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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' gâ =â 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.
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Comportamento Social , Humanos , Idoso , Fatores Etários , Adulto , Adulto Jovem , Envelhecimento/psicologia , Altruísmo , Masculino , FemininoRESUMO
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.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Peptidoglicano , Resistência beta-Lactâmica , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Peptidoglicano/metabolismo , Resistência beta-Lactâmica/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Testes de Sensibilidade Microbiana , Camundongos , Triterpenos Pentacíclicos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Parede Celular/metabolismo , Parede Celular/efeitos dos fármacos , beta-Lactamas/farmacologia , Triterpenos/farmacologia , Triterpenos/metabolismoRESUMO
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.
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Ensaios de Triagem em Larga Escala , Leishmania donovani , Simulação de Acoplamento Molecular , Receptor 1 de Sinal de Orientação para Peroxissomos , Proteínas de Protozoários , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Receptor 1 de Sinal de Orientação para Peroxissomos/metabolismo , Receptor 1 de Sinal de Orientação para Peroxissomos/química , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Polarização de Fluorescência/métodos , Ligação Proteica , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Antiprotozoários/farmacologia , Antiprotozoários/química , HumanosRESUMO
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.
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Ensaios de Triagem em Larga Escala , Bibliotecas de Moléculas Pequenas , Humanos , Bibliotecas de Moléculas Pequenas/farmacologia , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Escherichia coli , Farmacorresistência Bacteriana MúltiplaRESUMO
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.
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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.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Células Estreladas do Fígado/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Microambiente Tumoral , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Cirrose Hepática/induzido quimicamenteRESUMO
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.
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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.
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Neoplasias Encefálicas , Telemedicina , Humanos , Análise Custo-Benefício , Qualidade de Vida , Custos de Cuidados de Saúde , Neoplasias Encefálicas/terapia , Anos de Vida Ajustados por Qualidade de VidaRESUMO
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.
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Lesões Encefálicas Traumáticas , Memória Episódica , Humanos , Lesões Encefálicas Traumáticas/psicologia , Lesões Encefálicas Traumáticas/reabilitação , Cognição , Aprendizagem , Transtornos da Memória , Resultado do Tratamento , Ensaios Clínicos como AssuntoRESUMO
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.
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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.
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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.
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Transtorno do Deficit de Atenção com Hiperatividade , Função Executiva , Criança , Humanos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Memória de Curto PrazoRESUMO
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.
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Neoplasias Encefálicas , Glioma , Telemedicina , Adulto , Humanos , Qualidade de Vida , Neoplasias Encefálicas/terapia , Cuidadores/psicologia , Depressão/terapiaRESUMO
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.
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COVID-19 , Minorias Étnicas e Raciais , Disparidades nos Níveis de Saúde , Estigma Social , Feminino , Humanos , Masculino , População do Leste Asiático , Etnicidade , Grupos Minoritários , Pandemias , Hong KongRESUMO
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.
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COVID-19 , Adolescente , Criança , Humanos , Adaptação Psicológica , Ansiedade , Austrália , Fatores de Risco , Masculino , FemininoRESUMO
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.
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Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Doença de Chagas/tratamento farmacológico , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Relação Estrutura-Atividade , Tripanossomicidas/uso terapêutico , Tripanossomicidas/farmacocinéticaRESUMO
Prospective memory (PM), which enables one to remember to carry out delayed intentions, is crucial for everyday functioning. PM commonly deteriorates upon cognitive decline in older adults, but several studies have shown that PM in older adults can be improved by training. The current study aimed to summarise this evidence by conducting a qualitative systematic analysis and quantitative meta-analysis of the effects of PM training in older adults, for which systematic searches were conducted across seven databases (Cochrane Library, Embase, PubMed, PsycInfo, Web of Science, CINAHL and Scopus). Forty-eight studies were included in the qualitative analysis, and 43% of the assessed PM training interventions showed positive gains in enhancing PM. However, the methodological quality varied across the studies, with 41% of the non-randomised control trials (non-RCTs) rated as having either serious or critical risk of bias. Therefore, only 29 RCTs were included in the subsequent quantitative meta-analysis. We found a significant and moderate immediate efficacy (Hedges' g = 0.54) of PM training in enhancing PM performance in older adults, but no significant long-term efficacy (Hedges' g = 0.20). Two subgroup analyses also revealed a robust training efficacy across the study population (i.e., healthy and clinical population) and the number of training sessions (i.e., single session and programme-based). Overall, this study provided positive evidence to support PM training in older adults. Further studies are warranted to explore the mechanisms by which PM training exerts its effects, and better-quality RCTs are needed to provide more robust evidence supporting our findings.
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Disfunção Cognitiva , Memória Episódica , Humanos , Idoso , Treino Cognitivo , CogniçãoRESUMO
OBJECTIVES: Health practitioners' understanding of the impact of age-based stereotype threat (ABST) on the cognitive test performance of older adults is not well understood. This study aimed to investigate health practitioners' ability to recognize the influence of ABST in the cognitive assessment of older adults and their perceptions of its impact in practice. METHODS: One-hundred and twenty-nine health practitioners (86% female; M age = 39.75, SD = 11.50) with experience in conducting cognitive assessments with older adults (mainly psychologists and occupational therapists) completed an online survey assessing demographic and practice characteristics, aging beliefs, a hypothetical cognitive assessment scenario, and perceived impact of ABST on practice. RESULTS: Overall, health practitioners rated ABST factors in the assessment scenario as less detrimental to cognitive performance than internal and external factors. In a hierarchical regression model, lower recognition of ABST and negative aging beliefs significantly accounted for lower perceived impact of ABST on older adults' cognitive test performance in practice (R2 = .37, p < .001). CONCLUSION: Health practitioners may not recognize the influence of ABST on assessment findings, especially if they hold negative aging beliefs. The findings highlight the need to improve health practitioners' knowledge of ABST to increase the validity of cognitive testing in older adults.
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Envelhecimento , Estereotipagem , Humanos , Feminino , Idoso , Masculino , Envelhecimento/psicologia , Fatores Etários , Inquéritos e Questionários , CogniçãoRESUMO
Prospective Memory (PM), the ability to remember to carry out intentions in the future, is often impaired after stroke. Little is known about rehabilitation of PM post-stroke with literature limited by small sample sizes and reliance on self-reported memory performance. Implementation intentions may make prospective remembering more automatic and follow a simple if-then structure (if X occurs, then I will do Y), focusing on the cue rather than the task. We aimed to investigate the effect of implementation intentions on PM post-stroke. Twenty-eight individuals with stroke and 27 controls were randomly allocated to a standard instruction or implementation intention condition and completed an assessment battery over two sessions. Implementation intention instructions were provided for PM tasks on the Delayed Message Task, Lexical Decision Prospective Memory Task (LDPMT), and the Virtual Reality Prospective Memory Shopping Task. The implementation intention groups performed better on all PM tasks compared to the standard instruction group, but no results reached statistical significance, likely due to the small sample size. In addition, the implementation intentions group monitored the time significantly more on the LDPMT than those in the standard instruction group.