Movement Guidelines for Young Children: Engaging Stakeholders to Design Dissemination Strategies in the Hong Kong Early Childhood Education Context

Background Early childhood is a critical period during which patterns of movement behaviors are formed. The World Health Organization had endorsed guidelines for physical activity, sedentary behavior and sleep over a 24-h time period, which had been adopted by the Center for Health Protection of Hong Kong. This paper reports on stakeholder engagements that were conducted to inform the design of strategies to disseminate the guidelines in early childhood education (ECE) settings. Methods Using a mixed-methods study design, we sought to (a) assess the stakeholders\u27 levels of awareness and knowledge of the Hong Kong movement guidelines for young children and (b) identify the factors that influence the uptake of the said guidelines. We conducted an online survey of early childhood education teachers (N =314), twelve focus groups involving teachers (N = 18) and parents (N = 18), and individual interviews of key informants (N = 7) and domestic workers who provide care for preschool-aged children (N = 7). Descriptive statistics were used for the quantitative data, and thematic analysis was performed on the qualitative data using an inductive and semantic approach following a realist framework. Findings Our findings show that teachers were aware of the movement guidelines for young children, but their knowledge of the specific guidelines was deficient; parents and domestic workers had limited awareness and knowledge of the guidelines. Uptake of the movement guidelines is enabled by parent engagement, activities in the ECE centers, home-school cooperation, and community activities for children. The challenges include the time poverty of parents, local curriculum requirements, limited physical spaces, social values, and pandemic-related restrictions. Conclusion We recommend that dissemination strategies in the ECE context should deliver knowledge content and support stakeholders in mitigating the challenges associated with time, space, and social conditions

Evaluation of a School-Based Dissemination of the Movement Guidelines for Young Children in Hong Kong: Study Protocol

Background Healthy movement behaviors in early childhood are believed to track to adulthood, potentially imparting protective benefits against non-communicable diseases. Highlighting the collaborative and complementary roles of parents and educators in promoting health of young children, this study aims to enable parents and teachers to successfully promote healthy movement behaviors in young children. Guidelines for physical activity, sedentary screen time, and sleep of children aged 2 to 6 years will be systematically disseminated to parents and teachers of children enrolled in early childhood education centers (ECECs) in Hong Kong. An evaluation will be conducted to assess the implementation process and the outcomes of the dissemination of said guidelines. Methods The evaluation will include formative and summative components to examine the implementation (i.e., process evaluation) and the outcomes (i.e., outcome evaluation). Participants include teachers, parents, and children from ECECs in Hong Kong. The process evaluation will be guided by the RE-AIM framework (i.e., reach, efficacy, adaptation, implementation, maintenance). Data gathering and analysis will take a mixed-methods triangulation design - convergence model. The outcome evaluation consists of a non-randomized observational study, using quantitative data from questionnaires and accelerometers. The primary outcome to be measured is the extent to which children meet the guidelines for physical activity, sedentary screen time, and sleep; the secondary outcome is teachers’ and parents’ knowledge and awareness of the guidelines. Discussion Young children who engage in healthy movement behaviors are likely to become adults who will have the disposition to engage in behaviors that have protective effects against non-communicable diseases. The findings of this evaluation are expected to contribute to improving the strategies of systems and government agencies that aspire to promote healthy movement behaviors of young children

When Small Words Foretell Academic Success: The Case of College Admissions Essays

Abstract The smallest and most commonly used words in English are pronouns, articles, and other function words. Almost invisible to the reader or writer, function words can reveal ways people think and approach topics. A computerized text analysis of over 50,000 college admissions essays from more than 25,000 entering students found a coherent dimension of language use based on eight standard function word categories. The dimension, which reflected the degree students used categorical versus dynamic language, was analyzed to track college grades over students' four years of college. Higher grades were associated with greater article and preposition use, indicating categorical language (i.e., references to complexly organized objects and concepts). Lower grades were associated with greater use of auxiliary verbs, pronouns, adverbs, conjunctions, and negations, indicating more dynamic language (i.e., personal narratives). The links between the categorical-dynamic index (CDI) and academic performance hint at the cognitive styles rewarded by higher education institutions

Effects of Levodopa-Carbidopa Intestinal Gel Compared with Optimized Medical Treatment on Nonmotor Symptoms in Advanced Parkinson’s Disease: INSIGHTS Study

Background. Nonmotor symptoms (NMS) are common in advanced Parkinson's disease (APD) and reduce health-related quality of life. Objective. The aim of the study was to evaluate levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) on NMS in APD. Methods. INSIGHTS was a phase 3b, open-label, randomized, multicenter study in patients with APD (LCIG or OMT, 26 weeks) (NCT02549092). Primary outcomes assessed were total NMS (NMS scale (NMSS) and PD sleep scale (PDSS-2)). Key secondary outcomes included the Unified PD Rating Scale (UPDRS) Part II, Clinical Global Impression of Change (CGI-C), and PD Questionnaire-8 (PDQ-8). Additional secondary measures of Patient Global Impression of Change (PGIC), King's PD Pain Scale (KPPS), and Parkinson Anxiety Scale (PAS) also were evaluated. Finally, safety was assessed. Results. Out of 89 patients randomized, 87 were included in the analysis (LCIG, n = 43; OMT, n = 44). There were no significant differences in NMSS or PDSS-2 total score changes (baseline to Week 26) between LCIG and OMT; within-group changes were significant for NMSS (LCIG, p < 0.001; OMT, p=0.005) and PDSS-2 (LCIG, p < 0.001; OMT, p < 0.001). Between-group treatment differences were nominally significant for UPDRS Part II (p=0.006) and CGI-C (p < 0.001) at Week 26 in favor of LCIG; however, statistical significance could not be claimed in light of primary efficacy outcomes. PGIC (Week 26) and KPPS (Week 12) scores were nominally significantly reduced with LCIG versus OMT (p < 0.001; p < 0.05). There were no significant differences in PDQ-8 or PAS. Adverse events (AEs) were mostly mild to moderate; common serious AEs were pneumoperitoneum (n = 2) and stoma-site infection (n = 2) (LCIG). Conclusions. There were no significant differences between LCIG versus OMT in NMSS or PDSS-2; both LCIG and OMT groups significantly improved from baseline. AEs were consistent with the known safety profile

Patient Empowerment Programme (PEP) in Primary Care Reduced All-cause Mortality and Cardiovascular Diseases in Patients with Type 2 Diabetes Mellitus: A Population-based Propensity Matched Cohort Study

Running title: PEP reduced death and CVD events Clinical trial number and registry: NCT01935349, ClinicalTrials.gov PEP DM CVD Manuscript 20140917 Page 1 of 15 patients treated at primary care outpatient clinics through community trained professional educators. Non-PEP participants were matched one-to-one with the PEP participants using propensity score method with respect to their baseline covariates. Cox proportional hazard regressions were performed to estimate the associations of PEP with the occurrence of first CVD event, coronary heart disease, stroke, heart failure and death from any cause, controlling for baseline characteristics. Conclusions: Enrolment in PEP was associated with reduced all-cause mortality and first CVD events among T2DM patients. The CVD benefit of PEP might be attributable to improving metabolic control through empowerment of self-care and enhancement of quality of diabetes care in primary care. Word Count: 25

Carvedilol blocks neural regulation of breast cancer progression in vivo and is associated with reduced breast cancer mortality in patients

© 2021 Elsevier Ltd Purpose: The sympathetic nervous system drives breast cancer progression through β-adrenergic receptor signalling. This discovery has led to the consideration of cardiac β-blocker drugs as novel strategies for anticancer therapies. Carvedilol is a β-blocker used in the management of cardiovascular disorders, anxiety, migraine and chemotherapy-induced cardiotoxicity. However, little is known about how carvedilol affects cancer-related outcomes. Methods: To address this, we investigated the effects of carvedilol on breast cancer cell lines, in mouse models of breast cancer and in a large cohort of patients with breast cancer (n = 4014). Results: Treatment with carvedilol blocked the effects of sympathetic nervous system activation, reducing primary tumour growth and metastasis in a mouse model of breast cancer and preventing invasion by breast cancer cell lines. A retrospective analysis found that women using carvedilol at breast cancer diagnosis (n = 136) had reduced breast cancer-specific mortality compared with women who did not (n = 3878) (5-year cumulative incidence of breast cancer deaths: 3.1% versus 5.7%; p = 0.024 and 0.076 from univariate and multivariable analyses, respectively) after a median follow-up of 5.5 years. Conclusions: These findings provide a rationale to further explore the use of the β-blocker carvedilol as a novel strategy to slow cancer progression

Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment

SJS/TEN 2019: From science to translation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Effects of Subthalamic Nucleus Lesions and Stimulation upon Corticostriatal Afferents in the 6-Hydroxydopamine-Lesioned Rat

Abnormalities of striatal glutamate neurotransmission may play a role in the pathophysiology of Parkinson's disease and may respond to neurosurgical interventions, specifically stimulation or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate. Corticostriatal terminals can be distinguished within the striatum at the electron microscopic level as their synaptic vesicles contain the vesicular glutamate transporter, VGLUT1. The majority of terminals which are immunolabeled for glutamate but are not VGLUT1 positive are likely to be thalamostriatal afferents. We compared the effects of short term, high frequency, STN stimulation and lesioning in 6-hydroxydopamine (6OHDA)-lesioned rats upon striatal terminals immunolabeled for both presynaptic glutamate and VGLUT1. 6OHDA lesions resulted in a small but significant increase in the proportions of VGLUT1-labeled terminals making synapses on dendritic shafts rather than spines. STN stimulation for one hour, but not STN lesions, increased the proportion of synapses upon spines. The density of presynaptic glutamate immuno-gold labeling was unchanged in both VGLUT1-labeled and -unlabeled terminals in 6OHDA-lesioned rats compared to controls. Rats with 6OHDA lesions+STN stimulation showed a decrease in nerve terminal glutamate immuno-gold labeling in both VGLUT1-labeled and -unlabeled terminals. STN lesions resulted in a significant decrease in the density of presynaptic immuno-gold-labeled glutamate only in VGLUT1-labeled terminals. STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission

HER-2 overexpression differentially alters transforming growth factor-β responses in luminal versus mesenchymal human breast cancer cells

INTRODUCTION: Amplification of the HER-2 receptor tyrosine kinase has been implicated in the pathogenesis and aggressive behavior of approximately 25% of invasive human breast cancers. Clinical and experimental evidence suggest that aberrant HER-2 signaling contributes to tumor initiation and disease progression. Transforming growth factor beta (TGF-β) is the dominant factor opposing growth stimulatory factors and early oncogene activation in many tissues, including the mammary gland. Thus, to better understand the mechanisms by which HER-2 overexpression promotes the early stages of breast cancer, we directly assayed the cellular and molecular effects of TGF-β1 on breast cancer cells in the presence or absence of overexpressed HER-2. METHODS: Cell proliferation assays were used to determine the effect of TGF-β on the growth of breast cancer cells with normal or high level expression of HER-2. Affymetrix microarrays combined with Northern and western blot analysis were used to monitor the transcriptional responses to exogenous TGF-β1 in luminal and mesenchymal-like breast cancer cells. The activity of the core TGF-β signaling pathway was assessed using TGF-β1 binding assays, phospho-specific Smad antibodies, immunofluorescent staining of Smad and Smad DNA binding assays. RESULTS: We demonstrate that cells engineered to over-express HER-2 are resistant to the anti-proliferative effect of TGF-β1. HER-2 overexpression profoundly diminishes the transcriptional responses induced by TGF-β in the luminal MCF-7 breast cancer cell line and prevents target gene induction by a novel mechanism that does not involve the abrogation of Smad nuclear accumulation, DNA binding or changes in c-myc repression. Conversely, HER-2 overexpression in the context of the mesenchymal MDA-MB-231 breast cell line potentiated the TGF-β induced pro-invasive and pro-metastatic gene signature. CONCLUSION: HER-2 overexpression promotes the growth and malignancy of mammary epithelial cells, in part, by conferring resistance to the growth inhibitory effects of TGF-β. In contrast, HER-2 and TGF-β signaling pathways can cooperate to promote especially aggressive disease behavior in the context of a highly invasive breast tumor model