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Social isolation (SI) is associated with a higher risk of cardiovascular disease (CVD). One mechanism linking SI and CVD is accelerated biological ageing, which can be assessed using artificial intelligence-enabled electrocardiography (AI-ECG). We investigated whether longitudinal changes in SI status are associated with changes in biological ageing patterns. A retrospective longitudinal cohort study including 17 663 individuals without significant CVD who completed ≥2 Berkman and Syme Social Network Index and had paired ECGs within 1 year of each questionnaire. Longitudinal SI status was defined by comparing baseline and follow-up SI status. Ageing trends were assessed using Δage-gap, defined as the change in the gap between AI-ECG-predicted age and chronological age from baseline to follow-up. Linear regression models predicting Δage-gap and survival analyses with Kaplan-Meier and multivariable Cox regression for all-cause mortality were performed. Persistently connected individuals were older [63.1 (52.1, 70.6) years] and had a higher prevalence of hyperlipidaemia and hypertension, yet demonstrated more favourable ageing trajectories. Similarly, those who became connected showed a non-significant attenuation of accelerated ageing. In multivariable linear regression, being persistently isolated [β = +0.412 years, P < 0.001] or becoming isolated [β = +0.438 years, P = 0.012] was associated with accelerated ageing compared to being persistently connected. In survival analyses, becoming isolated (aHR = 1.94, 95% CI = 1.53-2.46, P < 0.001) and being persistently isolated (aHR = 1.66, 95% CI = 1.40-1.96, P < 0.001) were associated with significantly higher all-cause mortality, independent of chronological age and comorbidities. Persistent social connection is associated with slower biological ageing and lower mortality. The effects of SI on ageing and survival appear to be potentially reversible, calling for a prospective study to evaluate interventions aimed at improving both the social and biological burden of SI. Social isolation (SI) is a well-recognized yet underestimated risk factor for cardiovascular morbidity and mortality, and accelerated biological ageing is a key mechanism linking SI to cardiovascular disease. However, most studies rely on a single assessment of SI and of ageing, which fails to capture the dynamic nature of both entities. Our study showed that:Repeated measurements of SI provide greater insight into individual ageing trajectories than a one-time assessment.Persistent social connections over time are associated with slower ageing, whereas becoming isolated or being persistently isolated is linked to accelerated biological ageing.
Despite legal and ethical commitments to dignified end-of-life care, open communication with seriously ill patients remains inconsistent across the National Health Service (NHS). The Serious Illness Care Programme was implemented in two NHS hospital sites to improve communication and care planning for patients with serious illness. Explore the lived experiences of seriously ill patients and their clinicians participating in Serious Illness Conversations. Qualitative study using a phenomenological approach within an interpretive paradigm. Narrative interviews were undertaken, and Reflexive Thematic Analysis was used to identify patterns of meaning. Outpatient clinics in two NHS hospital sites: a tertiary cancer centre and a renal unit within a city teaching hospital. Fourteen patients (seven cancer, seven renal failure) and nine clinicians (six oncologists, three nephrologists) were interviewed. The following three interrelated themes were generated from the analysis: (1) Patients described the conversations as 'a transformative experience', fostering reflection, practical planning, and reframed hope despite a limited prognosis; (2) Serious Illness Conversations were 'different conversations' from routine consultations, with use of the Serious Illness Conversation Guide enabling deeper, more holistic dialogue; however, they were segregated from routine practice; (3) Systemic and cultural barriers hindered these conversations from becoming embedded, perpetuating inequity of access to these conversations: 'Systems, Structure, Process: Serious Illness Conversations, epistemic injustice and cultural violence'. Findings from this study directly challenge the commonly held belief that these conversations are inherently negative to reveal the transformative power of these important and necessary conversations. They opened up different types of conversations, giving patients agency to direct certain aspects of their life. However, their integration into routine practice is hindered by structural and cultural constraints. Addressing these barriers is essential to ensure all patients have equitable access to these conversations. Patient and clinician experiences of serious illness conversations in NHS Hospitals in the UK This study explored how seriously ill patients, and the clinicians who care for them, experienced Serious Illness Conversations in two NHS acute hospitals. Serious Illness Conversations are structured conversations designed to help patients talk about their future, their values, and what matters most to them, to align their care with their wishes. Interviews were undertaken with 14 patients (7 with cancer and 7 with kidney failure) and 9 clinicians (6 oncologists and 3 nephrologists). Patients described the Serious Illness Conversations as transformative. They gave patients space to reflect, plan practically, and reframe hope even when facing a limited prognosis. Patients appreciated clinicians’ willingness to talk openly and honestly about dying and the future. The conversation enhanced their understanding about their illness and enabled them to make decisions about their care and prepare for the future. Clinicians recognised the value of these conversations, which promoted more holistic conversations that went beyond diagnosis and treatment. The Serious Illness Conversation Guide provided a framework for clinicians to structure these conversations with their patients. However, they were seen as different conversations that were organised in addition to routine clinic appointments, making them difficult to integrate into their already busy schedules. Access to Serious Illness Conversations was also unequal. Decisions about which patients were invited were made by clinicians, not patients. Clinicians often faced organisational barriers preventing them from scheduling these conversations such as a lack of available time and space within the hospital setting. This study concluded that Serious Illness Conversations can be powerful and positive for patients and clinicians, but structural and cultural barriers prevent them from becoming routine. Addressing these barriers is essential to ensure all patients have equal access to these conversations.
Recurrent drought events are becoming increasingly frequent under climate change, yet how perennial clonal grasses adjust their functional traits and recovery trajectories across repeated drought-recovery cycles remain poorly understood. Here, we examined whether exogenous application of methyl jasmonate (MeJA) modifies physiological performance, biomass allocation, and recovery dynamics of the clonal grass Festuca rubra under recurrent drought. Plants were exposed to three consecutive drought-recovery cycles in a controlled growth-chamber experiment with factorial drought and MeJA treatments. We quantified physiological traits (chlorophyll concentration, maximum quantum efficiency of PSII), structural traits (specific leaf area, leaf dry matter content), and performance-related traits (ramet number and biomass allocation). Recurrent drought progressively reduced photosynthetic performance and ramet production, with recovery becoming increasingly incomplete across cycles. In contrast, MeJA treatment mitigated drought-induced declines in chlorophyll concentration and PSII efficiency and stabilized recovery responses. MeJA also altered biomass allocation patterns, increasing aboveground biomass and reducing root-to-shoot ratios under drought, in contrast to drought-only plants, which showed enhanced belowground investment. Post-hoc analyses revealed that MeJA + drought plants differed significantly from drought-only plants for aboveground biomass and several functional traits. Overall, our results demonstrate that MeJA modulates drought responses and recovery trajectories in F. rubra, promoting conservative trait expression and improved performance under recurrent drought. These findings highlight the potential role.
Although space travel is becoming more accessible, our understanding of how the space environment and microgravity (μG) affect biology, physiology, and human health remains incomplete. This study examined the effects of μG on synaptic signaling and neuromuscular aging in Caenorhabditis elegans. The D01 cohort, consisting of L4 larvae to young adults raised in μG, exhibited a downregulation of genes linked to synaptic signaling, dopamine response, locomotion, cuticle development, and mitochondrial metabolism. This was accompanied by altered synapse dynamics, reduced motility, and shorter body length. In μG, aged worms showed a reduction in collagen gene expression, increased abnormalities in motor neuron morphology, changes in synaptic vesicle dynamics, and a collapse of mitochondrial morphology in body wall muscles, highlighting exacerbated aging-like phenotypes. The gentle-touch mechanoreceptor MEC-4 was identified as a key mediator of μG-induced body length reduction and changes in extracellular matrix gene expression. mec-4 mutants did not show μG-associated body shortening. The expression of most mechanoreceptor genes, including stretch-activated channels unc-105 and del-1, was downregulated under μG conditions. Notably, the expression of tmc-1 and degt-1 mechanoreceptor genes was downregulated independently of MEC-4. Restoration of physical stimulation using culture medium with small beads in space mitigated many μG-induced neuromuscular defects and expression alterations including those in mechanoreceptor genes. These results highlight the role of mechanical stimuli in maintaining neuromuscular integrity during spaceflight and suggest that restoring tactile input could counter health risks from reduced tactile stimulation during long-term space missions.
This study examines whether recreational marijuana (RM) legalization in neighboring states is associated with driving under the influence of marijuana in a non-legalizing state, as measured by motor-vehicle crashes involving a marijuana-positive driver (MP). Although Pennsylvania has not legalized RM, it borders five states that legalized RM at different time points in 2021 and 2023. This spatial and temporal variation enables a quasi-experimental stepped wedge design that assesses whether Pennsylvania counties that border a state with RM legalization experienced changes in MP motor-vehicle crash counts. Pennsylvania Department of Transportation data provide crash counts at the county-month level (January 2019-December 2024). Of primary interest are MP crashes where the Pennsylvania State Police (PSP) was the reporting law enforcement agency (MP-PSP). Once RM legalization occurs in a contiguous state, a Pennsylvania county (N=27) bordering that state becomes Post-Exposure. Four Pennsylvania counties eventually bordered two states with RM legalization, becoming Post-Second-Exposure. Poisson regression was used to estimate changes in crashes in the Post-Exposure and Post-Second-Exposure periods relative to the Pre-Exposure period. On average, a Pennsylvania county experienced a significant 58.41% increase in MP-PSP crashes Post-Exposure and a nonsignificant 55.48% increase Post-Second-Exposure. Where a border county has an interstate highway (N=20), on average, there was a significant 68.95% increase Post-Exposure and a nonsignificant 56.80% increase Post-Second-Exposure. RM legalization in bordering states may impact traffic safety in a state that has not yet legalized RM. Future research should identify mechanisms for this association as well as actionable strategies to prevent marijuana-impaired driving.
Providing care for older family members (e.g., parents or relatives) and fulfilling one's work responsibilities, known as family eldercare, is becoming increasingly common due to the growing population of older adults in many societies. A burgeoning literature has begun investigating the negative spillover effects of eldercare burden on employees' experiences and performance at work. In particular, scholars have called for more attention to identifying effective strategies for coping with eldercare burden and mitigating its negative impact. The present research examined whether challenge appraisals of eldercare could mitigate the effect of eldercare burden on employees' positive affect, which, in turn, was related to their sense of thriving at work. In two studies-an experiment and a 2-week experience sampling study-we found that challenge appraisals weakened the relationship between eldercare burden and employees' positive affect. Employees' challenge appraisals also weakened the indirect relationship between eldercare burden and thriving at work through positive affect. This research demonstrates that employees' eldercare burden negatively spills over into the work domain. However, challenge appraisals of eldercare can buffer this spillover process. Theoretical and practical implications are discussed. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Due to climate change, extreme weather events are becoming more frequent, which include days with higher temperatures, especially in the summer period. These more frequent heat events can have physiological consequences on dairy cattle when the ambient temperature exceeds their thermoneutral zone. The present study analysed heat stress effects on milk yield in three German dairy cattle breeds with data from southwest Germany. Daily milking and climate data (temperature and humidity) were collected between June 2022 and December 2024 from 5 182 dairy cattle from German Holstein Friesian, German Fleckvieh, and German Brown Swiss, on 46 farms in the state Baden-Württemberg, Germany. The milk yield was modelled as a function of the temperature-humidity index (THI). The average daily THI was determined and transformed by a double hinge function. Random regression reaction norm models with higher order Legendre polynomials were used to describe the genetic variation in milk yield across different THIs. The estimated variances of the animal effect in relation to the environmental variances were comparable across the breeds. The pattern of additive genetic variance was nearly linear, while the permanent environmental variance followed a u-shaped curve along the THI trajectory for all three breeds. Genetic correlations of milk yields at different THIs were small and, in a few cases, also negative for larger differences between THI, which implies that animals vary genetically in their response to thermal conditions. These correlations must be validated using large data sets. Breeding for improved heat tolerance and overall resilience towards thermal stress is expected to become an important objective, particularly considering the rising frequency of heat extremes.
Volar locking plates become the standard treatment for distal radius fractures and are mostly applied through volar approaches that rely on the flexor carpi radialis (FCR) as a superficial landmark. Although usually straightforward, anomalous flexor musculature may complicate exposure, misdirect dissection and increase the risk of iatrogenic neurovascular injury. We report two rare anatomical variants encountered during open reduction and internal fixation: FCR brevis (FCRB) associated with anomalous insertion of the pronator quadratus, and complete agenesis of the FCR. Both substantially altered the expected surgical anatomy. The FCRB obscured the typical superficial interval and was associated with ulnar displacement of the pronator quadratus on deeper dissection. In the second case, the absence of the FCR eliminated a key landmark, with the palmaris longus becoming the most radial tendon, increasing the risk of inadvertent ulnar dissection towards the median nerve and its palmar cutaneous branch. Recognition of these variants is essential to ensure safe volar exposure and avoid neurovascular injury. Level of Evidence: Level V (Therapeutic).
Obesity is a multi-faceted health problem impacting many aspects of health-related quality of life (HRQoL). Although the clinical effectiveness of metabolic bariatric surgery (MBS) is well-documented across different settings, qualitative studies on post-MBS HRQoL involving Asian patients remain scarce. This study aimed to qualitatively explore the HRQoL of people with obesity and post-MBS individuals within a Southeast Asian context. In-depth interviews were conducted with people with lived experience with obesity who were visiting a hospital weight management clinic in Singapore, using a semi-structured interview guide. A total of 25 study participants were recruited, including those who had and had not received MBS. Data was analysed using an inductive thematic approach. People with obesity reported substantial symptom burden and impaired physical functioning, issues with appearance and clothing, challenges with romantic relationship or physical intimacy, poor social well-being, and poor psychological and emotional well-being. Post-MBS patients also reported challenges, including loose skin and hair loss affecting appearance, as well as changes in eating habits and reduced food enjoyment. While Southeast Asians with obesity experience HRQoL deficits in similar domains as their counterparts in Western populations, their social well-being, particularly fear of becoming a burden to others, might be more affected. This study highlights the need for culturally sensitive HRQoL measures when assessing the pre- and post-operative outcomes of MBS in Singapore. Qualitative studies concerning the health-related quality of life of people with obesity who have and have not received metabolic bariatric surgery remain scarce in Asia. This study aimed to qualitatively explore the health-related quality of life of people with obesity and post-MBS individuals within a Southeast Asian context. We interviewed a total of 15 people with obesity who have not received MBS and 10 post-MBS persons. All participants shared how obesity affected their health-related quality of life. In addition, post-MBS persons were also asked about their post-MBS health-related quality of life. People with obesity reported a wide range of symptoms (e.g. breathlessness, pain and discomfort) and impaired physical functioning (mobility and abilities to perform usual activities), issues with appearance and clothing, challenges with romantic relationships or physical intimacy, poor social well-being, and poor psychological and emotional well-being. Post-MBS individuals also reported challenges including loose skin and hair loss affecting appearance, as well as changes in eating habits and reduced food enjoyment.
Pseudomonas is one of the largest genera among Gram-negative bacteria, currently comprising nearly 400 valid species. Among them, non-aeruginosa Pseudomonas species, together with Stutzerimonas-a genus recently separated from Pseudomonas-are becoming important reservoirs of antimicrobial resistance genes. However, accurate species-level identification of these organisms remains challenging when relying on the methods routinely implemented in most clinical microbiology laboratories, such as MALDI-TOF mass spectrometry. Therefore, this study aimed to identify and characterize metallo-β-lactamase-producing non-aeruginosa Pseudomonas spp. and Stutzerimonas spp. isolates obtained in a Spanish tertiary hospital, focusing on their species-level identification, dissemination and role as reservoirs of carbapenemase-encoding genes. Whole-genome sequencing (WGS) and antimicrobial susceptibility testing (AST) were used to identify and characterize a total of 22 carbapenemase-producing non-aeruginosa Pseudomonas and Stutzerimonas isolates collected from patient and environmental samples from March 2022 to July 2024 in a Spanish tertiary hospital. WGS analysis identified eight species: Pseudomonas alloputida (n = 7), Pseudomonas mosselii (n = 5), Pseudomonas kurunegalensis (n = 4), Pseudomonas asiatica (n = 2), Pseudomonas oleovorans (n = 1), Pseudomonas soli (n = 1), Stutzerimonas chloritidismutans (n = 1) and Stutzerimonas stutzeri (n = 1). Multilocus sequence typing (MLST) classified isolates of the P. putida group into nine STs, revealing three predominant clones: P. alloputida ST69, P. mosselii ST115 and P. kurunegalensis ST114. AST results showed resistance rates >55% to all tested β-lactams, aminoglycosides and fluoroquinolones, except for cefiderocol, amikacin and colistin (0-5%). The following carbapenemase combinations were detected: bla VIM-1 (n = 16), bla VIM-1+bla VIM-2 (n = 4), bla VIM-1+bla NDM-1 (n = 1) and bla VIM-11 (n = 1). Seven distinct bla VIM-harboring plasmids were detected in 16 isolates, whereas the remaining six carried chromosomally-integrated bla VIM. Eight different bla VIM-harboring class I integrons were detected, two of which also occurred in P. aeruginosa clinical isolates obtained in the same hospital. This study highlights the epidemiological relevance of non-aeruginosa Pseudomonas and Stutzerimonas species as reservoirs of metallo-β-lactamase genes encoded in mobile genetic elements. These findings reinforce the need for systematic WGS-based surveillance of both clinical and environmental isolates, enabling the detection of hidden transmission networks and interspecies dissemination of antimicrobial resistance determinants.
Antimicrobial resistance (AMR) is a major threat in oncology, where immunosuppression and repeated healthcare exposure increase susceptibility to severe infections. Multicenter data on antibiotic resistance patterns among cancer patients in Iraq remain limited. A multicenter observational study was conducted across three oncology centers in Iraq between January 2024 and March 2025. A total of 125 non-duplicate blood culture isolates from patients with hematological and solid malignancies were analyzed, including 100 resistant and 25 susceptible isolates. Antibiotic susceptibility testing followed Clinical and Laboratory Standards Institute criteria, and categorical variables were analyzed using chi-square tests. Multidrug-resistant and carbapenem-resistant phenotypes were frequent among Klebsiella pneumoniae (35/100, 35%), Escherichia coli (36/100, 36%), and Pseudomonas aeruginosa (29/100, 29%). P. aeruginosa showed the highest burden of advanced resistance phenotypes, including difficult-to-treat resistance. Resistant isolates were more common in patients with hematological malignancies (77/100, 77%) than in those with solid tumors (23/100, 23%). Resistance was prominent for third-generation cephalosporins, fluoroquinolones, and β-lactam/β-lactamase inhibitor combinations, whereas tigecycline and colistin retained greater activity against several resistant isolates. This study identified substantial antibiotic resistance among bloodstream isolates from cancer patients in Iraq, supporting oncology-specific surveillance and antimicrobial stewardship. People with cancer are more likely to get serious infections because their immune system is weakened by the disease and its treatments. These infections are becoming harder to treat due to antibiotic resistance, where bacteria no longer respond well to commonly used medicines. In Iraq, there is limited information about how serious this problem is across different cancer centers. This study looked at blood infections in cancer patients from three hospitals in Iraq. It found that most infections (about 80%) were caused by bacteria that were resistant to antibiotics. These resistant infections were more common in patients with blood cancers than in those with solid tumors. The most common bacteria identified were Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa, many of which were resistant to several commonly used antibiotics. These findings show that antibiotic resistance is a major concern for cancer patients in Iraq. Regular monitoring of infection patterns and careful use of antibiotics are important steps to improve treatment outcomes and protect this vulnerable group of patients.
Occupational health and safety management system (OHSMS) programs are designed to create safer workplaces. However, research on their effectiveness is limited in terms of representation and rigor. This study evaluates whether firms that obtained an OHSMS certification via the Certificate of Recognition (COR) program experienced greater injury rate reductions than similar non-certified firms in Ontario, Canada. Using firm and claim-level data from the Workplace Safety and Insurance Board and COR registration data from the Infrastructure Health and Safety Association, the effect of becoming certified on firm-level injury rates was assessed using a matched difference-in-differences study design with population averaged negative binomial regression models. A total of 346 certified firms were matched with 310 non-certified firms during the years 2009 to 2020. Firms that became certified were associated with a greater reduction in the lost time injury rate (incidence rate ratio (IRR): 0.72; 95% confidence interval (CI): 0.63-0.84), high-impact injury rate (IRR: 0.80, 95% CI: 0.66-0.97) and no reduction in the no lost time injury rate (IRR: 1.00, 95% CI: 0.92-1.08) relative to the change in similar non-certified firms. The effectiveness of certification was strongest in firms that were recently certified, larger, and in the construction sector. The findings suggest that COR can be an effective program in reducing injury rates in construction firms, and among larger and more recently certified firms. It is less effective in smaller and earlier certified firms, and not effective in non-construction firms. Furthermore, the effectiveness in construction firms may be subject to unmeasured selection bias. OHSMS program evaluations can inform decision-makers on when, and under what circumstances programs work and where improvements can be made. In particular, the COR program appears most effective for large construction firms whereas small construction firms may benefit from other tools.
Physical inactivity remains a persistent global health challenge despite long-standing evidence that regular physical activity (PA) reduces chronic disease risk, cognitive decline and premature mortality. In parallel, digital health technologies have expanded rapidly, yet it remains unclear how distinct platform types have emerged, diffused and been differentially adopted in clinical vs. non-clinical populations. We conducted a large-scale bibliometric trend analysis of technology-supported PA interventions indexed in Scopus and SportDiscus, covering records published from 1953 to 2025. Using an active-learning screening workflow with title/abstract screening, sensitivity checks and consensus adjudication, we identified 2,981 eligible studies published between 1988 and 2025 across 757 journals and 63 countries. Studies were coded by population (clinical vs. non-clinical), platform cluster, and author-reported PA outcome direction abstracted from the publication record. Publications increased markedly after 2008, with smartphone/mHealth and wearable sensors becoming the dominant platform clusters in the 2010s and early 2020s. In the smoothed overall trajectories, publication activity reached its highest level around 2022, followed by a contraction concentrated mainly in mature clinical platform clusters. Non-clinical studies generally adopted newer platforms earlier, whereas clinical studies showed a recurrent lag before converging for more established, accessible technologies. A distinct population-level reversal was visible in mature platforms: non-clinical studies led early smartphone, wearable and web-based uptake, clinical studies became more prominent around the COVID-19 period, and non-clinical studies again predominated by 2025 for smartphone/mHealth, wearable sensors and web applications. Multi-component designs were common, with the strongest network backbone centred on smartphone, wearable and web-based combinations. Reported PA improvement signals were common across both population strata, but these findings reflect patterns in published study reporting rather than comparative effectiveness. By providing a platform-centred, cross-population and temporally resolved map of technology-enabled PA interventions, this study identifies mature technology backbones, emerging areas of experimentation, and recurrent translational gaps between clinical and non-clinical contexts. The findings support more theory-informed and implementation-aware intervention design while underscoring that bibliometric prominence should not be equated with real-world efficacy.
In the new era characterized by the accelerated integration of science, technology, and industry, artificial intelligence (AI) is increasingly becoming a core force driving enterprise transformation. Innovation serves as the primary engine of rapid corporate development, with employee creativity being the key to such innovation. As an externally enabling technological tool, AI not only effectively extends the boundaries of employee creativity but also significantly unlocks employees' innovative potential. Therefore, enhancement of employee creativity is closely related to the effective utilization of AI technology. Based on conservation of resources theory and social exchange theory, this study develops a research model to investigate how AI usage affects employee creativity. Moreover, previous studies have predominantly focused on modeling mediating effects. To address this research gap, the present study broadens its scope by incorporating the moderating role of technology acceptance and examining its effects. Targeting Chinese SMEs, the study collected 316 samples and performed empirical analyses using SPSS and Amos. The findings reveal that AI usage influences employee creativity through work engagement. In addition, the interaction between technology acceptance and AI usage amplifies the effects on both work engagement and employee creativity. Theoretically, this study advances interdisciplinary research by integrating AI technology with organizational behavior, thus establishing a foundation for subsequent studies. Practically, it provides concrete guidance for Chinese SMEs in their digital transformation endeavors.
Helicobacter pylori colonizes the gastric mucosa of around half of the world's population and is a major cause of chronic gastritis, peptic ulcer disease, and gastric cancer. Current therapies are becoming increasingly ineffective due to the rapid spread of antibiotic resistance, creating an urgent need for new treatment options with distinct mechanisms of action. Drug repurposing offers a practical and cost-effective approach to address this gap. PBT2 is an 8-hydroxyquinoline derivative originally developed for the treatment of neurodegenerative diseases and has more recently been shown to possess antimicrobial activity. In this study, we demonstrate that PBT2 displays potent bactericidal activity against H. pylori, including multidrug-resistant clinical isolates. PBT2 rapidly killed H. pylori in vitro at low concentrations, with faster killing kinetics than commonly used antibiotics, and no resistance was detected after 30 days of continuous exposure. Importantly, PBT2 was effective in clearing an H. pylori infection in a murine model. Quantitative sequential window acquisition of all theoretical-mass spectrometry proteomic analysis revealed that PBT2 triggers broad disruption of essential bacterial processes, including global suppression of translation, impairment of iron-sulfur cluster assembly and respiration, dysregulation of metal homeostasis, and reduced abundance of virulence- and motility-associated proteins. We reported that PBT2 can act as a nickel ionophore, with Ni2+ being the highest-affinity ligand for PBT2 reported to date. Together, these findings suggest that PBT2 acts through a multifaceted, metal-dependent mode of action that limits the potential for emergence of resistance. Our work highlights PBT2 as a promising candidate for repurposing to treat multidrug-resistant H. pylori infections.IMPORTANCEAntibiotic resistance is steadily reducing our ability to treat common bacterial infections, while the development of new antibiotics has slowed. Helicobacter pylori is a clear example of this growing problem, with treatment failures becoming more common worldwide. This study highlights the value of taking a different approach by repurposing existing drugs for new antibacterial uses. Rather than acting on a single bacterial target, the compound examined here disrupts multiple essential processes at once, reducing the probability of resistance developing.
Opioid use disorder (OUD) among US adolescents represents a public health crisis, with overdose deaths becoming a leading cause of mortality. Despite their efficacy, naloxone and buprenorphine remain underutilized. The pediatric emergency department (PED) presents an intervention opportunity, as many adolescents with OUD present there before fatal overdoses. This quality improvement initiative examined the use of education and hybrid screening to improve the provision of naloxone and buprenorphine in the PED. A multifaceted OUD screening and treatment protocol was implemented in a PED using Best Practice Alerts (BPA) triggered by specific chief complaints (CC), alerting providers to the need for additional screening. Components included provider education, formulary changes, and clinical pathways. Data from adolescent encounters over 45 months were analyzed, comparing naloxone and buprenorphine prescribing rates before and after implementation. Secondary analyses examined demographics, insurance, and psychiatric comorbidities. During the study, 63 adolescents initiated buprenorphine, and 246 received naloxone. Among patients with BPA-qualifying CCs, naloxone dispensing increased from 3.89% to 11.39% and buprenorphine prescribing increased from 1.04% to 2.46%. Postimplementation, Black/African American adolescents and those with government insurance received more medications than peers, and overall naloxone prescribing increased from 0.4% to 0.79% of all visits. Patients triggering the BPA experienced longer ED stays regardless of medication receipt, with no increase in return visits. Electronic screening alerts coupled with provider education increased the provision of medications for adolescents at risk for opioid-related harm. The intervention is achievable in a PED without increasing return visits.
Recovery in eating disorders (EDs) is often defined in terms of symptom remission, potentially overlooking the broader meanings individuals attribute to illness and recovery. Qualitative research has highlighted the multidimensional nature of recovery, yet less is known about how therapeutic contexts may shape how individuals make sense of illness, change, and recovery. This study aimed to explore how individuals with EDs conceptualize illness and recovery, and how these meanings may be shaped through participation in group psychotherapy. A qualitative study was conducted within an interpretivist framework using reflexive thematic analysis. Ten adult outpatients with EDs participated in semi-structured interviews at the end of a group psychotherapy program integrated within a multidisciplinary treatment setting. Participants described a shift from understanding the ED mainly through food, weight, body image, and symptom control toward a more emotionally and relationally informed understanding of distress. Recovery was increasingly constructed as a multidimensional and non-linear process involving emotional awareness, self-acceptance, agency, identity renegotiation, and connection with others. The group was experienced as a space that fostered recognition, belonging, and reflection, while also exposing participants to shame, fear of judgment, and emotional vulnerability. Findings suggest that group psychotherapy may support a reconfiguration of how individuals with EDs understand illness and recovery, moving from a primarily symptom-centred perspective toward a more holistic, relational, and personally meaningful framework. Rather than operating mainly through direct behavioural change, the group appeared to function as a space for meaning-making, emotional reflection, and relational experimentation. This study highlights emotional awareness, identity renegotiation, self-acceptance, and interpersonal connection as potential targets for fostering recovery in EDs. Trial registration The study protocol (n. 0034565/i) was approved by the local Institutional Review Board. Eating disorders are often understood mainly in terms of eating behaviours, weight, and body image. However, people with eating disorders may experience illness and recovery in broader and more personal ways, involving emotions, relationships, identity, shame, and self-acceptance. This study explored how adults with eating disorders understood their illness and recovery after taking part in group therapy within a multidisciplinary treatment setting. Ten adults were interviewed after completing a group therapy program. Before the group experience, participants often described their eating disorder mainly through symptoms such as food restriction, bingeing, purging, body dissatisfaction, and weight control. After the group, many described their difficulties in a broader way, linking the eating disorder to emotions, relationships, and personal experiences. Recovery was seen not only as reducing symptoms, but also as becoming more aware of emotions, accepting oneself, developing personal agency, and connecting with others. The group helped some participants feel understood and less alone, but it could also involve shame, fear of judgment, and emotional vulnerability. Overall, group therapy appeared to support broader and more personally meaningful understandings of recovery.
Chronic kidney disease (CKD) significantly affects kidney function, often leading to end-stage kidney disease (ESKD). Due to its high rates of morbidity, mortality, and economic effects, CKD is becoming the ninth most important risk factor for mortality worldwide, presenting serious healthcare issues. Regulatory T lymphocytes (Tregs) play a role in regulation, particularly in transplant tolerance and autoimmune conditions. Recent research has highlighted the potential of Tregderived vehicles (EVs) to modulate responses and promote graft tolerance during kidney transplantation. These EVs can suppress effector T lymphocytes (T effect), trigger apoptosis, and modify cytokine production to maintain balance and prevent graft rejection. Moreover, Treg-EVs have emerged as potential biomarkers for diagnosing CKD, paving the way for new diagnostic and therapeutic strategies. This study explores how Treg-derived EVs influence processes underlying CKD and kidney transplantation, highlighting their significance as useful tools.