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Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo
No full textThis study investigated preventative and therapeutic agents against human T cell lymphotropic virus type-1 subtype-C (HTLV-1c) infection. We established and characterized a humanized mouse model of HTLV-1c infection and identified that HTLV-1c disease appears slightly more aggressive than the prevalent HTLV-1 subtype-A (HTLV-1a), which may underpin increased risk for infection-associated pulmonary complications in HTLV-1c. Combination antiretroviral therapy with tenofovir and dolutegravir at clinically relevant doses significantly reduced HTLV-1c transmission and disease progression in vivo. Single-cell RNA sequencing (scRNA-seq) and intracellular flow cytometry identified that HTLV-1c infection leads to dysregulated intrinsic apoptosis in infected cells in vivo. Pharmacological inhibition using BH3 mimetic compounds against MCL-1, but not BCL-2, BCL-XL, or BCL-w, killed HTLV-1c-infected cells in vitro and in vivo and significantly delayed disease progression when combined with tenofovir and dolutegravir in mice. Our data suggest that combination antiretroviral therapy with MCL-1 antagonism may represent an effective, clinically relevant, and potentially curative strategy against HTLV-1c
Gender differences in the prevalence and correlates of COVID-19 fear among mental health professionals: a network perspective based on a national survey in China
No full textBackground: Gender differences in COVID-19-related fear among mental health professionals (MHPs) have been inadequately studied. This study compared the gender differences in prevalence, correlates and network structure of COVID-19 fear among MHPs in China in the post-pandemic era. Methods: A nationwide cross-sectional study was conducted between January 22 and February 10, 2023. Binary logistic regression was used to identify factors associated with COVID-19 fear. Expected Influence was used to identify the most central (influential) symptoms in gender-specific networks, while network comparison tests were conducted to assess the differences between male and female models. Results: Among 7,199 MHPs, the overall prevalence of COVID-19 fear was 63.5% (95% CI: 62.3%-64.6%), with 61.7% (95% CI: 58.9%-64.4%) in males and 65.0% (95% CI: 63.7%-66.2%) in females. For male MHPs, factors associated with COVID-19 fear included having married status (OR: 1.39; 95% CI: 1.02–1.90; P = 0.037), poorer economic status (poor vs. good: OR: 1.91; 95% CI: 1.23–2.98; P = 0.004), more severe insomnia (OR: 1.04; 95% CI: 1.01–1.07; P = 0.018), and depression (OR: 1.09; 95% CI: 1.05–1.12; P < 0.001). For female MHPs, the significant factors included having married status (OR: 1.21; 95% CI: 1.06–1.37; P = 0.004), poorer economic status (poor vs. good: OR: 1.39; 95% CI: 1.11–1.73; P = 0.004), more severe insomnia (OR: 1.05; 95% CI: 1.03–1.06; P < 0.001), depression (OR: 1.09; 95% CI: 1.08–1.11; P < 0.001), and quarantine experience (OR: 1.17; 95% CI: 1.04–1.30; P = 0.006). Network analysis revealed that the most central symptom in the male network was FOC6 (sleep difficulties due to COVID-19 concerns), while the corresponding node in the female network model was FOC7 (palpitations when thinking about COVID-19). Conclusion: COVID-19-related fear was more prevalent among female MHPs than males. Specific interventions targeting the central symptoms in each network should be implemented to alleviate COVID-19 fear effectively and improve the mental health of MHPs in the post-pandemic era
"No doctor ever asked me...so I thought it wasn't a valid concern": Endometriosis patients' perspectives of barriers and facilitators to sexual health communication in general practice
No full textBACKGROUND: Sexual health communication between general practitioners (GPs) and individuals with chronic diseases is well documented as an important component of sexual well-being. However, a notable gap exists in understanding factors that contribute to sexual health communication in the endometriosis context. Endometriosis-related research has focused on the assessment of sexual functioning and its role in influencing health-related quality of life, with a limited understanding of the management of sexual well-being in primary healthcare settings. AIM: To explore how individuals with endometriosis perceive their experiences of sexual health communication with GPs to understand the barriers and facilitators of this communication in general practice. METHODS: This study formed part of a larger online quantitative survey measuring psychological and sexual well-being in individuals with endometriosis. In total 141 participants provided responses via open-ended unlimited free-text questions focused on their experiences of sexual health communication with GPs, including their perspectives on barriers and facilitators. RESULTS: Four overarching themes regarding barriers to sexual health communication were identified through thematic template analysis: (1) systemic factors; (2) practitioner factors; (3) patient factors; and (4) interpersonal factors. Facilitators mirrored strategies to address these barriers. Additionally, participants offered recommendations for developing resources to improve sexual health communication. CLINICAL IMPLICATIONS: Despite patients' interest, sexual health concerns in endometriosis are commonly overlooked in general practice due to various barriers, which individuals suggest could be addressed through comprehensive GP education and practical aids including communication tools. STRENGTHS AND LIMITATIONS: Although the sample is large for a qualitative study, the potential selection bias-stemming from participants' high levels of sexual dysfunction and motivation to discuss sexual health with a GP-may limit the diversity of perspectives. GP perspectives were not evaluated, precluding any assessment of the accuracy of individuals' perceptions of practitioner factors. CONCLUSIONS: Individuals with endometriosis encounter various systematic, practitioner, personal, and interpersonal factors that hinder or facilitate sexual health communication in general practice. Future research should prioritize strategies to improve sexual health communication for both GPs and patients
Hostility is Associated with Interferon γ Inducible Protein 10 in Opioid Maintenance Treatment Patients with Chronic Hepatitis C
No full textOBJECTIVE: Levels of circulating cytokines has been shown to be related to psychological distress. We have earlier shown that the symptoms of hostility may be related to levels of interferon γ inducible protein 10 (IP-10) in a group of general psychiatric in-patients receiving psychotropic medication. Here we investigate this association in a group of patients with chronic hepatitis C virus (HCV) infection with or without opioid maintenance treatment (OMT). METHODS: In a cross-sectional study, out-patients were interviewed for psychological distress using the Symptoms Check-List-90-R (SCL-90-R) and blood samples were drawn to measure serum levels of IP-10. Hierarchical linear regression analysis was used to investigate the association between hostility and IP-10 hostility in the whole group, and in the non-OMT and the OMT-patients, respectively. RESULTS: One hundred and twenty patients with chronic HCV infection were included, of whom 53 received OMT. There was no association between hostility and IP-10 in the patient group as a whole. In the OMT group we observed a negative association throughout the steps including adjusting for age, gender and BMI (β = -0.48, p = 0.011). CONCLUSION: We observed that only in OMT patients was there a negative association between hostility and IP-10. This might support previous findings that drugs, self-reported mental health symptoms and cytokines interact
Transforming Community-Based Rehabilitation Services: A National Redesign Using Experience-Based Co-Design
No full textBACKGROUND: To understand the experiences of clients, caregivers and staff in community day rehabilitation centres (DRCs) and identify areas for improvement in service processes and the clinical care of stroke, frailty and hip fracture, a national quality improvement project was undertaken using experience-based co-design (EBCD). The goal was to prioritise and co-design system-level changes for community-based rehabilitation care in Singapore. METHODS: The EBCD methodology comprised of eight stages: (1) site observations/time-motion studies, (2) interviews, (3) development of trigger film, (4) staff feedback events, (5) client/caregiver feedback events, (6) joint workshop, (7) small co-design groups and (8) celebration event. In addition, we collected surveys and case note reviews to capture the perceived and actual delivery of guideline-based care for stroke, frailty and hip fracture. RESULTS: Over a period of 2.6 years, we engaged over 80 clients and caregivers and 250 staff from 20 DRCs in the EBCD process. Triangulation of data from the site observations, interviews, surveys and case note reviews identified four themes: (1) Best practice care, (2) Person-centred care, (3) Allied health professional needs and (4) Service design. Person-centred care was desired by clients, caregivers and staff but was sometimes hindered by factors like tight scheduling and high turnover. Care was partially aligned with international guidelines, though some strongly recommended interventions were inconsistently delivered. Staff interviews and site observations revealed potential for more direct client care, teaching, research and quality improvement, with fewer administrative duties. New care models were sought, including social connections beyond DRCs, clearer maintenance rehabilitation criteria and financial incentives for transitioning to maintenance rehabilitation. A 12-min trigger film based on client/caregiver interviews was used during the feedback events and workshops. Three co-design workgroups were formed to develop clinical practice guidelines for stroke rehabilitation, a workplace learning framework for allied health, and community rehabilitation recommendations. CONCLUSION: EBCD was successfully used to identify gaps and co-design system-level solutions to improve community-based rehabilitation care in Singapore. Further solutions at the organisational and individual levels are needed. PATIENT OR PUBLIC CONTRIBUTION: Our study used EBCD to actively involve clients, caregivers and healthcare staff. Clients with lived experience of stroke, frailty and hip fracture identified key priorities and contributed to qualitative data interpretation during the feedback event. Notably, a trigger film incorporating clients' and caregivers' experiences of community rehabilitation services was developed and verified for accuracy during the feedback event, before being played at the joint workshop for all. During the joint workshop, priority statements for discussion were collaboratively identified, and solutions were co-developed. Clients and caregivers subsequently contributed to the development of the clinical practice guidelines for stroke rehabilitation. Throughout the project, the insights from clients and caregivers helped to ensure that our study's findings were relevant and actionable. We acknowledge the invaluable role of our patient and public partners in shaping this study and driving meaningful healthcare improvements
Impact of human lifestyle on the pathogenic potential of urban wastewater
No full textDomestic wastewater has been known for its pathogenic potential including the presence of pathogenic bacteria, virulence factor genes (VFGs) and antibiotic resistance genes (ARGs). While previous studies have investigated regional differences in microbial communities, the influence of population lifestyle factors on the pathogenic potential of wastewater microbiomes remains poorly understood. In this study, we analyzed ten Australian wastewater treatment plants (WWTPs) using Nanopore metagenomic sequencing to profile pathogens, ARGs, and VFGs, and examined their associations with health-related behaviors such as smoking, alcohol consumption, and obesity. A total of 196 pathogenic species, 951 ARG subtypes, and 380 VFGs were detected. Staphylococcus aureus was the most abundant pathogen, macB the dominant ARG, and lipooligosaccharides (LOS) the most prevalent VFG. While pathogen and ARG profiles were relatively stable across sites and showed limited association with lifestyle variables, VFG profiles demonstrated significant correlations with smoking rates, alcohol consumption, and nicotine levels in wastewater. Co-occurrence network analysis revealed strong interconnectivity among VFGs and between VFGs and ARGs, suggesting potential co-selection. Principal component analysis and diversity metrics further confirmed distinct patterns in VFG distribution across sites. These findings suggest VFGs as potentially sensitive indicators of behavioral health risks in wastewater-based epidemiology
Tin isotope systematics in subduction zones
No full textThe origin of slab components in arc lavas remains controversial with proposed sources including direct sediment melts, sediment-mantle mélanges, or crustal fluids. Stable isotope distributions of fluid-borne metals and those immobile in subduction components have the potential to trace the respective contribution of these components if placed into the context of additional magmatic differentiation and in conjunction with radiogenic isotopes. Here, we present the first high-precision double-spike tin abundances and isotope compositions in twenty-six arc rocks sampled along the Indonesian Sunda arc, a subduction zone with the highest subducted sediment volume globally. δ 122/118Sn3161a in these samples ranges from 0.13‰ to 0.46‰ and we find that Sn isotope compositions in Sunda arc rocks were affected by magmatic differentiation, superimposed on additional influences from components derived from the subducting slab. A step change in δ 122/118Sn3161a at 4–5wt.% MgO suggests the removal of heavier Sn isotopes, likely due to higher compatibility of isotopically heavier Sn4+ in Fe-Ti oxides along the liquid line of descent. This change of ∼0.1‰, however, is dwarfed by Sn isotope variations consistent with sediment melt contribution coupled with fluid addition from altered oceanic crust, both of which introduce lighter Sn isotopes. Sediment melt contamination increases with depth (temperature), but some exceptions at shallow sub-arc sources (depth ≤ 130 km) indicate additional melting of a mélange-style source. Our findings suggest the coexistence of mélange contributions, and deep fluid-induced melting plus partial sediment melts in the Sunda arc. Mélanges contribute only at shallow depths (≤130 km), consistent with their diapiric nature, whereas deeper levels favor fluid-fluxed melting and, at higher temperatures and pressures, partial sediment melting. This study provides insights into the complex interactions between fluids, sediments, and mantle wedge in subduction zones, highlighting the depth-dependent nature of slab contributions to arc magmatism. It also demonstrates the utility of Sn isotopes for tracing these processes and advancing our understanding of subduction zone geochemistry
Statactivism Up and Down the Stack: Dilemmas in the Estimation of AI’s Environmental Footprint
No full textAbstract
With mounting concerns regarding the environmental footprint of AI systems, the number and diversity of actors engaged in evaluating the sustainability of machine learning (ML) and artificial intelligence (AI) more broadly is growing. Based on nine semi-structured interviews with key experts, this paper investigates the dilemmas active participants in this global project face and the strategies they employ to overcome them. Our analysis shows that experts question the extent to which quantification fosters a radical enough version of change. Some evaluators want to make AI systems more “efficient” by reducing the amount of resources needed to develop AI models and infrastructures. Others critique this approach for failing to limit overall carbon emissions. Instead they insist on making AI “frugal”, an approach which expands the range of actions to mitigate AI’s indirect environmental impacts and includes consideration of whether AI is needed at all in each specific context. This tension creates situations of emotional discomfort and divided loyalties at two key moments: access to funding and expertise. In some cases, it leads some contributors to build coalitions of workers inside and across companies in order to challenge management, or to leave their organizations altogether
The Australian federal election of 3 May 2025: domestic issues amidst international turmoil
No full textThe 2025 Australian election resulted in a major win for the Labor Party. While the focus was on domestic issues, there was a backdrop of international turmoil resulting from the impact of President Donald Trump. Labor campaigned more effectively, winning strongly in two party preferred terms under the preferential voting system, although the primary vote for the major parties was weak. The domestic policies of the second Albanese government will be largely a continuation of the cautious approach adopted during the first term. Internationally the focus will be on protecting Australia’s economy and security, most clearly in reference to China and the US, but extending also to the various Commonwealth countries, especially the United Kingdom and those in the Indo-Pacific region
Keeping Safe Together: Exploring Men and Women's Experiences of a Pilot “All of Family” Domestic Violence Intervention Program in Melbourne, Australia
No full textThere are few interventions available to cater to domestic violence (DV) victim-survivors who are unwilling or unable to leave a violent situation. In recognition of this service gap, the Keeping Safe Together (KST) program piloted a support service to all family members in Victoria, Australia. This paper presents qualitative evaluation results for adult clients. Thirteen interviews were conducted with women victim-survivors (n = 8) and male perpetrators (n = 5). Findings revealed that women in the program experienced increased safety and supports while accountability processes were undertaken with men. Elements that required improvement included strengthening parents' understanding of how DV impacts children, and an appropriate and safe family therapy approach to DV