Sleep Problems in Children with ADHD: Associations with Internalizing Symptoms and Physical Activity.

Children with attention deficit hyperactivity disorder (ADHD) experience high rates of sleep problems and are at increased risk for developing internalizing problems. This study aimed to examine the association of sleep problems and physical activity with internalizing symptoms in children with ADHD. This cross-sectional study included 188 children with ADHD (M age = 8.60 ± 1.38, 78.7% boys). Self-reported questionnaires were used to assess sleep problems (Pittsburgh Sleep Quality Index [PSQI]) and internalizing symptoms (Depression Anxiety Stress Scale 21 [DASS 21]). The presence of sleep problems was defined as a PSQI score > 5. Physical activity was recorded by an ActiGraph GT9X Link accelerometer for 7 consecutive days. In total, 111 children with ADHD presented with sleep problems (59%). Compared with their counterparts without sleep problems, children with sleep problems spent less time in daily moderator-to-vigorous physical activity (MVPA) (F = 15.35, η2 = .079), had a lower proportion of meeting the WHO-recommended 60 min of daily MVPA guideline (F = 9.57, η2 = .050), and showed more internalizing symptoms: depression (F = 10.09, η2 = .053), anxiety (F = 15.84, η2 = .081), and stress (F = 6.98, η2 = .037). BMI, daytime dysfunction of PSQI, and MVPA guideline attainment were significantly associated with internalizing symptoms in children with ADHD. Daytime dysfunction of PSQI is associated with more severe internalizing symptoms, and MVPA guideline attainment may reduce the likelihood of developing depression and anxiety in children with ADHD. Future studies are needed to examine the long-term effects of sleep on internalizing symptoms and the effects of PA-based interventions on sleep and internalizing symptoms in children with ADHD, respectively.

Managing Uncertainty and Loneliness: Protective and Risk Factors Impacting on Older People's Mental Health in Hong Kong.

This study investigated the roles of loneliness and prospective intolerance of uncertainty (IU-P) on mental health, and identified the sources of stress and joy during the COVID-19 in Hong Kong. Two thousand two hundred and fifty-eight older adults completed the survey. Older adults who had higher levels of loneliness and IU-P were more likely to have poor mental health. IU-P was found to partially and positively mediate the relationship between loneliness and mental health. Top stressors were contracting the virus, uncertainty about the future, and loneliness; while family/friends, peace of mind, and hobbies were identified as protective factors.

Antiproliferative Activity of Cephalotaxus Esters: Overcoming Chemoresistance.

INTRODUCTION: Omacetaxine, a semisynthetic form of Homoharringtonine (HHT), was approved for the treatment of Chronic Myeloid Leukemia (CML). Previously, we have published the synthesis of this natural alkaloid and three of its derivatives: Deoxyharringtonine (DHT), Deoxyhomoharringtonine (DHHT), and Bis(demethyl)-deoxyharringtonine (BDHT), and reported its refractory activity against the HL-60/RV+ cells over-expressing P-glycoprotein 1 (MDR1). METHODS: In this study, we have explored the extent of this resistance by first expanding the panel of established cell lines and using a panel of 21 leukemia patient-derived primary cells. RESULTS: Herein, we have reported consistent resistance to HTT of K562-derived cells and to mitoxantrone of MES-SA/MX2-derived cells; all of them have been found to overexpress MDR1, while we have found U87MG-ABCG2 and H69AR cells to be very sensitive to HTT. In contrast, DHT, DHHT, and BDHT seemingly overcame this resistance due to the changes made to the acyl chain of HTT, rendering the derivatives less susceptible to efflux. Surprisingly, the leukemia primary cells were very sensitive to HHT and its derivatives with low nanomolar potencies, followed by a new class of CDC7 kinase inhibitors, the anthracycline class of topoisomerase inhibitors, the DNA intercalator actinomycin-D, and the vinca alkaloid class of microtubule inhibitors. The mechanism of cell death induced by HTT and DHHT was found to be mediated via caspase 3 cleavage, leading to apoptosis. CONCLUSION: Taken together, our results confirm that HHT is a substrate for MDR1. It opens the door to a new opportunity to clinically evaluate HHT and its derivatives for the treatment of AML and other cancers.

Impact of a physical exercise intervention on psychological resilience and mental ill-being in medical-naïve children with attention-deficit/hyperactivity disorder: a pilot randomised controlled trial.

The study aimed to evaluate whether a 12-week physical exercise intervention would improve psychological resilience and mental ill-being (e.g. internalising and externalising symptoms) in medical-naïve children with Attention-Deficit/Hyperactivity Disorder (ADHD). In a parallel two-group randomised controlled trial (RCT) design, 30 children between 8-12 years (Mage = 8.62 ± 1.37) formally diagnosed with ADHD were assigned to a 12-week physical exercise intervention group (three sessions per week for 60 mins, moderate-to-vigorous physical activity [MVPA] intensity) or a control group (treatment as usual). Psychological resilience was measured by a self-reported Chinese version of the 25-item Connor-Davidson Resilience Scale, and mental ill-being was assessed by a parent-reported Chinese version of the 113-item Achenbach's Child Behavior Checklist. The 12-week physical exercise intervention with MVPA level revealed a significant improvement in psychological resilience (F = 4.82, p = .038) and a significant reduction in internalising symptoms (e.g. anxiety/depressed, withdrawn/depressed, and somatic complaints) (F = 7.11, p = .013) and externalising symptoms (e.g. rule-breaking behaviour and aggressive behaviour) (F = 21.09, p < .001) in the intervention group but not in the control group. Moderate correlations were revealed between the changes in psychological resilience and the changes in internalizing (r = -.557, p = .031) and externalising symptoms (r = -.647, p = .009) in the intervention groups (n = 15). The findings of this study provide initial support for the efficacy of physical exercise intervention on psychological resilience and mental ill-being and for the potential mechanisms of psychological resilience under the effects of exercise-induced mental ill-being improvements in children with ADHD.

Are Older Adults More Prosocial Than Younger Adults? A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Prosociality refers to voluntary behaviors that intend to benefit others. Most of the existing literature suggests that older adults tend to act more prosocially compared to younger adults, whereas some studies show that older adults might not be that prosocial under certain conditions. The current study aimed to summarize the mixed findings and quantify the age difference in prosociality by conducting a qualitative systematic review and a quantitative meta-analysis. RESEARCH DESIGN AND METHODS: Literature search was conducted based on 5 databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and this review was registered at PROSPERO (CRD42022333373). RESULTS: Based on the qualitative synthesis of 51 studies, older adults (n = 109,911) were more prosocial than younger adults (n = 68,501). The meta-analysis of 46 studies further supported this age effect (Hedges' g = 0.31, 95% confidence interval [0.24, 0.37]), and this age effect might be moderated by the types of prosociality. We discovered a moderate age effect in sharing (Hedges' g = 0.53), but a nonsignificant age effect in helping (Hedges' g = 0.11), comforting (Hedges' g = -0.20), or mixed prosociality (Hedges' g = 0.15). Additionally, the age effect was only significant when older adults had higher socioeconomic status than younger adults. DISCUSSION AND IMPLICATIONS: Future research should develop more comprehensive measures of prosociality, examine more variables that influence aging and prosociality, and investigate the neural mechanism(s) of prosociality to achieve a thorough understanding of the age difference in prosociality.

Reducing Peptidoglycan Crosslinking by Chemical Modulator Reverts ß-lactam Resistance in Methicillin-Resistant Staphylococcus aureus.

Small molecule can be utilized to restore the effectiveness of existing major classes of antibiotics against antibiotic-resistant bacteria. In this study, it is demonstrated that celastrol, a natural compound, can modify the bacterial cell wall and subsequently render bacteria more suceptible to ß-lactam antibiotics. It is shown that celastrol leads to incomplete cell wall crosslinking by modulating levels of c-di-AMP, a secondary messenger, in methicillin-resistant Staphylococcus aureus (MRSA). This mechanism enables celastrol to act as a potentiator, effectively rendering MRSA susceptible to a range of penicillins and cephalosporins. Restoration of in vivo susceptibility of MRSA to methicillin is also demonstrated using a sepsis animal model by co-administering methicillin along with celastrol at a much lower amount than that of methicillin. The results suggest a novel approach for developing potentiators for major classes of antibiotics by exploring molecules that re-program metabolic pathways to reverse ß-lactam-resistant strains to susceptible strains.

Identification of Leishmania donovani PEX5-PTS1 Interaction Inhibitors through Fluorescence Polarization-Based High-Throughput Screening.

Leishmaniasis, an infectious disease caused by pathogenic Leishmania parasites, affects millions of people in developing countries, and its re-emergence in developed countries, particularly in Europe, poses a growing public health concern. The limitations of current treatments and the absence of effective vaccines necessitate the development of novel therapeutics. In this study, we focused on identifying small molecule inhibitors which prevents the interaction between peroxin 5 (PEX5) and peroxisomal targeting signal 1 (PTS1), pivotal for kinetoplastid parasite survival. The Leishmania donovani PEX5, containing a C-terminal tetratricopeptide repeat (TPR) domain, was expressed and purified, followed by the quantification of kinetic parameters of PEX5-PTS1 interactions. A fluorescence polarization-based high-throughput screening assay was developed and small molecules inhibiting the LdPEX5-PTS1 interaction were discovered through the screening of a library of 51,406 compounds. Based on the confirmatory assay, nine compounds showed half maximal inhibitory concentration (IC50) values ranging from 3.89 to 24.50 µM. In silico docking using a homology model of LdPEX5 elucidated that the molecular interactions between LdPEX5 and the inhibitors share amino acids critical for PTS1 binding. Notably, compound P20 showed potent activity against the growth of L. donovani promastigotes, L. major promastigotes, and Trypanosoma brucei blood stream form, with IC50 values of 12.16, 19.21, and 3.06 µM, respectively. The findings underscore the potential of targeting LdPEX5-PTS1 interactions with small molecule inhibitors as a promising strategy for the discovery of new anti-parasitic compounds.

High-throughput screening of small-molecules libraries identified antibacterials against clinically relevant multidrug-resistant A. baumannii and K. pneumoniae.

BACKGROUND: The current pipeline for new antibiotics fails to fully address the significant threat posed by drug-resistant Gram-negative bacteria that have been identified by the World Health Organization (WHO) as a global health priority. New antibacterials acting through novel mechanisms of action are urgently needed. We aimed to identify new chemical entities (NCEs) with activity against Klebsiella pneumoniae and Acinetobacter baumannii that could be developed into a new treatment for drug-resistant infections. METHODS: We developed a high-throughput phenotypic screen and selection cascade for generation of hit compounds active against multidrug-resistant (MDR) strains of K. pneumoniae and A. baumannii. We screened compound libraries selected from the proprietary collections of three pharmaceutical companies that had exited antibacterial drug discovery but continued to accumulate new compounds to their collection. Compounds from two out of three libraries were selected using "eNTRy rules" criteria associated with increased likelihood of intracellular accumulation in Escherichia coli. FINDINGS: We identified 72 compounds with confirmed activity against K. pneumoniae and/or drug-resistant A. baumannii. Two new chemical series with activity against XDR A. baumannii were identified meeting our criteria of potency (EC50 ≤50 µM) and absence of cytotoxicity (HepG2 CC50 ≥100 µM and red blood cell lysis HC50 ≥100 µM). The activity of close analogues of the two chemical series was also determined against A. baumannii clinical isolates. INTERPRETATION: This work provides proof of principle for the screening strategy developed to identify NCEs with antibacterial activity against multidrug-resistant critical priority pathogens such as K. pneumoniae and A. baumannii. The screening and hit selection cascade established here provide an excellent foundation for further screening of new compound libraries to identify high quality starting points for new antibacterial lead generation projects. FUNDING: BMBF and GARDP.

An AI-empowered indoor digital contact tracing system for COVID-19 outbreaks in residential care homes.

An AI-empowered indoor digital contact-tracing system was developed using a centralized architecture and advanced low-energy Bluetooth technologies for indoor positioning, with careful preservation of privacy and data security. We analyzed the contact pattern data from two RCHs and investigated a COVID-19 outbreak in one study site. To evaluate the effectiveness of the system in containing outbreaks with minimal contacts under quarantine, a simulation study was conducted to compare the impact of different quarantine strategies on outbreak containment within RCHs. The significant difference in contact hours between weekdays and weekends was observed for some pairs of RCH residents and staff during the two-week data collection period. No significant difference between secondary cases and uninfected contacts was observed in a COVID-19 outbreak in terms of their demographics and contact patterns. Simulation results based on the collected contact data indicated that a threshold of accumulative contact hours one or two days prior to diagnosis of the index case could dramatically increase the efficiency of outbreak containment within RCHs by targeted isolation of the close contacts. This study demonstrated the feasibility and efficiency of employing an AI-empowered system in indoor digital contact tracing of outbreaks in RCHs in the post-pandemic era.

Examining the Utility of a Multiple Group Membership Intervention for Alleviating the Effects of Age-Based Stereotype Threat on Older adults' Memory Performance.

This study examined the effectiveness of a multiple group membership intervention for reducing the negative effects of age-based stereotype threat (ABST) on older adults' objective memory performance and subjective memory concerns. Healthy older adults (N = 68) were randomly allocated to an ABST + threat-removal (ABST+TR) or ABST + active-control (ABST+AC) condition. After activating ABST, the ABST+TR condition completed a group-listing task and the ABST+AC condition completed a meal-listing task. Participants then completed the Rey Auditory Verbal Learning Test (RAVLT) and Everyday Memory Questionnaire - Revised. One significant difference was found in memory performance between conditions; specifically, after controlling for age, gender, and number of items listed, those in the ABST+TR condition performed significantly better on the RAVLT memory interference trial. Further, listing a greater number of group memberships was associated with better memory performance in the ABST+TR condition. No significant difference was found in subjective memory concerns between the ABST+TR condition and the ABST+AC condition. Overall, the current findings indicated that raising the salience of multiple group memberships offered limited protection for older adults' cognitive test performance in the context of ABST.

Inhibition of DNMT3B expression in activated hepatic stellate cells overcomes chemoresistance in the tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a complex disease associated with a plethora of environmental and genetic/hereditary causative risk factors, more so than other oncological indications. Additionally, patients with HCC exhibit fibrosis, cirrhosis, and liver-related disease. This complicated etiology can affect the disease course and likely contributes to its poor prognosis. In this study, we aimed to improve HCC therapy by evaluating combination treatment using anti-cancer and anti-fibrosis drugs via identification of novel anti-fibrosis drugs. We performed high-throughput screening of 10,000 compounds to identify hepatic fibrosis inhibitors through morphometry analysis of multicellular hepatic spheroid (MCHS) models and identified CHIR-99021 as a candidate anti-fibrotic drug. Treatment with CHIR-99021 induced loss of cell-cell interactions and suppression of extracellular matrix-related protein expression via reprogramming of hepatic stellate cell (HSC) activation in MCHSs. In particular, CHIR-99021 regulated DNMT3B expression only in activated HSCs. Moreover, CHIR-99021 markedly improved the efficacy of sorafenib in HCC- multicellular tumor spheroids in vitro and through induction of apoptosis by decreasing DNMT3B expression in vivo. In summary, these findings suggest that targeting HSC reprogramming by attenuation of DNMT3B expression in the tumor environment might represent a promising therapeutic strategy for liver fibrosis and HCC.

Cost-utility analysis of a telehealth psychological support intervention for people with primary brain tumor: Telehealth Making Sense of brain tumor.

OBJECTIVE: To undertake an economic evaluation of a telehealth psychological support intervention for patients with primary brain tumor (PBT). METHODS: A within-trial cost-utility analysis over 6 months was performed comparing a tailored telehealth-psychological support intervention with standard care (SC) in a randomized control trial. Data were sourced from the Telehealth Making Sense of Brain Tumor (Tele-MAST) trial survey data, project records, and administrative healthcare claims. Quality-adjusted life years (QALYs) were calculated based on the EuroQol-5D-5L. Non-parametric bootstrapping with 2000 iterations was used to determine sampling uncertainty. Multiple imputation was used for handling missing data. RESULTS: The Tele-MAST trial included 82 participants and was conducted in Queensland, Australia during 2018-2021. When all healthcare claims were included, the incremental cost savings from Tele-MAST were -AU$4,327 (95% CI: -$8637, -$18) while incremental QALY gains were small at 0.03 (95% CI: -0.02, 0.08). The likelihood of Tele-MAST being cost-effective versus SC was 87% at a willingness-to-pay threshold of AU$50,000 per QALY gain. When psychological-related healthcare costs were included only, the incremental cost per QALY gain was AU$10,685 (95% CI: dominant, $24,566) and net monetary benefits were AU$534 (95% CI: $466, $602) with a 65% likelihood of the intervention being cost-effective. CONCLUSIONS: Based on this small randomized controlled trial, the Tele-MAST intervention is a cost-effective intervention for improving the quality of life of people with PBT in Australia. Patients receiving the intervention incurred significantly lower overall healthcare costs than patients in SC. There was no significant difference in costs incurred for psychological health services.

The perspectives of participants with traumatic brain injury on prospective memory rehabilitation incorporating compensatory and metacognitive skills training.

OBJECTIVE: Patient feedback is rarely gathered systematically in cognitive rehabilitation research. This study examined the perceptions and experiences of people with traumatic brain injury (TBI) who participated in a trial of a 6-session educational program for the rehabilitation of prospective memory (PM) impairment. METHODS: A mixed methods design was used with 47 participants with TBI who completed a compensatory strategy training program (COMP) or COMP plus metacognitive strategy training program (COMP-MST) delivered by an occupational therapist. Data were collected via a participant survey, extracts from progress notes, and audiotaped discussions about learnings from the program during the final session. RESULTS: Participants from both programs were highly satisfied and perceived improvements in everyday PM performance post-intervention. Elements that were highly valued include setting individualised client-centred goals, repetitive training of strategy use, establishing habits and routines, and receiving experiential, verbal, and written feedback.Changes including more therapy sessions were recommended. CONCLUSIONS: Both the COMP and COMP-MST programs were perceived as effective by participants with TBI in improving their PM performance in everyday life using compensatory strategies such as assistive technology. PRACTICE IMPLICATIONS: Routine collection of patient feedback on cognitive rehabilitation can provide valuable information to support person-centred implementation of clinical practice guidelines.

A Health App for Post-Pandemic Years (HAPPY) for people with physiological and psychosocial distress during the post-pandemic era: Protocol for a randomized controlled trial.

Objective: This article describes a protocol for a randomized controlled trial to evaluate the effects of a three-level Health App for Post-Pandemic Years (HAPPY) on alleviating post-pandemic physiological and psychosocial distress. Methods: Convenience and snowball sampling methods will be used to recruit 814 people aged 18+ with physiological and/or psychosocial distress. The experimental group will receive a 24-week intervention consisting of an 8-week regular supervision phase and a 16-week self-help phase. Based on their assessment results, they will be assigned to receive interventions on mindfulness, energy conservation techniques, or physical activity training. The waitlist control group will receive the same intervention in Week 25. The primary outcome will be changes in psychosocial distress, measured using the Kessler Psychological Distress Scale (K10). Secondary outcomes will include changes in levels of fatigue (Chinese version of the Brief Fatigue Inventory), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index), pain intensity (Numeric Rating Scale), positive appraisal (Short version of the 18-item Cognitive Emotion Regulation Questionnaire), self-efficacy (Chinese version of the General Self-efficacy Scale), depression and anxiety (Chinese version of the 21-item Depression Anxiety Stress Scale), and event impact (Chinese version of the 22-item Impact of Event Scale-Revised). All measures will be administered at baseline (T0), Week 8 after the supervision phase (T1), and 24 weeks post-intervention (T2). A generalized estimating equations model will be used to examine the group, time, and interaction (Time × Group) effect of the interventions on the outcome assessments (intention-to-treat analysis) across the three time points, and to compute a within-group comparison of objective physiological parameters and adherence to the assigned interventions in the experimental group. Conclusions: The innovative, three-level mobile HAPPY app will promote beneficial behavioral strategies to alleviate post-pandemic physiological and psychosocial distress. Trial registration: ClinicalTrials.gov, NCT05459896. Registered on 15 July 2022.

A Genome-Wide RNAi Screen Reveals Common Host-Virus Gene Signatures: Implication for Dengue Antiviral Drug Discovery.

Dengue is the most common mosquito-borne viral disease that in recent years has become a major international public health concern. Dengue is a tropical neglected disease with increasing global incidences, affecting millions of people worldwide, and without the availability of specific treatments to combat it. The identification of host-target genes essential for the virus life cycle, for which effective modulators may already exist, would provide an alternative path to a rapid drug development of the much needed antidengue agents. For this purpose, we performed the first genome-wide RNAi screen, combining two high-content readouts for dengue virus infection (DENV E infection intensity) and host cell toxicity (host cell stained nuclei), against an arrayed lentiviral-based short hairpin RNA library covering 16,000 genes with a redundancy of at least 5 hairpins per gene. The screen identified 1924 gene candidates in total; of which, 1730 gene candidates abrogated dengue infection, whereas 194 gene candidates were found to enhance its infectivity in HEK293 cells. A first pass clustering analysis of hits revealed a well-orchestrated gene-network dependency on host cell homeostasis and physiology triggering distinct cellular pathways for infectivity, replication, trafficking, and egress; a second analysis revealed a comprehensive gene signature of 331 genes common to hits identified in 28 published RNAi host-viral interaction screens. Taken together, our findings provide novel antiviral molecular targets with the potential for drug discovery and development.

Efficacy of non-pharmacological interventions on executive functions in children and adolescents with ADHD: A systematic review and meta-analysis.

OBJECTIVE: Although front-line doctors recommend medications, this kind of treatment has limited efficacy in improving executive functions (EFs) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). This study explored the effects of non-pharmacological intervention on EFs in children and adolescents with ADHD. METHODS: In accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines, we searched seven electronic databases: APA PsycINFO, CINAHL Complete, EMBASE, ERIC, Medline, Pubmed, and Web of Science, from inception to March 2022. Two authors independently screened studies for eligibility, extracted data, and assessed bias risk using the Physiotherapy Evidence Database scale. Our analyses included randomized controlled trials and non-randomized comparison studies of non-pharmacological interventions and assessed EFs through neurocognitive tasks in children and adolescents between 5 and 18 years. RESULTS: Sixty-seven studies with 3147 participants met the inclusion criteria. The final meta-analysis included 74 independent interventions categorized into six categories: cognitive training, EF-specific curriculum, game-based training, mindfulness practice, neurofeedback training, and physical exercise. Overall, non-pharmacological interventions (combined) produced significant moderate to large effects on overall EFs in children and adolescents with ADHD (g=0.673). Physical exercise had a large positive effect on domain-specific EFs, including inhibitory control (g=0.900) and cognitive flexibility (g=1.377). Cognitive training had a large training effect on working memory (g=0.907), and an EF-specific curriculum had a small to moderate beneficial effect on planning performance (g=0.532). CONCLUSION: Non-pharmacological interventions, particularly physical exercise, cognitive training, and an EF-specific curriculum, appear to have beneficial effects on EFs in children and adolescents with ADHD.

Evaluation of the telehealth making sense of brain tumor psychological support intervention for people with primary brain tumor and their caregivers: A randomized controlled trial.

OBJECTIVE: This pragmatic randomized control trial aimed to evaluate clinical efficacy of the Making Sense of Brain Tumour program delivered via videoconferencing (Tele-MAST) for improving mental health and quality of life (QoL) relative to standard care in individuals with primary brain tumor (PBT). METHOD: Adults with PBT experiencing at least mild distress (Distress Thermometer ≥4) and caregivers were randomly allocated to the 10-session Tele-MAST program or standard care. Mental health and QoL were assessed pre-intervention, post-intervention (primary endpoint), and 6-weeks and 6-months follow-up. The primary outcome was clinician-rated depressive symptoms on the Montgomery-Asberg Depression Rating Scale. RESULTS: 82 participants with PBT (34% benign, 20% lower-grade glioma, 46% high-grade glioma) and 36 caregivers were recruited (2018-2021). Controlling for baseline functioning, Tele-MAST participants with PBT had lower depressive symptoms at post-intervention (95% CI: 10.2-14.6, vs. 15.2-19.6, p = 0.002) and 6-weeks post-intervention (95% CI: 11.5-15.8 vs. 15.6-19.9, p = 0.010) than standard care, and were almost 4 times more likely to experience clinically reduced depression (OR, 3.89; 95% CI: 1.5-9.9). Tele-MAST participants with PBT also reported significantly better global QoL, emotional QoL and lower anxiety at post-intervention and 6-weeks post-intervention than standard care. There were no significant intervention effects for caregivers. At 6-months follow-up participants with PBT who received Tele-MAST reported significantly better mental health and QoL relative to pre-intervention. CONCLUSIONS: Tele-MAST was found to be more effective for reducing depressive symptoms at post-intervention than standard care for people with PBT but not caregivers. Tailored and extended psychological support may be beneficial for people with PBT.

Stigma and health inequality experienced by ethnic minorities during the COVID-19 pandemic in a Chinese community: an implication to health policymakers.

Introduction: Ethnic minorities are considered one of the most vulnerable groups during the COVID-19 pandemic. However, the explanatory pathway of how their disadvantaged experiences during epidemics are related to the embedded and longstanding stigmas against them and how these embedded stigmas can affect their resilience in disease outbreaks are not well understood. This study investigated the experiences of ethnic minorities in the COVID-19 pandemic, and how their experiences were related to the embedded stigma toward them. Methods: This study adopted a qualitative approach, interviewed 25 individuals (13 women and 12 men) from ethnic minority groups residing in Hong Kong from August 2021 to February 2022 in a semi-structured format. Thematic analysis was conducted to analyze the data. Results: The participants were isolated and stereotyped as infectious during the COVID-19 pandemic at community and institutional levels. Their experiences did not occur suddenly during the pandemic but were embedded in the longstanding segregation and negative stereotypes toward ethnic minorities in different aspects of life before the pandemic. These negative stereotypes affected their resilience in living and coping with the pandemic. Conclusion: The participants' experiences during the COVID-19 pandemic were mostly disadvantageous and predominantly initiated by the mainstream stigmatization toward them by the local Chinese residents and government. Their disadvantaged experiences in the pandemic should be traced to the embedded social systems, imposing structural disparities for ethnic minorities when accessing social and medical resources during a pandemic. Because of the preexisting stigmatization and social seclusion of ethnic minorities in Hong Kong, the participants experienced health inequality, which stemmed from social inequality and the power differential between them and the Chinese locals. The disadvantaged situation of the participants negatively affected their resilience to the pandemic. To enable ethnic minorities better cope with future epidemics, merely providing assistance to them during an epidemic is barely adequate, but a more supportive and inclusive social system should be established for them in the long run.

A pattern-centered analysis of adolescents' concerns and hopes about future crises: Differences in ways of coping and personal adjustment.

INTRODUCTION: Many adolescents are concerned about global and future crises, such as the health of the planet or terrorism/safety. Yet, adolescents can also express hope about the future. Thus, asking adolescents about their concern and hope could yield subgroups with different ways of coping and personal adjustment. METHOD: Australian adolescents (N = 863; age 10-16) completed surveys to report their concern (worry and anger) and hope about the planet, safety, jobs, income, housing, and technology, as well as their active and avoidant coping, depression, and life satisfaction. RESULTS: Four distinct subgroups were identified using cluster analysis: Hopeful (low on concern and high on hope across all issues, 32%), Uninvolved (low in concern and hope; 26%), Concerned about the Planet (CP, 27%), and Concerned about Future Life (CFL, 15%). When compared (adjusting for age, sex, and COVID timing), the CP subgroup was highest in active coping (e.g., taking action) but moderate in personal adjustment. Hopeful had the most positive adjustment, whereas CFL had the poorest adjustment. Uninvolved were lowest in coping but moderate in adjustment. CONCLUSIONS: Findings suggest ways of coping and adjustment may not always align, in that CP is connected with more active coping but also some cost to personal adjustment, whereas Hopeful is associated with optimal adjustment but perhaps at the cost of active coping. In addition, although CFL adolescents emerged as the at-risk group, the low levels of hope and coping in Uninvolved adolescents raise the possibility that they are at risk of future problems.

Collaborative Virtual Screening Identifies a 2-Aryl-4-aminoquinazoline Series with Efficacy in an In Vivo Model of Trypanosoma cruzi Infection.

Probing multiple proprietary pharmaceutical libraries in parallel via virtual screening allowed rapid expansion of the structure-activity relationship (SAR) around hit compounds with moderate efficacy against Trypanosoma cruzi, the causative agent of Chagas Disease. A potency-improving scaffold hop, followed by elaboration of the SAR via design guided by the output of the phenotypic virtual screening efforts, identified two promising hit compounds 54 and 85, which were profiled further in pharmacokinetic studies and in an in vivo model of T. cruzi infection. Compound 85 demonstrated clear reduction of parasitemia in the in vivo setting, confirming the interest in this series of 2-(pyridin-2-yl)quinazolines as potential anti-trypanosome treatments.