Development and validation of a health literacy scale for family caregivers of older people with chronic illness.

BACKGROUND: Family caregivers (FCs) encounter a variety of health problems in older people with chronic illness, necessitating a certain level of health literacy to access, understand, appraise and apply health information and services. This study aimed to develop and validate a scale for measuring health literacy among FCs of older people with chronic illness. METHODS: Concept mapping was first employed to develop a conceptual model of health literacy of FCs. Scale domains were derived from the conceptual model, and item generation was performed using deductive and inductive methods. Quantitative methods, including merging scale dimensions and items, expert reviews, cognitive interviews, and item reduction analysis, were used to refine the scale. Confirmatory factor analysis was employed to validate the scale's structure. Concurrent validity, internal consistency, and test-retest reliability were also examined. RESULTS: A 20-dimension conceptual model was developed, and 60 items were generated for the scale. Expert review (content validity index > 0.85) and cognitive interview with FCs confirmed the relevance and clarity of the majority of the generated scale items. Confirmatory factor analysis with 451 FCs of older people with chronic illness supported a 5-factor structure (symptom management, daily personal care and household tasks, care coordination, communication and relationship with the care recipient, and self-care of caregivers) with 42 finalized scale items, including four levels of health literacy skills (accessing, understanding, appraising and applying health information). Concurrent validity with the European Health Literacy Questionnaire (HLS-EU-Q47) was satisfactory (r = 0.67, p < 0.01). The Cronbach's α coefficient of the scale was 0.96, with subscales ranging from 0.84 to 0.91. The two-week test-retest reliability was 0.77 (p < 0.01). CONCLUSION: This study developed a conceptual model explaining the concept and factors of health literacy among FCs of older people with chronic illness that could provide the groundwork for future studies in developing relevant evidence-based interventions. A new Health Literacy Scale-Family Caregiver (HLS-FC) with satisfactory psychometric properties was developed in this study, which can be utilized to identify caregivers with insufficient health literacy and facilitate timely interventions by healthcare professionals.

Developing a storybook package for bereaved siblings: a pilot study of the effectiveness for enhancing the perceived knowledge and confidence of health and social care professionals in Hong Kong.

A pilot randomized controlled trial was conducted to examine the effectiveness of a storybook package for enhancing the perceived knowledge and confidence of health and social care professionals in working with bereaved child siblings and their parents before and after the loss. Open-ended questions were asked to collect feedback, and thematic analyses were conducted to generate the themes. Quantitative findings provided preliminary but not strong evidence of its effectiveness, but qualitative findings showed that participants perceived their knowledge about supporting bereaved siblings and their parents was enhanced and considered the storybook package a useful tool for facilitating their practice. Participants also reflected on how real and specific the stories in the storybook should be. This study is the first step in developing an evidence-based practice tool for health and social care professionals. Future studies are required to further examine its effectiveness for practice.

Cross-Cultural Adaptation and Psychometric Properties of the Chinese Version of the Knee Osteoarthritis Fears and Beliefs Questionnaire.

This study aimed to adapt and validate the Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ) for Chinese patients, thereby advancing the understanding of fear-avoidance behaviors. Adopting a cross-sectional design, data were collected for 241 subjects (78.8% women; mean age 68.0 ± 7.8 years) across various healthcare settings in Hong Kong. Exploratory factor analysis resulted in an 11-item questionnaire with three distinct subscales, covering fears and beliefs related to physicians and disease (six items), daily living activities (three items), and sports and leisure activities (two items). The overall Cronbach's α coefficient was 0.86, indicating strong internal consistency. The questionnaire exhibited favorable convergent validity. Confirmatory factor analyses confirmed a good model fit. Test-retest reliability analysis indicated a high intraclass correlation coefficient of 0.93 (95% confidence interval: 0.88, 0.96), and a Bland-Altman plot revealed a slight bias in two measurements (0.97 [0.19]) without a systematic trend. The adapted Chinese version of the KOFBeQ demonstrated robust psychometric properties in terms of validity and reliability, providing an effective tool for surveying Chinese patients with knee osteoarthritis. These findings offer valuable insights for clinicians and patients, aiding in informed decision-making and improved rehabilitation strategies.

Effects of a Family Caregiver-Delivered MultiSensory Cognitive Stimulation Intervention for Older People With Dementia During Coronavirus 2019: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Many community dementia services such as home-visiting services and center-based activities were suspended during the coronavirus 2019 pandemic. This study investigated the efficacy of a caregiver-delivered cognitive stimulation therapy (CDCST) on people with dementia during the pandemic. RESEARCH DESIGN AND METHODS: This was a 2-arm randomized controlled trial involving 241 patient-caregiver dyads assigned to a 15-week CDCST or control group (usual care). We hypothesized that CDCST would facilitate significant improvements among people with dementia (cognition, behavioral/psychiatric symptoms, and quality of life) and their caregivers (caregiving appraisal, attitudes, and psychological well-being) at postintervention (T1) and at the 12-week follow-up (T2). Generalized estimating equations evaluated the study outcomes. RESULTS: A total of 230 dyads completed the study, with good program adherence (93%). Participants in the CDCST showed significant improvements in cognition (p < .001), behavioral and psychiatric symptoms (p =. 027), and quality of life (p =.001) at the 3-month follow-up period. Family caregivers had improved positive aspects of caregiving (p = .008; p = .049) and decreased negative attitudes toward people with dementia (p =. 013; p < .001) at both T1 and T2. There were nonsignificant changes in the caregivers' perceived burden, distress, and psychological well-being. DISCUSSION AND IMPLICATIONS: Family caregivers could be trained to provide cognitive stimulation at home for people with dementia, which could benefit both parties. CDCST could manage to improve the cognition, neuropsychiatric symptoms, and quality of life of people with dementia, while also improving caregiving appraisal and negative attitudes among family caregivers. CLINICAL TRIAL REGISTRATION NUMBER: NCT03803592.

Prevalence of and factors associated with demoralization among family caregivers of palliative care patients in Hong Kong.

OBJECTIVES: This study aims to examine (1) the prevalence of demoralization among family caregivers of palliative care patients (PCP) in Hong Kong, (2) the percentage of caregivers who are demoralized but not depressed, (3) the factors associated with demoralization, and (4) the differences in caregivers' support needs between high and low levels of demoralization groups. METHODS: Ninety-four family caregivers were recruited and completed a questionnaire that included measures of demoralization, depression and caregiving strain, caregivers' support needs, and demographic information. RESULTS: The prevalence of demoralization among family caregivers of PCP was found to be 12.8% (cutoff score = 50) and 51.1% (cutoff score = 30). Although 27.7% of caregivers met the criteria of depression and demoralization, 12.8% of demoralized caregivers were not depressed. Depression and caregiving strain were identified as the predictors of demoralization. Caregivers with a poorer subjective physical status and a lower education level are more prone to demoralization. The three major caregivers' needs for support reported were (1) knowing what to expect in the future (77.7%); (2) knowing who to contact (74.5%); and (3) understanding your relative's illness (73.4%). Those who experienced a high level of demoralization often reported more need for support in end-of-life caregiving. SIGNIFICANCE OF RESULTS: This is the first study that focused on the demoralization of family caregivers of PCP in the East Asian context. Demoralization is prevalent among these caregivers. We recommend that early assessment of demoralization among family caregivers of PCP be considered, especially for those who are more depressed and have a higher level of caregiving stress.

Physical Activity Interventions to Alleviate Depressive Symptoms in Children and Adolescents: A Systematic Review and Meta-analysis.

Importance: Depression is the second most prevalent mental disorder among children and adolescents, yet only a small proportion seek or receive disorder-specific treatment. Physical activity interventions hold promise as an alternative or adjunctive approach to clinical treatment for depression. Objective: To determine the association of physical activity interventions with depressive symptoms in children and adolescents. Data Sources: PubMed, CINAHL, PsycINFO, EMBASE, and SPORTDiscus were searched from inception to February 2022 for relevant studies written in English, Chinese, or Italian. Study Selection: Two independent researchers selected studies that assessed the effects of physical activity interventions on depressive symptoms in children and adolescents compared with a control condition. Data Extraction and Synthesis: A random-effects meta-analysis using Hedges g was performed. Heterogeneity, risk of bias, and publication bias were assessed independently by multiple reviewers. Meta-regressions and sensitivity analyses were conducted to substantiate the overall results. The study followed the PRISMA reporting guideline. Main Outcomes and Measures: The main outcome was depressive symptoms as measured by validated depression scales at postintervention and follow-up. Results: Twenty-one studies involving 2441 participants (1148 [47.0%] boys; 1293 [53.0%] girls; mean [SD] age, 14 [3] years) were included. Meta-analysis of the postintervention differences revealed that physical activity interventions were associated with a reduction in depressive symptoms compared with the control condition (g = -0.29; 95% CI, -0.47 to -0.10; P = .004). Analysis of the follow-up outcomes in 4 studies revealed no differences between the physical activity and control groups (g = -0.39; 95% CI, -1.01 to 0.24; P = .14). Moderate study heterogeneity was detected (Q = 53.92; df = 20; P < .001; I2 = 62.9% [95% CI, 40.7%-76.8%]). The primary moderator analysis accounting for total physical activity volume, study design, participant health status, and allocation and/or assessment concealment did not moderate the main treatment effect. Secondary analyses demonstrated that intervention (ie, <12 weeks in duration, 3 times per week, unsupervised) and participant characteristics (ie, aged ≥13 years, with a mental illness and/or depression diagnosis) may influence the overall treatment effect. Conclusions and Relevance: Physical activity interventions may be used to reduce depressive symptoms in children and adolescents. Greater reductions in depressive symptoms were derived from participants older than 13 years and with a mental illness and/or depression diagnosis. The association with physical activity parameters such as frequency, duration, and supervision of the sessions remains unclear and needs further investigation.

Physical activity and exercise for cancer-related cognitive impairment among individuals affected by childhood cancer: a systematic review and meta-analysis.

BACKGROUND: Individuals affected by childhood cancer can have cognitive dysfunction that persists into adulthood and negatively affects quality of life. In this study, we aimed to evaluate the effects of physical activity and exercise on cognitive function among individuals affected by childhood cancer. METHODS: In this systematic review and meta-analysis, we searched seven databases (CINAHL Plus, Cochrane Library, Embase, MEDLINE, PsycINFO, SPORTDiscus, and Web of Science) and two clinical trial registries (ClinicalTrials.gov and the International Clinical Trials Registry Platform) for randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) published (or registered) from database inception to Jan 30, 2022, with no language restrictions. We included studies that compared the effects of physical activity or exercise interventions with controls (no intervention or usual care) on cognitive function among individuals diagnosed with any type of cancer at age 0-19 years. Two reviewers (JDKB and FR) independently screened records for eligibility and searched references of the selected studies; extracted study-level data from published reports; and assessed study risk of bias of RCTs and NRSIs using the Cochrane risk of bias tool for randomised trials (RoB 2) and Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I) tools, certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, and any adverse events. We used intention-to-treat data and unpublished data if available. Cognitive function was assessed by standardised cognitive performance measures (primary outcome) and by validated patient-reported measures (secondary outcome). A random-effects meta-analysis model using the inverse-variance and Hartung-Knapp methods was used to calculate pooled estimates (Hedges' g) and 95% CI values. We estimated the heterogeneity variance by the restricted maximum likelihood method and calculated I2 values to measure heterogeneity. We examined funnel plots and used Egger's regression test to assess for publication bias. This study is registered with PROSPERO, CRD42021261061. FINDINGS: We screened 12 425 titles and abstracts, which resulted in full-text assessment of 131 potentially relevant reports. We evaluated 22 unique studies (16 RCTs and six NRSIs) with data on 1277 individuals affected by childhood cancer and low-to-moderate risk of bias. Of the 1277 individuals, 674 [52·8%] were male and 603 [47·2%] were female; median age at study start was 12 (IQR 11-14) years, median time since the end of cancer treatment was 2·5 (IQR -1·1 to 3·0) years, and median intervention period was 12 [IQR 10-24] weeks. There was moderate-quality evidence that, compared with control, physical activity and exercise improved cognitive performance measures (five RCTs; Hedges' g 0·40 [95% CI 0·07-0·73], p=0·027; I2=18%) and patient-reported measures of cognitive function (13 RCTs; Hedges' g 0·26 [0·09-0·43], p=0·0070; I2=40%). No evidence of publication bias was found. Nine mild adverse events were reported. INTERPRETATION: There is moderate-certainty evidence that physical activity and exercise improves cognitive function among individuals affected by childhood cancer, which supports the use of physical activity for managing cancer-related cognitive impairment. FUNDING: Research Impact Fund of Research Grants Council of the Hong Kong University Grants Committee (R7024-20) and Seed Fund for Basic Research of the University of Hong Kong. COPYRIGHT: © 2022 Published by Elsevier Ltd. All rights reserved.

Prevalence and factors associated with demoralization in palliative care patients: A cross-sectional study from Hong Kong.

OBJECTIVES: Although demoralization is common among palliative care patients, it has not yet been examined empirically in the Hong Kong Chinese context. This study aims to examine (1) the prevalence of demoralization among community-dwelling palliative care patients in Hong Kong; (2) the percentage of palliative care patients who are demoralized but not depressed and vice versa; and (3) the association of socio-demographic factors, particularly family support, with demoralization. METHOD: A cross-sectional study targeting community-living palliative care patients in Hong Kong was conducted. A total of 54 patients were recruited by a local hospice and interviewed for completing a questionnaire which included measures of demoralization, depression, perceived family support, and demographic information. RESULTS: The prevalence of demoralization was 64.8%. Although there was overlap between demoralization and depression (52.8% meeting the criteria of both), 7.5% of depressed patients were not demoralized, and 13.2% of demoralized patients were not depressed. Participants who were not single and had more depressive symptoms and less family support had a significantly higher demoralization level. SIGNIFICANCE OF RESULTS: This is the first study which reports the prevalence of demoralization in Hong Kong. Demoralization was found common in community-living palliative care patients receiving medical social work services in Hong Kong. This study provides evidence of the importance of differentiating the constructs between demoralization and depression. It also provides an implication that those who are married, more depressed, and have the least family support could be the most vulnerable group at risk of demoralization. We recommend that early assessment of demoralization among palliative care patients be considered.

Effect of game-based high-intensity interval training program on the executive function of children with ADHD: Protocol of a randomized controlled trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common developmental disorder in childhood, with a 5%-6% worldwide prevalence. Children with ADHD often demonstrate impaired executive function, which is closely related to the development of the commonly observed behavioral problems such as inattention, impaired inhibition, and hyperactivity. The purpose of this study is to examine whether a game-based high-intensity interval training (HIIT) program can improve the executive function of children with ADHD, compared with a traditional structured aerobic exercise program and a non-treatment control group. METHODS/DESIGN: A total of 42 children with ADHD will be recruited to participate in this three-arm school-based randomized controlled trial. An 8-week specially designed game-based HIIT (GameHIIT) program and a traditional game-based structured aerobic exercise (GameSAE) program will be delivered to those children randomly assigned to these two intervention groups, while the children in the control group will maintain their regular physical activity over the same period. A number of outcome measures including executive function, cerebral hemodynamic response, physical activity, physical fitness, and enjoyment and adherence to the intervention will be assessed for both groups at baseline (T0), immediately after the intervention period (T1), and after the follow-up period (T2). DISCUSSION: HIIT has recently emerged as a feasible and efficacious strategy for increasing physical health outcomes and cognitive function, including executive function, in healthy young people. However, research has yet to investigate whether the executive function of children with ADHD can be effectively enhanced through HIIT. If, as hypothesized, GameHIIT program improves outcomes for children with ADHD, the present research will inform the development of targeted exercise programs that can be more broadly used with this particular population.

Effects of an internationalization at home (IAH) programme on cultural awareness among medical and nursing students in Hong Kong and Indonesia during the COVID-19 pandemic: a mixed-methods study.

BACKGROUND: The COVID-19 pandemic has severely impacted the learning experience of students by limiting their opportunities for face-to-face intercultural exchanges. Given the importance of cultural competence in medical education, there is a need to develop a programme that promotes cultural awareness, but that offers more flexibility in terms of outbound mobility. This study aims to evaluate the effectiveness of an internationalization at home programme and to explore the learning experiences of medical and nursing students from Hong Kong and Indonesia. METHODS: Students were recruited from two universities in Hong Kong and Indonesia. They attended an online internationalization at home programme designed by members of the research team from both countries. A mixed-methods study was conducted using a concurrent triangulation approach. A pre-test post-test design was used to evaluate the effects of the programme on cultural awareness, and four focus groups were conducted to explore the students' experiences in the programme. Quantitative and qualitative data were analysed by T-test and reflexive thematic analysis, respectively. Data were integrated and triangulated using joint displays by comparing findings from both sources. RESULTS: One hundred and forty-eight students from Hong Kong and Indonesia participated in the study. After the programme, there was a significant improvement in cultural awareness. Three themes were identified: (1) learning process: enjoyable, but a desire remains for face-to-face cross-cultural communication; (2) learning outcomes: gained cultural awareness, developed cultural sensitivity, had an opportunity to practice language and learn about new learning styles; (3) factors influencing learning outcomes: facilitators (micro-movie and active communication) and barriers (language barrier, inappropriate time arrangement, insufficient prior briefing). CONCLUSION: This programme achieved the learning outcomes by successfully enhancing the cultural awareness of students during a time of pandemic when outbound student exchanges were not possible. Further adaptations of the programme are required to enhance different learning outcomes.

Socially assistive robots for people with dementia: Systematic review and meta-analysis of feasibility, acceptability and the effect on cognition, neuropsychiatric symptoms and quality of life.

BACKGROUND: There is increasing interest in using robots to support dementia care but little consensus on the evidence for their use. The aim of the study is to review evidence about feasibility, acceptability and clinical effectiveness of socially assistive robots used for people with dementia. METHOD: We conducted a systematic review and meta-analysis. We searched MEDLINE, EMBASE, PsychINFO, CINHAL, IEEE Xplore Digital Library, and EI Engineering Village from inception to 04 - 02-2022 - included primary studies assessing feasibility, acceptability, or effectiveness of socially assistive robots for people with dementia. Two independent reviewers screened studies for eligibility, and assessed quality. Narrative synthesis prioritized higher quality studies, and random-effect meta-analyses compared robots with usual care (UC) or active control (AC) immediately after the intervention (short-term; ST) or long-term (LT) on cognition, neuropsychiatric symptoms, and quality of life. FINDINGS: 66 studies and four categories of robots were eligible: Companion robots (Pet and humanoid companion robots), telepresence communication robots, homecare assistive robots and multifunctional robots. PARO (companion robot seal) was feasible and acceptable but limited by its weight, cost, and sound. On meta-analysis, PARO had no ST or LT compared to UC or AC over 5-12 weeks on agitation (ST vs UC, 4 trials, 153 participants: pooled standardized mean difference (SMD) 0.25; - 0.57 to 0.06; LT vs UC; 2 trials, 77 participants, SMD = -0.24; - 0.94, 0.46), cognition (ST vs UC, 3 trials, 128 participants: SMD= 0.03; -0.32, 0.38), overall neuropsychiatric symptoms (ST vs UC, 3 trials, 169 participants: SMD= -0.01; -0.32, 0.29; ST vs AC, 2 trials, 145 participants: SMD =0.02, -0.71, 0.85), apathy (ST vs AC, 2 trials, 81 participants: SMD= 0.14; 0.29, 0.58), depression (ST vs UC, 4 trials, 181 participants; SMD= 0.08; -0.52, 0.69; LT vs UC: 2 trials, 77 participants: SMD =0.01; -0.75, 0.77), anxiety (ST vs UC: 2 trials, 104 participants, SMD= 0.24; -0.85, 1.33) and quality of life (ST vs UC, 2 trials, 127 participants: SMD=-0.05; -0.52, 0.42; ST vs AC: 2 trials, 159 participants, SMD =-0.36, -0.76, 0.05). Robotic animals, humanoid companion robots, telepresence robots and multifunctional robots were feasible and acceptable. However, humanoid companion robots have speech recognition problems, and telepresence robots and multifunctional robots were often difficult to use. There was mixed evidence about the feasibility of homecare robots. There was little evidence on any of these robots' effectiveness. CONCLUSION: Although robots were generally feasible and acceptable, there is no clear evidence that people with dementia derive benefit from robots for cognition, neuropsychiatric symptoms, or quality of life. We recommend that future research should use high quality designs to establish evidence of effectiveness.

Impact of COVID-19 on Mental Health of Palliative Care Professionals and Services: A Mixed-Methods Survey Study.

INTRODUCTION: This study aimed to examine the mental health of palliative care professionals in Hong Kong during the COVID-19 pandemic, the relationship of mental health with socio-demographic factors, and the impact of the pandemic on palliative care services. METHODS: A total of 142 palliative care professionals in Hong Kong participated in an online survey. The questionnaire includes measurements on depression, anxiety, perceived stress, post-traumatic stress, professional quality of life, items that measure the effect of COVID-19 on palliative care services, and one open-ended question for describing how the services were affected. Descriptive and multivariate regression analyses were conducted. Quantitative and qualitative data about the impact of COVID-19 on palliative care services were analyzed and triangulated using a mixed-methods approach. RESULTS: Up to 82%, 43%, and 42% of the participants felt moderately to highly stressed, anxious, and depressed, respectively, during the pandemic. Younger participants tended to have poorer mental health and professional quality of life. Around 82% felt stressed when communicating with patients and family members under the no-visiting policy during the pandemic. More than three-quarters of participants showed lack of confidence in the anti-epidemic policy of the government. Qualitative findings identified 3 themes affecting the provision of palliative care: 1. the tightening of restrictions on visitors; 2. the limited provision of services; and 3. staff deployment. CONCLUSIONS: Appropriate responses are required to give extra support to palliative care professionals during the pandemic and facilitate their coping with the impact of COVID-19 on the provision of palliative care.

Effects of aerobic exercise and resistance exercise on physical indexes and cardiovascular risk factors in obese and overweight school-age children: A systematic review and meta-analysis.

BACKGROUND: Obesity is a serious social and public health problem in the world, especially in children and adolescents. For school-age children with obesity, this stage is in the transition from childhood to adolescence, and both physical, psychological, and external environments will be full of challenges. Studies have showed that school-age children are the largest proportion of people who continue to be obese in adulthood. Physical exercise is considered as an effective way to control weight. Therefore, we focus on this point to study which factors will be improved to reduce childhood obesity. OBJECTIVE: To assess the effects of aerobic and resistance exercise on physical indexes, such as body mass index (BMI) and body fat percentage, and cardiovascular risk factors such as VO2peak, triglycerides (TG) and low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), insulin and insulin resistance in school-age children who are overweight or obese. METHOD: PubMed, SPORTDiscus, Medline, Cochrane-Library, Scopus, Ovid and Web of Science were searched to locate studies published between 2000 and 2021 in obese and overweight school-age children between 6-12 years old. The articles are all randomized controlled trials (RCTs) and in English. Data were synthesized using a random-effect or a fixed-effect model to analyze the effects of aerobic and resistance exercise on six elements in in school-age children with overweight or obese. The primary outcome measures were set for BMI. RESULTS: A total of 13 RCTs (504 participants) were identified. Analysis of the between-group showed that aerobic and resistance exercise were effective in improving BMI (MD = -0.66; p < 0.00001), body fat percentage (MD = -1.29; p = 0.02), TG (std.MD = -1.14; p = 0.005), LDL (std.MD = -1.38; p = 0.003), TC (std.MD = -0.77; p = 0.002), VO2peak (std.MD = 1.25; p = 0.001). However, aerobic and resistance exercise were not significant in improving HDL (std.MD = 0.13; p = 0.27). CONCLUSIONS: Aerobic exercise and resistance exercise are associated with improvement in BMI, body fat percentage, VO2peak, TG, LDL, TC, while not in HDL in school-age children with obesity or overweight. Insulin and insulin resistance were not able to be analyzed in our review. However, there are only two articles related to resistance exercise in children with obesity and overweight at school age, which is far less than the number of 12 articles about aerobic exercise, so we cannot compare the effects of the two types of exercises.

Tubulin acetylation promotes penetrative capacity of cells undergoing radial intercalation.

Post-translational modification of tubulin provides differential functions to microtubule networks. Here, we address the role of tubulin acetylation on the penetrative capacity of cells undergoing radial intercalation, which is the process by which cells move apically, insert between outer cells, and join an epithelium. There are opposing forces that regulate intercalation, namely, the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell. Positively and negatively modulating tubulin acetylation in intercalating cells alters the developmental timing such that cells with more acetylation penetrate faster. We find that intercalating cells preferentially penetrate higher-order vertices rather than the more prevalent tricellular vertices. Differential timing in the ability of cells to penetrate different vertices reveals that lower-order vertices represent more restrictive sites of insertion. We shift the accessibility of intercalating cells toward more restrictive junctions by increasing tubulin acetylation, and we provide a geometric-based mathematical model that describes our results.

Spatial distribution of B cells and lymphocyte clusters as a predictor of triple-negative breast cancer outcome.

While tumor infiltration by CD8+ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method 'occupancy') to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.

Physics approaches to the spatial distribution of immune cells in tumors.

The goal of immunotherapy is to mobilize the immune system to kill cancer cells. Immunotherapy is more effective and, in general, the prognosis is better, when more immune cells infiltrate the tumor. We explore the question of whether the spatial distribution rather than just the density of immune cells in the tumor is important in forecasting whether cancer recurs. After reviewing previous work on this issue, we introduce a novel application of maximum entropy to quantify the spatial distribution of discrete point-like objects. We apply our approach to B and T cells in images of tumor tissue taken from triple negative breast cancer patients. We find that the immune cells are more spatially dispersed in good clinical outcome (no recurrence of cancer within at least 5 years of diagnosis) compared to poor clinical outcome (recurrence within 3 years of diagnosis). Our results highlight the importance of spatial distribution of immune cells within tumors with regard to clinical outcome, and raise new questions on their role in cancer recurrence.

The Use of Modified Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy Program for Family Caregivers of People Living with Dementia: A Feasibility Study.

PURPOSE: The aim of this study was to investigate the feasibility and preliminary efficacy of a modified mindfulness-based stress reduction (MBSR) program and mindfulness-based cognitive therapy (MBCT) program for reducing the stress, depressive symptoms, and subjective burden of family caregivers of people with dementia (PWD). METHODS: A prospective, parallel-group, randomized controlled trial design was adopted. Fifty-seven participants were recruited from the community and randomized into either the modified MBSR group (n = 27) or modified MBCT group (n = 26), receiving seven face-to-face intervention sessions for more than 16 weeks. Various psychological outcomes were measured at baseline (T0), immediately after intervention (T1), and at the 3-month follow-up (T2). RESULTS: Both interventions were found to be feasible in view of the high attendance (more than 70.0%) and low attrition (3.8%) rates. The mixed analysis of variance (ANOVA) results showed positive within-group effects on perceived stress (p = .030, Cohen's d = 0.54), depressive symptoms (p = .002, Cohen's d = 0.77), and subjective caregiver burden (p < .001, Cohen's d = 1.12) in both interventions across the time points, whereas the modified MBCT had a larger effect on stress reduction, compared with the modified MBSR (p = .019). CONCLUSION: Both the modified MBSR and MBCT are acceptable to family caregivers of PWD. Their preliminary effects were improvements in stress, depressive symptoms, and subjective burden. The modified MBCT may be more suitable for caregivers of PWD than the MBSR. A future clinical trial is needed to confirm their effectiveness in improving the psychological well-being of caregivers of PWD.

Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila.

A striking feature of micro-RNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a micro-RNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this micro-RNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of micro-RNA cluster members were also constructed. Expression of individual micro-RNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient micro-RNAs together (miR-5/4/286/3/309) or more recently evolved clustered micro-RNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed downregulation of leg-patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of micro-RNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct micro-RNAs. Considered together, the micro-RNA targets and the evolutionary ages of each micro-RNA in the cluster demonstrate the importance of micro-RNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing micro-RNAs. Key words: micro-RNA, cluster, evolution.

Why Phonon Scattering in Glasses is Universally Small at Low Temperatures.

We present a novel view of the standard model of tunneling two level systems (TLSs) to explain the puzzling universal value of a quantity, C∼3×10^{-4}, that characterizes phonon scattering in glasses below 1 K as reflected in thermal conductivity, ultrasonic attenuation, internal friction, and the change in sound velocity. Physical considerations lead to a broad distribution of phonon-TLS couplings that (1) exponentially renormalize tunneling matrix elements, and (2) reduce the TLS density of states through TLS-TLS interactions. We find good agreement between theory and experiment for a variety of individual glasses.