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.

Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs.

DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs.

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.

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.

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.

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.

Prospective Memory Training in Older Adults: A Systematic Review and Meta-Analysis.

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.

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.

Health practitioner beliefs regarding the impact of age-based stereotype threat on performance in the cognitive assessment of older adults.

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.

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.

The impact of using implementation intentions as task instructions on prospective memory performance after stroke.

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.

Madurastatins with Imidazolidinone Rings: Natural Products or Side-Reaction Products from Extraction Solvents?

Madurastatins are a group of pentapeptides containing an oxazoline moiety, and, in a few cases, an imidazolidinone ring as an additional structural feature. In our search for new potential antiparasitic metabolites from natural sources, we studied the acetone extracts from a culture of Actinomadura sp. CA-135719. The LC/HRMS analysis of this extract identified the presence of the known madurastatins C1 (1), D1 (4), and D2 (5) together with additional members of the family that were identified as the new madurastatins H2 (2) and 33-epi-D1 (3) after isolation and spectroscopic analysis. The planar structures of the new compounds were established by HRMS, ESI-qTOF-MS/MS, and 1D and 2D NMR data, and their absolute configuration was proposed using Marfey's and bioinformatic analyses of the biosynthetic gene cluster (BGC). A revision of the absolute configuration of madurastatins D1 and D2 is proposed. Additionally, madurastatins containing imidazolidinone rings are proved to be artifacts originating during acetone extraction of the bacterial cultures.

Immune Responses to the ChAdOx1 nCoV-19 and BNT162b2 Vaccines and to Natural Coronavirus Disease 2019 Infections Over a 3-Month Period.

BACKGROUND: There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections. METHOD: We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses. RESULTS: A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1. CONCLUSIONS: Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.

Discovery of novel Leishmania major trypanothione synthetase inhibitors by high-throughput screening.

Leishmaniasis is an infectious disease caused by obligate intracellular protozoa of the genus Leishmania with high infection and death rates in developing countries. New drugs with better pharmacological performance with regards to safety, efficacy, toxicity, and drug resistance than those/the ones currently used are urgently needed. Trypanothione synthetase (TryS) is an attractive target for the development of drugs against leishmaniasis because it is specific and essential to kinetoplastid parasites. In this study, Leishmaniamajor TryS was expressed and purified, and the kinetic parameters of purified TryS were determined. To identify novel inhibitors of LmTryS, a high-throughput screening (HTS) assay was developed and used to screen a library of 35,040 compounds. In the confirmatory assay, 42 compounds displayed half maximal inhibitory concentration (IC50) values < 50 µM and six of them corresponded to novel structures with IC50 ranging from 9 to 19 µM against LmTryS enzyme activity. Of the six inhibitors, TS001 showed the highest activity against growth of L. major promastigotes, L. donovani promastigotes, and Trypanosoma brucei brucei Lister 427 with IC50 values of 17, 26, and 31 µM, respectively. An in silico docking study using a homology model of LmTryS predicted the molecular interactions between LmTryS and the inhibitors.

COVID-19 one year on: identification of at-risk groups for psychological trauma and poor health-protective behaviour using a telephone survey.

BACKGROUND: This study examined the profiles and correlates of psychological trauma, compliance with preventative measures, vaccine acceptance and participation in voluntary testing during the novel coronavirus disease 2019 (COVID-19) pandemic among the adult population in Hong Kong (n = 3,011). METHODS: Data were collected through a telephone survey between December 2020 and February 2021, using measures of psychological trauma, compliance with preventative measures, reading news reports on COVID-19, vaccine acceptance and willingness to participate in voluntary testing. RESULTS: The prevalence of possible post-traumatic stress disorder was found to be 12.4%. Respondents were generally compliant with routine preventative measures, and approximately half had accepted vaccination and voluntary testing. Participants who had lower levels of education, were unemployed or had no income showed greater psychological trauma symptoms, whereas female, older and more educated participants showed greater compliance with preventative measures. Participants who spent more time watching news reports of COVID-19 had greater psychological trauma, but also greater compliance. Participants who were male, older, had lower education levels or were married showed greater acceptance of vaccination and participation in voluntary testing. CONCLUSIONS: Socio-demographic factors affected both psychological trauma and engagement in health-protective measures at one year after the onset of the pandemic. The theoretical and practical implications of these findings are discussed.

Strategies to build more effective interventions for elder abuse: a focus group study of nursing and social work professionals in Hong Kong.

BACKGROUND: One in six older adults living in communities experience abuse and neglect. Elder abuse has serious consequences for individuals, families, and society, including mortality, physical and psychological morbidities, and increased care requirements. Timely and effective interventions for elder abuse should therefore be a priority. This study used a qualitative focus group approach to address the following questions: What are the essential elements of elder abuse interventions? What can be done to improve current interventions? METHOD: The 32 participants in this focus group study included social workers, medical social workers, and nurses from seven organizations who shared their knowledge and insights. All sessions were conducted online, audio-recorded, and transcribed verbatim. Three researchers with backgrounds in social work and psychology independently coded the transcripts and agreed on the themes emerging from the focus groups. RESULTS: Based on the experiences of frontline helping professionals in Hong Kong, we highlighted the key factors for effective elder abuse intervention: 1) identification and assessment; 2) essential skills and attitudes; 3) elements of effective interventions; 4) collaborative efforts across disciplines and agencies; and 5) raising awareness among professionals and the public. CONCLUSIONS: Training can equip frontline professionals with the necessary skills to identify elder abuse cases and to assess the risk of abuse. Effective interventions should not only address clients' safety and need for tangible support but also respect their autonomy and privacy. A client-centered, strength-based approach that involves supportive peers and addresses the complex family relationships involved can be useful. Interventions should also involve cross-discipline and cross-agency collaboration.

Perceptions of and hesitancy toward COVID-19 vaccination in older Chinese adults in Hong Kong: a qualitative study.

BACKGROUND: COVID-19 vaccination is recommended for older adults by the World Health Organization. However, by July 15, 2021, only 26% of individuals over 60 years old in Hong Kong had received a first dose of the vaccine. The health belief model and the theory of planned behavior have been used to understand the determinants for COVID-19 vaccination in past literature. However, vaccination determinants can be complex and involve social and cultural factors that cannot be explained by micro-individual factors alone; hence, the health belief model and the theory of planned behavior cannot provide a complete understanding of vaccine hesitancy. Few studies on the barriers to, hesitancy toward, and motivations for COVID-19 vaccination among older Chinese adults have been performed. The aim of this study is to fill this gap by conducting a comprehensive analysis of this subject using the critical medical anthropology framework, extending the health belief model and the theory of planned behavior in understanding vaccination determinants among the older adult population. METHODS: Between November 2020 and February 2021, 31 adults (24 women and 7 men) over the age of 65 took part in semi-structured, one-on-one interviews. The data we gathered were then analyzed through a phenomenological approach. RESULTS: Two major themes in the data were examined: barriers to vaccination and motivations for vaccination. The participants' perceptions of and hesitancy toward vaccination demonstrated a confluence of factors at the individual (trust, confidence, and social support networks), microsocial (stigma toward health care workers), intermediate-social (government), and macrosocial (cultural stereotypes, civic and collective responsibility, and economic considerations) levels according to the critical medical anthropology framework. CONCLUSIONS: The decision to receive a COVID-19 vaccination is a complex consideration for older adults of low socioeconomic status in Hong Kong. Using the critical medical anthropology framework, the decision-making experience is a reflection of the interaction of factors at different layers of social levels. The findings of this study extend the health belief model and the theory of planned behavior regarding the understanding of vaccination perceptions and relevant behaviors in an older adult population.

Drug-like molecules with anti-trypanothione synthetase activity identified by high throughput screening.

Trypanothione synthetase (TryS) catalyses the synthesis of N1,N8-bis(glutathionyl)spermidine (trypanothione), which is the main low molecular mass thiol supporting several redox functions in trypanosomatids. TryS attracts attention as molecular target for drug development against pathogens causing severe and fatal diseases in mammals. A drug discovery campaign aimed to identify and characterise new inhibitors of TryS with promising biological activity was conducted. A large compound library (n = 51,624), most of them bearing drug-like properties, was primarily screened against TryS from Trypanosoma brucei (TbTryS). With a true-hit rate of 0.056%, several of the TbTryS hits (IC50 from 1.2 to 36 µM) also targeted the homologue enzyme from Leishmania infantum and Trypanosoma cruzi (IC50 values from 2.6 to 40 µM). Calmidazolium chloride and Ebselen stand out for their multi-species anti-TryS activity at low µM concentrations (IC50 from 2.6 to 13.8 µM). The moieties carboxy piperidine amide and amide methyl thiazole phenyl were identified as novel TbTryS inhibitor scaffolds. Several of the TryS hits presented one-digit µM EC50 against T. cruzi and L. donovani amastigotes but proved cytotoxic against the human osteosarcoma and macrophage host cells (selectivity index ≤ 3). In contrast, seven hits showed a significantly higher selectivity against T. b. brucei (selectivity index from 11 to 182). Non-invasive redox assays confirmed that Ebselen, a multi-TryS inhibitor, induces an intracellular oxidative milieu in bloodstream T. b. brucei. Kinetic and mass spectrometry analysis revealed that Ebselen is a slow-binding inhibitor that modifies irreversible a highly conserved cysteine residue from the TryS's synthetase domain. The most potent TbTryS inhibitor (a singleton containing an adamantine moiety) exerted a non-covalent, non-competitive (with any of the substrates) inhibition of the enzyme. These data feed the drug discovery pipeline for trypanosomatids with novel and valuable information on chemical entities with drug potential.

Improving self-awareness of prospective memory function after TBI using experiential feedback on a board game activity: An observational study.

This study investigated whether experiential and video feedback on performance of prospective memory (PM) tasks embedded within a board game activity improved self-awareness of PM function in adults with moderate-severe traumatic brain injury. An observational pre-post study design with 26 participants from a larger trial of a 6-session PM rehabilitation programme. Sessions 3 and 4 included a board game activity with embedded time-, event-, and activity-based PM tasks. Verbal feedback was provided by therapists during the game and video feedback afterwards. Self-ratings of performance were used to divide the sample into under-estimators (n = 7), accurate estimators (n = 9) and over-estimators (n = 10) of actual PM performance. The discrepancy between self- and therapist ratings of PM performance was measured before and after the game, and following video feedback, and compared between timepoints using non-parametric statistics. Post-task self-evaluations were more accurate than pre-task self-evaluations for the under- and over-estimator groups. Under-estimators showed significant improvement in accuracy of ratings for activity-based PM. Over-estimators showed improvement for event-based PM. Further improvements after video feedback were not significant. The board game activity provided a vehicle for experiential feedback and a means of engaging both those with impaired self-awareness and heightened self-awareness of PM in cognitive rehabilitation.

Measuring domain-specific deficits in self-awareness in children and adolescents with acquired brain injury: Component analysis of the Paediatric Awareness Questionnaire.

Self-awareness has been found to vary across different functional domains for adults with acquired brain injury (ABI); however, domain-specific self-awareness is yet to be investigated following paediatric ABI. This study aimed to validate the Paediatric Awareness Questionnaire (PAQ) as a multi-domain measure of self-awareness and to investigate domain-specific self-awareness in children with ABI. One hundred and ninety-seven children and adolescents (8-16 years, M = 12.44, SD = 2.62) with mixed causes of ABI (70% with traumatic brain injury) and their parents (n = 197) were recruited through consecutive rehabilitation appointments and completed the PAQ. The 37 items of the parent version of the PAQ were subjected to a principal component analysis with varimax rotation. A five-component solution (29 items) explained 64% of the variance in the PAQ items. Components revealed five domains of self-awareness: socio-emotional functioning, activities of daily living (ADLs), cognition, physical functioning, and communication. Internal consistency of the components ranged from acceptable to excellent (α = .70-.95). The analysis identified that children had poorer self-awareness of cognitive functioning than socio-emotional functioning, ADLs, and communication skills. Overall, the findings identify five components (i.e., functional domains) of self-awareness and provide some support that self-awareness varies across domains following paediatric ABI.