Epidemiology and genetic diversity of Burkholderia pseudomallei from Riau Province, Indonesia.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, that is common in tropical and subtropical countries including Southeast Asia and Northern Australia. The magnitude of undiagnosed and untreated melioidosis across the country remains unclear. Given its proximity to regions with high infection rates, Riau Province on Sumatera Island is anticipated to have endemic melioidosis. This study reports retrospectively collected data on 68 culture-confirmed melioidosis cases from two hospitals in Riau Province between January 1, 2009, and December 31, 2021, with full clinical data available on 41 cases. We also describe whole genome sequencing and genotypic analysis of six isolates of B. pseudomallei. The mean age of the melioidosis patients was 49.1 (SD 11.5) years, 85% were male and the most common risk factor was diabetes mellitus (78%). Pulmonary infection was the most common presentation (39%), and overall mortality was 41%. Lung as a focal infection (aOR: 6.43; 95% CI: 1.13-36.59, p = 0.036) and bacteremia (aOR: 15.21; 95% CI: 2.59-89.31, p = 0.003) were significantly associated with death. Multilocus sequence typing analysis conducted on six B.pseudomallei genomes identified three sequence types (STs), namely novel ST1794 (n = 3), ST46 (n = 2), and ST289 (n = 1). A phylogenetic tree of Riau B. pseudomallei whole genome sequences with a global dataset of genomes clearly distinguished the genomes of B. pseudomallei in Indonesia from the ancestral Australian clade and classified them within the Asian clade. This study expands the known presence of B. pseudomallei within Indonesia and confirms that Indonesian B. pseudomallei are genetically linked to those in the rest of Southeast Asia. It is anticipated that melioidosis will be found in other locations across Indonesia as laboratory capacities improve and standardized protocols for detecting and confirming suspected cases of melioidosis are more widely implemented.

Implementing a clinical scientist-led screening clinic for hypertrophic and dilated cardiomyopathies.

BACKGROUND: The burden of screening for inherited cardiac conditions on health services grows ever larger, with each new diagnosis necessitating screening of additional family members. Screening these usually asymptomatic, low-risk individuals is currently performed by consultant cardiologists, consuming vital clinic resources that could otherwise be diverted to sicker patients requiring specialist consultant input. Clinical scientists now constitute a highly skilled and often underutilised group of individuals with training in areas such as clinical evaluation, 12-lead electrocardiography (ECG) interpretation, and echocardiography. These skills place them in a unique position to offer a full screening evaluation in a single consultation. The aim of this study was to implement and evaluate a novel clinical scientist-led screening clinic for first-degree relatives of patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The clinical scientist-led screening clinic was established at a London tertiary centre to allow review of asymptomatic, first-degree relatives of patients with a confirmed diagnosis of HCM or DCM, independent of a cardiology consultant. Patients were evaluated with history, examination, ECG, and echocardiography, with further investigations if deemed necessary. A retrospective review was performed of the first 200 patients seen in the clinic. RESULTS: Of the 200 individuals reviewed between September 2019 and July 2022, 99 had a proband with HCM and 101 a proband with DCM. Overall, 169 individuals (85%) revealed normal screenings and were discharged. Thirty-one individuals (15.5%), all asymptomatic, revealed ECG changes and/or significant echocardiographic findings. Of these, 21 individuals (10.5% of the total cohort) were subsequently diagnosed with a cardiomyopathy or early phenotypic changes consistent with a cardiomyopathy (11 with HCM and 10 with DCM). These individuals were referred on to an inherited cardiac conditions consultant clinic for regular follow-up. Overall, 179 consultant clinic appointments were saved which could instead be allocated to patients requiring specialist consultant input. CONCLUSIONS: This is the first description of a clinical scientist-led screening clinic for first-degree relatives of patients with HCM and DCM. The findings demonstrate that implementation of such a service into routine clinical practice is feasible, effective, safe, and can free up capacity in consultant clinics for patients requiring specialist input.

Age of Alzheimer's disease diagnosis in people with Down syndrome and associated factors: Results from the Horizon 21 European Down syndrome consortium.

INTRODUCTION: People with Down syndrome (DS) have high risk of developing Alzheimer's disease (AD). This study examined mean ages of AD diagnosis and associations with co-occurring conditions among adults with DS from five European countries. METHODS: Data from 1335 people with DS from the Horizon 21 European DS Consortium were used for the analysis. RESULTS: Mean ages of AD diagnosis ranged between 51.4 (SD 7.0) years (United Kingdom) and 55.6 (SD 6.8) years (France). Sleep-related and mental health problems were associated with earlier age of AD diagnosis. The higher number of co-occurring conditions the more likely the person with DS is diagnosed with AD at an earlier age. DISCUSSION: Mean age of AD diagnosis in DS was relatively consistent across countries. However, co-occurring conditions varied and impacted on age of diagnosis, suggesting that improvements can be made in diagnosing and managing these conditions to delay onset of AD in DS. HIGHLIGHTS: Mean age of AD diagnosis was relatively consistent between countries Sleep problems and mental health problems were associated with earlier age of AD diagnosis APOE ε4 carriers were diagnosed with AD at an earlier age compared to non-carriers Number of co-occurring conditions was associated with earlier age of AD diagnosis No differences between level of intellectual disability and mean age of AD diagnosis.

Positive communication workshops: are they useful for treatment programmes for anorexia nervosa?

Background: Social isolation, loneliness and difficulties in relationships are often described as a core feature of eating disorders. Based on the experimental research, we have designed one-off workshops for patients in inpatients and day care services and evaluated its acceptability and effectiveness using feedback questionnaires. Methods: This naturalistic project is an evaluation of multiple positive communication workshops. Forty-one participants completed workshop questionnaires, which were provided immediately at the beginning and end of the workshop, including feedback on these one-off groups. The workshops consisted of educational and experiential components. The questionnaire outcomes were evaluated by independent researchers. Results: All participants were female adults with a mean age of 33 (12.2) and a diagnosis of Anorexia Nervosa (AN; either restrictive or binge-purge subtype). Post-workshop questionnaires showed large effect sizes in the improvement of understanding the importance and confidence in using positive communication strategies. Discussion: Addressing social communication difficulties in eating disorder treatment programmes adds valuable dimensions to these symptom-based treatments in both inpatient settings and day services, and may provide broader benefits in overall social functioning in patients with AN. Conclusion: Brief one-off workshops targeting social functioning for patients with eating disorders might be useful complementary input for treatment programmes.

The acceptability of homebased exercise snacking and Tai-chi snacking amongst high and low function UK and Taiwanese older adults.

Introduction: Exercise "snacking" and Tai-chi 'snacking' protocols are designed to overcome typical barriers to older adults' participation in muscle strength and balance exercise, using short bouts of home-based exercise. This study aimed to investigate the acceptability of homebred exercise- and Tai-chi snacking in British and Taiwanese older adults of high and low physical function. Methods: Thirty-three British and Thirty Taiwanese older adults took part in semi-structured interviews, after trying 1-week of exercise- and Tai-chi snacking. The interview schedule and deductive framework analysis was based on the seven components of the Theoretical Framework of Acceptability (TFA). Differences between the Taiwanese and United Kingdom participants and those considered high versus low physical function were also analysed. Results: Both snacking regimes were found to be convenient and easy to implement. Participants reported that no activity had to be given up, and considered the programmes would be beneficial to their physical and mental health. Interestingly, more UK-based participants preferred the elegant and relaxing movements of Tai-chi snacking, yet participants with low physical function experienced difficulties when mastering Tai-chi movements. A few high physical function participants perceived exercise snacking to be tedious. Discussion: Overall, the snacking exercise was found to be acceptable and useful. Personal affective attitude and different cultural backgrounds may affect exercise participation. Nevertheless, it is important to consider individuals' physical function when designing exercise regime. The findings indicate that making Tai-chi snacking easier to master initially, building in progression and adding some upper body movements in the exercise snacking may further enhance acceptability.

Melioidosis in Timor-Leste: First Case Description and Phylogenetic Analysis.

Burkholderia pseudomallei, the causative agent of melioidosis, has not yet been reported in Timor-Leste, a sovereign state northwest of Australia. In the context of improved access to diagnostic resources and expanding clinical networks in the Australasian region, we report the first 3 cases of culture-confirmed melioidosis in Timor-Leste. These cases describe a broad range of typical presentations, including sepsis, pneumonia, multifocal abscesses, and cutaneous infection. Phylogenetic analysis revealed that the Timor-Leste isolates belong to the Australasian clade of B. pseudomallei, rather than the Asian clade, consistent with the phylogeographic separation across the Wallace Line. This study underscores an urgent need to increase awareness of this pathogen in Timor-Leste and establish diagnostic laboratories with improved culture capacity in regional hospitals. Clinical suspicion should prompt appropriate sampling and communication with laboratory staff to target diagnostic testing. Local antimicrobial guidelines have recently been revised to include recommendations for empiric treatment of severe sepsis.

In-person and online sensory wellbeing workshop for eating disorders: updated case series.

BACKGROUND: A one-off sensory wellbeing workshop has been developed to help patients with eating disorders (ED) manage sensory sensitivities. The aim of this study was to evaluate and compare the outcomes of the workshop in online versus face-to-face (F2F) formats among a sample of patients with ED. METHODS: Cumulative link models were applied to the outcome measures (awareness of sensory wellbeing, awareness of strategies to enhance sensory wellbeing, and confidence in managing sensory wellbeing) to test the differences between online and F2F workshops. Participants' ratings of usefulness of the workshop were also compared between online and F2F workshops. RESULTS: A total of 14 workshops (4 online and 10 F2F) were run from 2020 to 2023. All participants reported significant and substantial improvements in all outcome measures. There was no significant difference in outcomes between online and F2F workshops. The majority of patients rated the workshops as useful. CONCLUSIONS: Both online and face-to-face formats of the sensory workshop led to improvement in sensory wellbeing management for patients with ED. Future studies are warranted to test the impact of the workshop on ED treatment outcomes.

People with eating disorders often have sensory issues, which can include being too sensitive to some senses (hearing, smell or taste, for example) or not sensitive enough. Explaining how the sensory system works and developing helpful strategies to manage sensory difficulties could be beneficial in the process of therapy. To try and support this, clinicians and researchers designed a sensory wellbeing workshop to help people become more aware of their sensory wellbeing and teach them strategies to manage their sensory wellbeing. The workshop can be delivered online or face-to-face. This study examined the feedback for online and face-to-face workshops. We found that both formats were helpful for people with eating disorders. We also discuss possible ways to develop and test the workshop further in order to better support patients with sensory difficulties.

Analysis of symptom clusters amongst adults with anorexia nervosa: Key severity indicators.

This study used cluster analysis to explore clinically relevant subgroups of adult patients with anorexia nervosa (AN). Patients were clustered based on their body mass index (BMI), eating disorder symptomatology, anxiety and depression symptoms and autistic characteristics. The difference between clusters in work and social functioning, duration of illness, bingeing and purging behaviour, previous hospitalisations and number of comorbidities was also investigated. Two meaningful clusters emerged: a higher symptoms cluster with more severe eating pathology, anxiety, depression, and more autistic traits, and a second cluster with lower symptoms. BMI did not make major contributions to cluster formation. The higher symptoms cluster also reported lower self-efficacy to change, more previous hospitalisations, comorbid diagnoses, binge eating and purging behaviours and use of psychotropic medication. Our findings suggest that weight alone may not be a significant severity indicator amongst inpatients with AN, and targeted treatment of AN should consider a broader range of symptom severity indicators.

Exploring Cefiderocol Resistance Mechanisms in Burkholderia pseudomallei.

Cefiderocol is a siderophore cephalosporin designed mainly for treatment of infections caused by ß-lactam and multidrug-resistant Gram-negative bacteria. Burkholderia pseudomallei clinical isolates are usually highly cefiderocol susceptible, with in vitro resistance found in a few isolates. Resistance in clinical B. pseudomallei isolates from Australia is caused by a hitherto uncharacterized mechanism. We show that, like in other Gram-negatives, the PiuA outer membrane receptor plays a major role in cefiderocol nonsusceptibility in isolates from Malaysia.

B-box1 Domain of MID1 Interacts with the Ube2D1 E2 Enzyme Differently Than RING E3 Ligases.

The MID1 TRIM protein is important for ventral midline development in vertebrates, and mutations of its B-box1 domain result in several birth defects. The B-box1 domain of the human MID1 protein binds two zinc atoms and adopt a similar ßßα-RING structure. This domain is required for the efficient ubiquitination of protein phosphatase 2A, alpha4, and fused kinase. Considering the structural similarity, the MID1 B-box1 domain exhibits mono-autoubiquitination activity, in contrast to poly-autoubiquitination observed for RING E3 ligases. To understand its mechanism of action, the interaction of the B-box1 domain with Ube2D1 (UbcH5a, E2), a preferred E2 ligase, is investigated. Using isothermal titration calorimetry, the MID1 RING and B-box1 domains were observed to have similar binding affinities with the Ube2D1 protein. However, NMR 15N-1H Heteronuclear Single Quantum Coherence titration, 15N relaxation data, and High Ambiguity Driven protein-protein DOCKing (HADDOCK) calculations show the B-box1 domain binding on a surface distinct from where RING domains bind. The novel binding interaction shows the B-box1 domain partially overlapping the noncovalent Ube2D1 and a ubiquitin binding site that is necessary for poly-autoubiquitination activity. The B-box1 domain also displaces the ubiquitin from the Ube2D1 protein. These studies reveal a novel binding interaction between the zinc-binding ßßα-fold B-box1 domain and the Ube2D enzyme family and that this difference in binding, compared to RING E3 ligases, provides a rationale for its auto-monoubiquitination E3 ligase activity.

A conserved active site PenA ß-lactamase Ambler motif specific for Burkholderia pseudomallei/B. mallei is likely responsible for intrinsic amoxicillin-clavulanic acid sensitivity and facilitates a simple diagnostic PCR assay for melioidosis.

Burkholderia pseudomallei is a soil- and water-dwelling Gram-negative bacterium that causes melioidosis in humans and animals. Amoxicillin-clavulanic acid (AMC) susceptibility has been hailed as an integral part of the screening algorithm for identification of B. pseudomallei, but the molecular basis for the inherent AMC susceptibility of this bacterium remains undefined. This study showed that B. pseudomallei (and the closely-related B. mallei) wild-type strains are the only Burkholderia spp. that contain a 70STSK73 PenA Ambler motif. This motif was present in >99.5% of 1820 analysed B. pseudomallei strains and 100% of 83 analysed B. mallei strains, and is proposed as the likely cause for their inherent AMC sensitivity. The authors developed a polymerase chain reaction (PCR) assay that specifically amplifies the penA70ST(S/F)K73-containing region from B. pseudomallei and B. mallei, but not from the remaining B. pseudomallei complex species or the 70STFK73 region from the closely-related penB of B. cepacia complex species. The abundance and purity of the 193-bp PCR fragment from putative B. pseudomallei isolates from clinical and environmental samples is likely sufficient for reliable confirmation of the presence of B. pseudomallei. The PCR assay is designed to be especially suited for use in resource-constrained areas. While not further explored in this study, the assay may allow diagnosis of putative B. mallei in culture isolates from animal and human samples.

Evaluation of the impact of the addition of a heart failure prescribing pharmacist to consultant-led heart failure ward round at a tertiary hospital.

OBJECTIVE: Pharmacists attending general medical post-admission ward rounds is established good practice. However, there is a lack of evidence on the impact of specialist heart failure (HF) prescribing pharmacists on consultant HF ward rounds. The aim of this study was to evaluate the impact on prescribing when a specialist HF prescribing pharmacist attended inpatient HF ward rounds. METHODS: A prospective service evaluation completed at a tertiary hospital between September and December 2020. The same HF prescribing pharmacist attended the HF consultant-led ward round once a week on 15 occasions. For each medicine change, the pharmacist documented: who suggested the intervention, the medicine, prescribing action, reason for review and the primary reason for change. Medicines were categorised into four groups (heart failure, cardiovascular, anticoagulation and other) for analysis. RESULTS: A total of 158 patients were reviewed and 226 individual changes suggested; 48% of these were consultant led (n=108) and 52% (n=118) due to pharmacist recommendations. All medicines interventions were prescribed on the round by the pharmacist. For consultants, the primary reason for medicine change was to ensure efficacy of HF medicines, 80% (n=73), followed by safety (HF medicines), 20% (n=18). For the pharmacist, the primary reason was safety across all the medicine groups, 36% (n=42), followed by efficacy relating to missing drug history items, 24% (n=28). CONCLUSIONS: HF consultants focused on ensuring patients have the most effective combination of HF medications. The addition of a specialist HF prescribing pharmacist ensured a wider range of medicines were reviewed for safety and optimisation, helping to deliver a holistic review of all medications.

Barriers to physical activity for father's living in marginalising conditions.

Physical activity can be a conduit for improving men's social connectedness as well as physical gains for well-being. However, marginalised men, and fathers in particular, can be challenged to engage in leisure time physical activity. This qualitative study reports how fathers, who experience complex and significant social and health inequities, conceptualise and experience barriers to physical activity. Drawing from focus groups with 17 fathers, and semi-structured interviews with seven service providers about their perspectives on men's physical activity in Vancouver's Downtown Eastside (DTES), a highly marginalised neighbourhood. A masculinities framework was used to describe and contextualise physical activity in fathers' lives. Three themes were inductively derived through the analyses: (1) 'they're busy surviving' a finding referencing the work and limits invoked by poverty wherein survival was triaged ahead of leisure time physical activity; (2) 'there is no activity centre' chronicling the lack of physical activity spaces, programmes and resources available to fathers; and (3) 'lifestyle affects our capability to exercise' a theme detailing how social isolation amplified by factors including housing and opioid crises, and being a father in a resource poor setting imposed significant barriers to physical activity. The findings support reconceptualising physical activity programmes with men who are living in marginalising conditions to address behavioural and structural health inequities in tailoring father-centred programmes and resources.

Absent and Problematic: The Representation of Fathers in the Program Policies of Organizations that Provide Family-Centred Services in Vancouver's Downtown Eastside.

Parenting education interventions and parenting programs are important for health promotion efforts among children and families; however, the majority of parenting programs are directed towards and attended by mothers. This is problematic because research has consistently demonstrated that fathers' active participation in the family can have a positive influence on mothers' well-being, children's self-esteem, success in school, and interpersonal relationships. In this paper, using an intersectional poststructuralist framework, document analysis, and Bacchi and Goodwin's "What's the problem represented to be" approach (WPR), we analyzed the program policies of 12 organizations that provide family-centred services in the Downtown Eastside of Vancouver, British Columbia, Canada. We identified the following three discourses: organizations strive to be client-centred and provide choices; organizations want to empower their participants; and women need safe place to raise their families. Our analysis revealed that fathers are absent or represented as problems in program policies, and that this has consequences for not only fathers but also mothers and children.

Taking Practical Steps: A Feminist Participatory Approach to Cocreating a Trauma- and Violence-Informed Physical Activity Program for Women.

Trauma- and violence-informed physical activity (TVIPA) is a feasible approach to improve access/engagement in physical activity for pregnant/parenting women with experiences of trauma. Through feminist participatory action research, 56 semistructured interviews were completed to understand TVIPA. Four themes were identified: (1) "I have to be on edge": Trauma and violence pervade women's lives, (2) "It should be mandatory that you feel safe": Emotional safety is essential, (3) "The opportunity to step up and be decision-makers and leaders": Choice, collaboration, and connection create safety, and (4) "It's a good start for healing," strengths-based and capacity building foster individual and community growth.

Amyloid- ß and tau deposition influences cognitive and functional decline in Down syndrome.

This study investigates whether tau has (i) an independent effect from amyloid-ß on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-ß in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [18F]-AV1451 and PET [11C]PiB scans to quantify tau deposition in Braak regions II-VI and the Striatum and amyloid-ß status respectively. Linear Mixed Effects models were implemented to assess how tau and amyloid-ß deposition are related to change over three time points. Tau was a significant independent predictor of cognitive and functional change. The three-way interaction between time, [11C]PiB status and tau was significant in the models of episodic memory and visuospatial cognition. Baseline tau is a significant predictor of cognitive and functional decline, over and above the effect of amyloid-ß status. Results suggest a synergistic relationship between amyloid-ß status and tau as predictors of change in memory and visuospatial cognition.

A description of virtual skills workshops for supporters of loved ones with eating disorders: Indicators of benefit and acceptability, clinical reflections and consideration of neurodiversity.

OBJECTIVE: Providing information and support to those supporting a loved one with an eating disorder is a key part of evidence-based service provision. We report on how we took our workshops for supporters online during the Covid-19 Pandemic when country-side physical distancing restrictions meant we were unable to work face to face. METHODS: We outline the structure of an eight-session 2-h workshop series delivered fortnightly facilitated by a multidisciplinary team of clinicians, researchers and experts by experience. We use a repeated-measures design to understand the possible benefits of the workshops on supporter skills (n = 76). RESULTS: Measured using the Caregiver Skills Scale, we observed small-sized improvements in the overall skills (D = 0.43) of n = 17 supporters who provided data at the end of the intervention. Supporters gave largely positive feedback on the virtual format. They particularly liked the opportunity to interact with other supporters. As facilitators, we overcome our initial anxiety around workshop delivery using a new platform and reflected that having more time to cover key information and for skills practice over a period of 16 weeks offered opportunities to develop and reflect on new skill together as a group. We were also able to work with larger groups of supporters, as several barriers to access were removed. CONCLUSIONS: As the workshops reached a larger number of supporters than through face to face delivery and were of benefit to those who reported on their skills, we plan to continue offering workshops to supporters online in future.