effectiveness.

Virtual urgent care is here to stay: driving toward safe, equitable, and sustainable integration within emergency medicine.

BACKGROUND: Virtual care in Canada rapidly expanded during the COVID-19 pandemic in a low-rules environment in response to pressing needs for ongoing access to care amid public health restrictions. Emergency medicine specialists now face the challenge of advising on which virtual urgent care services ought to remain as part of comprehensive emergency care. Consideration must be given to safe, quality, and appropriate care as well as issues of equitable access, public demand, and sustainability (financial and otherwise). The aim of this project was to summarize current literature and expert opinion and formulate recommendations on the path forward for virtual care in emergency medicine. METHODS: We formed a working group of emergency medicine physicians from across Canada working in a variety of practice settings. The virtual care working group conducted a scoping review of the literature and met monthly to discuss themes and develop recommendations. The final recommendations were circulated to stakeholders for input and subsequently presented at the 2023 Canadian Association of Emergency Physicians (CAEP) Academic Symposium for discussion, feedback, and refinement. RESULTS: The working group developed and reached unanimity on nine recommendations addressing the themes of system design, equity and accessibility, quality and patient safety, education and curriculum, financial models, and sustainability of virtual urgent care services in Canada. CONCLUSION: Virtual urgent care has become an established service in the Canadian health care system. Emergency medicine specialists are uniquely suited to provide leadership and guidance on the optimal delivery of these services to enhance and complement emergency care in Canada.

RéSUMé: CONTEXTE: Les soins virtuels au Canada ont rapidement pris de l'ampleur pendant la pandémie de COVID-19 dans un environnement où les règles sont peu strictes, en réponse aux besoins urgents d'accès continu aux soins dans un contexte de restrictions en santé publique. Les spécialistes de la médecine d'urgence sont maintenant confrontés au défi de conseiller sur les services de soins d'urgence virtuels qui devraient rester dans le cadre des soins d'urgence complets. Il faut tenir compte des soins sécuritaires, de qualité et appropriés, ainsi que des questions d'accès équitable, de la demande publique et de la durabilité (financière et autre). L'objectif de ce projet était de résumer la littérature actuelle et l'opinion d'experts et de formuler des recommandations sur la voie à suivre pour les soins virtuels en médecine d'urgence. MéTHODES: Nous avons formé un groupe de travail composé de médecins urgentistes de partout au Canada qui travaillent dans divers milieux de pratique. Le groupe de travail sur les soins virtuels a effectué un examen de la portée de la documentation et s'est réuni chaque mois pour discuter des thèmes et formuler des recommandations. Les recommandations finales ont été distribuées aux intervenants pour obtenir leurs commentaires, puis présentées au symposium universitaire 2023 de l'Association canadienne des médecins d'urgence (ACMU) pour discussion, rétroaction et perfectionnement. RéSULTATS: Le groupe de travail a élaboré et atteint l'unanimité sur neuf recommandations portant sur les thèmes de la conception du système, de l'équité et de l'accessibilité, de la qualité et de la sécurité des patients, de l'éducation et des programmes, des modèles financiers et de la viabilité des services virtuels de soins d'urgence au Canada. CONCLUSION : Les soins d'urgence virtuels sont devenus un service établi dans le système de santé canadien. Les spécialistes en médecine d'urgence sont particulièrement bien placés pour fournir un leadership et des conseils sur la prestation optimale de ces services afin d'améliorer et de compléter les soins d'urgence au Canada.

Characterization of chemical components of fresh and aged aerosol from vehicle exhaust emissions in Hong Kong.

The chemical properties of fresh and aged aerosol emitted during controlled vehicular exhaust emissions were characterized in the analysis. Pyrene (10417.1 ± 534.9 ng kg-1) is the most abundant of all analyzed compounds in total fresh emission and succinic acid (57359.8 ± 4000.3 ng kg-1) is for the total aged emission. The fresh emission factors (EFfresh) of all compounds in the n-alkanes group demonstrate higher average emissions for the two vehicles with EURO 3 standard compared to the other vehicles. The EFfresh for benzo [a]pyrene is in descending order: G1 (183.1 ± 144.7 ng kg-1) > G3 (103.4 ± 60.1 ng kg-1) > G4 (91.2 ± 80.1 ng kg-1) > G2 (88.6 ± 93.9 ng kg-1). Aged/fresh (A/F) emission ratios (>20) confirmed that these diacid compounds are generated by the photooxidation of primary pollutants that emitted from gasoline combustions. High A/F ratios (>200) in phthalic acid, isophthalic acid and terephthalic acid under idling mode imply relatively more intense photochemical reactions for their productions compared with other chemical groups. Strong positive correlations (r > 0.6) were observed between the degradation of toluene and formations of pinonic acid, succinic acid, adipic acid, terephthalic acid, glutaric acid and citramalic acid after the aging process, suggesting possible photooxidation of toluene that can lead to secondary organic aerosol (SOA) formation in the urban atmosphere. The findings demonstrate that vehicle emission standards for pollution in relation to the change of particulate matter chemical compositions and SOA formations. The results warrant a need for regulated reformulation for such vehicles.

Robust Ellipse Fitting Based on Maximum Correntropy Criterion With Variable Center.

The presence of radically irregular data points (RIDPs), which are referred to as the subset of measurements that represents no or little information, can significantly degrade the performance of ellipse fitting methods. We develop an ellipse fitting method that is robust to RIDPs based on the maximum correntropy criterion with variable center (MCC-VC), where an adaptable Laplacian kernel is used. For single ellipse fitting, we formulate a non-convex optimization problem and divide it into two subproblems, one to estimate the kernel bandwidth and the other the kernel center. We design sufficiently accurate convex approximation to each subproblem that will lead to computationally efficient closed-form solutions. The two subproblems are solved in an alternate manner until convergence is reached. We also investigate coupled ellipses fitting. While there exist multiple ellipses fitting methods in the literature, we develop a coupled ellipses fitting method by exploiting the underlying special structure, where the associations between the data points and ellipses are absent in the problem. The proposed method first introduces an association vector for each data point and then formulates a non-convex mixed-integer optimization problem to establish the data associations, which is approximately solved by relaxing it into a second-order cone program. Using the estimated data associations, we then extend the proposed single ellipse fitting method to accomplish the final coupled ellipses fitting. The proposed method is shown to perform significantly better than the existing methods using both simulated data and real images.

Approaches to characterizing oscillatory burst detection algorithms for electrophysiological recordings.

BACKGROUND: Cognitive processes are associated with fast oscillations of the local field potential and electroencephalogram. There is a growing interest in targeting them because these are disrupted by aging and disease. This has proven challenging because they often occur as short-lasting bursts. Moreover, they are obscured by broad-band aperiodic activity reflecting other neural processes. These attributes have made it exceedingly difficult to develop analytical tools for estimating the reliability of detection methods. NEW METHOD: To address this challenge, we developed an open-source toolkit with four processing steps, that can be tailored to specific brain states and individuals. First, the power spectrum is decomposed into periodic and aperiodic components, each of whose properties are estimated. Second, the properties of the transient oscillatory bursts that contribute to the periodic component are derived and optimized to account for contamination from the aperiodic component. Third, using the burst properties and aperiodic power spectrum, surrogate neural signals are synthesized that match the observed signal's spectrotemporal properties. Lastly, oscillatory burst detection algorithms run on the surrogate signals are subjected to a receiver operating characteristic analysis, providing insight into their performance. RESULTS: The characterization algorithm extracted features of oscillatory bursts across multiple frequency bands and brain regions, allowing for recording-specific evaluation of detection performance. For our dataset, the optimal detection threshold for gamma bursts was found to be lower than the one commonly used. COMPARISON WITH EXISTING METHODS: Existing methods characterize the power spectrum, while ours evaluates the detection of oscillatory bursts. CONCLUSIONS: This pipeline facilitates the evaluation of thresholds for detection algorithms from individual recordings.

Effectiveness of using high-fidelity simulation on learning outcomes in undergraduate nursing education: systematic review and meta-analysis.

OBJECTIVE: High-fidelity simulation-based learning, which mimics situation, environmental, and psychological exposure in the clinical setting, potentially helps nursing students acquire knowledge, confidence, and skills in learning clinical skills during the transition from pre-clinical to clinical practice. However, inconsistent evidence on its effect on learning outcomes was presented across the studies. The aim of our study was to review and analyze the effectiveness of high-fidelity simulation on learning outcomes in undergraduate nursing education. MATERIALS AND METHODS: This study was a systematic review and meta-analysis of experimental studies. A literature search was conducted in four databases (CINAHL, SocINDEX, PubMed, and Web of Science) until July 2021. The Cochrane Risk of Bias Tool was used to appraise the studies' quality. The random-effect model was used to conduct a meta-analysis. RESULTS: Fourteen studies were eligible for quantitative synthesis. The pooled effect indicated high-fidelity simulation-based learning significantly increased nursing students' knowledge acquisition (standardized mean difference [SMD]: 1.73, p < 0.001), self-confidence (SMD: 0.56, p= 0.019) and skills performance (SMD: 1.71, p= 0.006). CONCLUSIONS: Stakeholders within the academic institution may consider enculturating the involvement of high-fidelity simulation as part of an innovative teaching strategy in nursing curricula. Therefore, when graduates enter the workforce, they can function quickly and practice confidently in clinical settings without bringing potential harm.

Evaluation of a group-based sensorimotor intervention programme to improve Chinese handwriting of primary school students.

Objective: Sensorimotor performance is influential in Chinese handwriting, but few studies have examined the efficacy of sensorimotor-based interventions on Chinese handwriting among primary school students with poor handwriting performance. The study aims to evaluate a sensorimotor-based intervention to improve handwriting in the mainstream primary schools. Methods: This study adopted a two-group pretest-posttest design. An 8-session group-based sensorimotor intervention was delivered to school-aged children (mean age = 8.1, 68% male). Group A had 2 sessions every week, while Group B had 4 sessions every week. Analysis of variance with repeated measures was used to test the effects. Results: The intervention had a significant time effect (p < .05) in terms of improving handwriting process (d = 0.33-1.10), manual dexterity (d = 0.57), visual memory (d = 0.70), visual-spatial perception (d = 0.37), and motor and postural skills (d = 0.73). The effect sizes ranged from medium to large. For the handwriting process, time per character had a significant group × time interaction, with post hoc analysis showing that Group A had a significantly large effect (d = 1.89, p < .001) while Group B did not. Conclusions: The group-based sensorimotor intervention programme appeared to show improvements in students with fair skills in writing Chinese characters. It appears that the effect is better if the training sessions are spaced out in one month rather than intensively conducted within two weeks. It might be related to more involvement from parents, and students need more time for practice after the training sessions.

Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5-a]pyrimidine CFTR Activator That Ameliorates Dry Eye Disease.

Dry eye disease (DED) is one of the most prevalent ocular diseases but has limited treatment options. Cystic fibrosis transmembrane conductance regulator (CFTR), a major chloride channel that stimulates fluid secretion in the ocular surface, may pave the way for new therapeutic strategies for DED. Herein, we report the optimization of Cact-3, a potent CFTR activator with poor solubility, to 16d, a potent CFTR activator with suitable solubility for eye drop formulation. Notably, 16d was well distributed in target tissues including cornea and conjunctiva with minimal systemic exposure in rabbit. Topical ocular instillation of 16d significantly enhanced tear secretion and improved corneal erosion in a mouse model of DED. In addition, 16d significantly reduced mRNA expression of pro-inflammatory cytokines including IL-1ß, IL-17, and TNF-α and MMP2 in cornea and conjunctiva of DED mice.

Structures and localized vibrational states of defects in graphite by tight-binding calculations.

The structural and vibrational properties of pristine graphite and point defects in graphite are studied by tight-binding (TB) calculations using a three-center TB potential model. We showed that the three-center TB potential without "ad hoc" van der Waals interaction corrections can accurately describe the inter-layer distance of graphite and the lowest-energy structures and stabilities of typical point defects in graphite. The results from our TB calculations are in good agreement with those from density-functional theory calculations with van der Waals interaction corrections. We also investigated the vibrational properties to gain better understanding on the localization of vibrational states induced by the point defects. Our calculation results show that although localized or quasi-localized vibrational modes can be found in all defected graphite, the localization induced by Frenkel pair, dual-vacancy, and dual-interstitial defects is much stronger. Atomic displacements associated with the localized vibrational modes induced by these three point defects are also analyzed.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

Novel CFTR Activator Cact-3 Ameliorates Ocular Surface Dysfunctions in Scopolamine-Induced Dry Eye Mice.

Cystic fibrosis transmembrane conductance regulator (CFTR) is highly expressed on the ocular epithelium and plays a pivotal role in the fluid secretion driven by chloride transport. Dry eye disease is one of the most common diseases with limited therapeutic options. In this study, a high-throughput screening was performed to identify novel CFTR activators capable of inducing chloride secretion on the ocular surface. The screening of 50,000 small molecules revealed three novel CFTR activators. Among them, the most potent CFTR activator, Cact-3 (7-(3,4-dimethoxyphenyl)-N-(4-ethoxyphenyl)pyrazolo [1,5-α]pyrimidine-2-carboxamide), produced large and sustained Cl- currents in WT-CFTR-expressing FRT cells with no alterations of ANO1 and hERG channel activity. The application of Cact-3 strongly activated CFTR in the ocular epithelia of mice and it also significantly increased CFTR-mediated Cl- transport in a primary cultured human conjunctival epithelium. Cact-3 strongly stimulated tear secretion in normal mice. In addition, Cact-3 significantly reduced ocular surface damage and the expression of proinflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in an experimental mouse model of dry eye disease. These results suggest that Cact-3, a novel CFTR activator, may be a potential development candidate for the treatment of dry eye disease.

Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of ß-catenin.

Vestibular schwannoma (VS), one of characteristic tumors of neurofibromatosis type 2 (NF2), is an intracranial tumor that arises from Schwann cells of the vestibular nerve. VS results in hearing loss, tinnitus, dizziness, and even death, but there are currently no FDA-approved drugs for treatment. In this study, we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells. Among 1019 natural products from the Korea Chemical Bank screened, we found that celastrol, a pentacyclic triterpene derived from a Tripterygium Wilfordi plant, exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5 µM. Celastrol (0.5, 1 µM) dose-dependently inhibited the proliferation of primary VS cells derived from VS patients. Celastrol also inhibited the growth, and induced apoptosis of two other VS cell lines (HEI-193 and SC4). Aberrant activation of Wnt/ß-catenin signaling has been found in VS isolated from clinically defined NF2 patients. In HEI-193 and SC4 cells, we demonstrated that celastrol (0.1, 0.5 µM) dose-dependently inhibited TOPFlash reporter activity and protein expression of ß-catenin, but not mRNA level of ß-catenin. Furthermore, celastrol accelerated the degradation of ß-catenin by promoting the formation of the ß-catenin destruction complex. In nude mice bearing VS cell line SC4 allografts, administration of celastrol (1.25 mg · kg-1 · d-1, i.p. once every 3 days for 2 weeks) significantly suppressed the tumor growth without showing toxicity. Collectively, this study demonstrates that celastrol can inhibit Wnt/ß-catenin signaling by promoting the degradation of ß-catenin, consequently inhibiting the growth of VS.

Utilization of the Youth Quitline as an opportunity for an undergraduate nursing students to deliver smoking cessation counseling as their clinical placement: An implementation of a service-learning model.

BACKGROUND: Smoking is an important modifiable risk factor of morbidities and mortality. Although healthcare professionals play an important role in smoking cessation, their adoption of such practices is relatively low because of inadequate training. To address this issue, we incorporated a service-learning model to operate the Youth Quitline. Undergraduate nursing students were trained and received supervision while delivering smoking cessation counseling through the Youth Quitline as their clinical placement. OBJECTIVES: We evaluated the effectiveness of the placement by assessing students' knowledge, attitudes and practices regarding smoking cessation and tobacco control. DESIGN: One-group pretest-posttest design. SETTING: Youth Quitline. PARTICIPANTS: A total of 61 third-year students in a mental health nursing program. METHODS: Students were required to complete 80 h at the Youth Quitline. The 80 h were divided into 20 sessions; students used four sessions to approach and recruit youth smokers in the community, then provided them with telephone counseling for the rest of the time. Prior to the placement, students attended a 2-day workshop. The outcomes were changes in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control 3 months after the placement compared with baseline. RESULTS: From January-June 2021, students conducted 105 outreach activities to identify 3142 smokers in the community, and provided telephone counseling for 336 smokers via Youth Quitline. Compared with baseline, significant improvements were observed in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control at 3-month follow-up. CONCLUSIONS: The clinical placement improved students' knowledge, attitudes and practices regarding smoking cessation and tobacco control, enhancing their competency in providing support to assist smokers to quit in their future practice. Incorporating the service-learning model in existing community-based services can provide additional venues for nursing students to practice. This is particularly important because many venues have restricted access during the COVID-19 pandemic.

Sleep disruption and its contributing factors in Chinese survivors of childhood cancer: A cross-sectional study.

OBJECTIVES: This study provided information about sleep disruption, particularly its prevalence and severity among Hong Kong Chinese childhood cancer survivors. Additionally, we identified the factors influencing sleep disruption and explored how fatigue, depressive symptoms and physical activity (PA) affect sleep disruption. METHODS: Four hundred two survivors 6-18 years old and 50 age- and gender-matched healthy counterparts were assessed for depressive symptoms, fatigue, PA and subjective sleep quality. Demographic and clinical information were collected. Multiple logistic regression analyses were conducted to identify any factors contributing to poor sleep. RESULTS: Mean scores of depressive symptoms, fatigue for children and that for adolescents, and PA in survivors were 16.1 (SD = 11.1), 24.6 (SD = 10.3), 27.7 (SD = 7.8), and 3.08 (SD = 2.9), respectively. 44.8% of the survivors were poor sleepers, which was more that in healthy counterparts. The three most common sleep problem were prolonged sleep latency (31.9%), daytime dysfunction (23.4%), and sleep disturbance (22.9%). The time since last treatment (children: AOR = 0.54, 95% CI = 0.30-0.96, p = 0.04; adolescents: AOR = 0.80, 95% CI = 0.70-0.92, p < 0.01) and PA levels (children: AOR = 0.46, 95% CI = 0.260-0.82, p = 0.01; adolescents: AOR = 0.70, 95% CI = 0.49-0.98, p = 0.04) were negatively associated with sleep disruption, while depressive symptoms (children: AOR = 1.31, 95% CI = 1.04-1.64, p = 0.02; adolescents: AOR = 1.07, 95% CI = 1.01-1.13, p = 0.03), fatigue (children: AOR = 1.15, 95% CI = 1.00-1.31, p = 0.04; adolescents: AOR = 1.08, 95% CI = 1.02-1.15, p = 0.01), number of treatment received (children: AOR = 16.56, 95% CI = 1.27-216.82, p = 0.03; adolescents: AOR = 7.30, 95% CI = 2.36-22.56, p < 0.01), and co-sleeping (children: AOR = 29.19, 95% CI = 1.65-511.57, p = 0.02; adolescents: AOR = 4.63, 95% CI = 1.22-17.61, p = 0.02) were positively associated with sleep disruption. CONCLUSION: Physical activity made the largest contribution to reduce sleep disruption. It is crucial to advocate for the adoption and maintenance of PA in survivorship.