Language is thought to have multiple sensitive periods in early childhood, but the neural basis of these sensitive periods is less understood. We leverage advances in in-vivo neuroimaging of plasticity, measuring the neural inhibition across the brain via Hurst exponent. Using two large datasets with children ages 10 months to 18 years (Baby Connectome Project: 10m-3y6m, 458 observations across n = 222 children; Human Connectome Project-Development: 5-18y, n = 437), we characterize the development of the Hurst exponent in language-related brain regions. In early childhood, Hurst increases in temporal and frontal language areas, and posterior regions develop earlier than anterior regions. In contrast, thalamic Hurst plateaus earlier, perhaps underlying the earliest language-related sensitive periods. Children with higher language-related skills show slower increases in cortical Hurst in early childhood, suggesting protracted plasticity. Later in childhood, cortical Hurst plateaus around age 9, suggesting a potential neural mechanism for age-related declines syntax learning. These results highlight a potential neural basis for cascading language-related sensitive periods.
IntroductionInformal caregivers provide essential assistance to older adults living at home, but can experience burden and unmet needs. While caregiver burden is well studied, its conceptual boundaries and relationship to unmet needs remain unclear. This cross-sectional study examined the associations of caregiver-reported unmet needs and burden-related indicators with excellent well-being among informal caregivers.MethodsA cross-sectional survey was conducted among 352 informal caregivers of older adults receiving home nursing services in Iceland, using the interRAI Self-Reported Carer Needs (SCaN) assessment. Caregiver well-being was dichotomized into excellent and non-excellent. A hierarchical logistic regression model was used to examine associations of caregiver-reported unmet needs and burden-related indicators with excellent well-being.ResultsThe most frequently reported caregiver unmet needs concerned episodic relief (44.5%), psychological counseling (31.6%), and health education (30.5%). In the final hierarchical model, caregiver-reported care-recipient unmet need for housing adaptation (OR = 0.42, 95% CI [0.19-0.92]) and caregiver unmet need for psychological counseling (OR = 0.44, 95% CI [0.22-0.85]) were associated with lower odds of excellent well-being. Decreased social activities due to caregiving (OR = 0.47, 95% CI [0.24-0.95]), perceiving caregiving as a source of stress (OR = 0.37, 95% CI [0.19-0.72]), and higher multifaceted strain (OR = 0.87, 95% CI [0.81-0.94]) were also associated with lower odds of excellent well-being.ConclusionsCaregiver-reported unmet needs and burden-related indicators were associated with excellent caregiver well-being. Systematic caregiver assessments may help identify both support gaps and subjective strain, informing targeted support for informal caregivers.
To evaluate magnetic resonance imaging features and the natural course of granulomatous prostatitis after intravesical Bacillus Calmette-Guérin therapy in patients with bladder cancer. Using a radiologic report keyword search program, data were collected from magnetic resonance images between March 2018 and August 2023. A total of 241 baseline or follow-up magnetic resonance images of 64 patients with pathologically or clinically confirmed Bacillus Calmette-Guérin-related granulomatous prostatitis were retrospectively included. We investigated intravesical Bacillus Calmette-Guérin history, lesion size changes, and serum prostate-specific antigen changes through a chart review. Lesion imaging features were assessed on T1-. T2-, diffusion-, and contrast-enhanced T1-weighted images and classified based on enhancement degree and presence of diffusion restriction. The completely improved group (n = 12), incompletely improved group (n = 26), and recurrent inflammation group (n = 13) were identified according to temporal magnetic resonance imaging changes of granulomatous prostatitis. Patients who underwent radical cystectomy or were lost to follow-up were excluded due to unknown outcomes (n = 13). Among 64 patients, subtle increased T1 signal intensity with granulomatous inflammation was observed in 57 (89.1%). The baseline prostate-specific antigen level in the recurrent inflammation group was 2.00 ± 1.26 ng/mL, which was higher than the 1.0-1.1 ng/mL levels in the other groups (P = 0.050). Even if the lesion completely improved on magnetic resonance imaging, the serum prostate-specific antigen level increased by approximately 2.0 times compared to the baseline level. Lesion peak size (26.0 ± 15.0 mm) in the incompletely improving group was significantly larger than that in the other groups (14.8 ± 5.8 and 17.0 ± 9.1 mm) (P = 0.006). Among the 77 initial magnetic resonance images, type A (n = 30, strong enhancement and diffusion restriction), type B (n = 25, rim enhancement with diffusion restriction), and mixed type (n = 19) were the most common. In the last 50 magnetic resonance images, type C (n = 34; no enhancement or diffusion restriction) was predominant. In patients who underwent intravesical Bacillus Calmette-Guérin therapy, bladder magnetic resonance imaging frequently revealed subtle T1-hyperintense lesion in the prostate with diffuse or rim-like enhancement accompanied by markedly restricted diffusion, which is highly suggestive of Bacillus Calmette-Guérin-related granulomatous prostatitis and tends to spontaneously regress on follow-up imaging. Even with radiological improvement, prostate-specific antigen levels may remain elevated and should not be mistaken for malignancy.
Accurate detection of acetylcholinesterase (AChE) activity and screening of its inhibitor drugs are crucial for detecting and intervening in neurodegenerative or aging-associated diseases. Herein, a sensitive and reliable ratiometric fluorescence platform is developed for sensing AChE activity and its inhibitor drugs. This strategy is based on an AZM hybrid, which is constructed by self-assembling a MOF@MOF architecture (ZIF8@MIL101(Al)) with AgAu nanoclusters (AgAuNCs) via electrostatic interactions. ZIF8 serves to enhance the fluorescence of AgAuNCs, while MIL101(Al) acts as a stable reference probe. Upon introduction of AChE and the substrate acetylthiocholine (ATCh), the generated thiocholine (TCh) quenches the AgAuNC fluorescence, whereas the MIL101(Al) signal stays constant, leading to a concentration-dependent change in the fluorescence intensity ratio. The ratiometric response enables sensitive detection of AChE activity with a limit of detection (LOD) of 0.032 U L-1. The platform is applied to AChE determination in human serum samples. The system demonstrates the feasibility of inhibitor screening with tacrine as a model inhibitor. This work provides a simple ratiometric platform that holds promise for AChE-related clinical diagnosis and drug discovery.
Those at risk of diabetes-related foot ulceration (DFU) must balance sufficient physical activity to maintain glycaemic control and cardiovascular health whilst avoiding excessive trauma to their feet. Our systematic review aimed to assess whether physical inactivity and/or sedentary behaviour affect DFU outcomes. Embase, Medline, and Scopus were searched for peer-reviewed studies using the criteria: ('diabetes' OR 'diabetic') AND ('physical*' OR 'activ*' OR 'inactiv*' OR 'sedentary') AND 'foot' AND 'ulcer', returning 4650 results excluding duplicates. 16 studies were included and assessed for risk of bias using the Newcastle-Ottawa Scale (NOS). Fifteen studies assessed physical inactivity and 1 assessed both inactivity and sedentary behaviour and DFU outcomes. Eleven of 16 (69%) studies reported significantly greater likelihood of DFU in inactive participants. Exploratory meta-analysis suggested physical inactivity to be associated with doubled DFU risk (OR 2.09, 95% CI 1.32-3.32, p = 0.002). Evidence that sedentary behaviour was associated with tripled DFU risk was based on a single prospective cohort and had a high risk of bias (OR 2.95, 95% CI: 1.5-6.4, p = 0.008; n = 175, NOS: poor). Study methodologies were heterogenous (e.g., inconsistent definitions of inactive), with habitual physical activity measured through interviews, patient records, or questionnaires in 14 of 16 studies (NOS rating: poor to fair). Available evidence suggested that physical inactivity and sedentary behaviour were associated with an increased risk of DFU. Further research is needed to develop thresholds for physical inactivity and sedentary behaviour to reduce DFU risk.
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Cardiovascular side effects are commonly reported by men who use anabolic-androgenic steroids (AAS), yet little is known about the factors that increase risk. This study examines data from the 2024 Global Drug Survey (GDS2024) to identify whether route of administration (ROA), image-and performance enhancing drug (IPED) polypharmacy and licit substance use are associated with self-reported cardiovascular-related concerns. The dataset comprised 1167 males (≥16 years) who had used AAS within the previous 12 months. Descriptive statistics summarized demographic and substance use characteristics. Chi-square tests explored associations between self-reported cardiovascular side effects and ROA (oral vs injectable), IPED polypharmacy, and licit substance use respectively. Independent predictors were identified through multivariable binary logistic regression. Associations between substances were investigated using pairwise models. Visualizations included heatmaps, bar charts, forest plots, trend stability, and performance comparisons across models. Showed that, among AAS consumers, 35.7% reported a self-reported cardiovascular-related concern. Alcohol (79.4%), tobacco (42.0%), and E-cigarette use (40.5%) were prevalent among AAS consumers. Clenbuterol use differed significantly by ROA, reported by 28.4% of oral and 24.3% of injectable AAS consumers. Injectable AAS use was strongly associated with concurrent human hormone growth (HGH) and insulin use. In adjusted models, injectable AAS use showed the strongest association with self-reported cardiovascular-related concerns (OR = 10.57, P < .001), followed by oral AAS use (OR = 1.92, P < .001) and clenbuterol use (OR = 1.44, P = .044). Age, HGH, insulin, alcohol, tobacco, and e-cigarette use were not significantly associated with cardiovascular-related concerns. Pairwise analyses indicated that clenbuterol-containing substance combinations were associated with higher odds of reporting cardiovascular-related concerns, highlighting the relevance of ROA and patterns of concurrent substance use. Negative cardiovascular health concerns among AAS consumers are most strongly associated with oral routes and use of substances like clenbuterol.
Total Ankle Arthroplasty (TAA) has evolved into a reliable treatment option for end-stage ankle osteoarthritis; however, wound healing complications remain a significant concern, particularly with traditional anterior approaches. These complications are largely related to the vulnerability of the anterior soft-tissue envelope and may negatively affect early outcomes. The purpose of the present study was to evaluate the safety and early clinical outcomes of a curvilinear anterolateral approach for TAA, with particular focus on wound healing and soft-tissue complications. A retrospective observational study was conducted on 48 consecutive patients undergoing TAA between January 2023 and December 2025. A total of 49 ankle arthroplasties were performed using a curvilinear anterolateral approach. Patient demographics, comorbidities, and perioperative variables were recorded. Primary outcomes included wound-related complications and time to complete healing. Secondary outcomes included functional improvement assessed using the Foot and Ankle Outcome Score (FAOS). Three patients (6.1%) developed wound-related complications. Two patients (4.1%) experienced superficial wound dehiscence, which resolved with conservative treatment. One patient (2.0%) developed a deeper wound complication involving the soft tissues without prosthetic involvement; this case occurred in a high-risk patient with multiple comorbidities and was successfully managed with advanced wound care. No cases of deep prosthetic infection were observed. All remaining cases (93.9%) achieved uneventful wound healing within 12 to 21 days. Functional outcomes showed a significant improvement, with mean FAOS increasing from 40 ± 5 preoperatively to 75 ± 5 at final follow-up. The curvilinear anterolateral approach for TAA demonstrated a low rate of wound-related complications and consistent early functional improvement. By preserving the tibialis anterior tendon sheath and optimizing incision placement, this technique may reduce both vascular and mechanical risk factors associated with wound healing disorders. It represents a safe and reproducible alternative to traditional anterior and transfibular approaches, particularly in patients at increased risk for soft-tissue complications.
Childhood exposure to intimate partner violence (CEIPV) is a pervasive adverse childhood experience with wide-ranging mental health consequences, yet its associations with mental health problems remain inconsistent across studies. Existing meta-analyses are dated and have largely overlooked outcomes beyond childhood. This study employed a three-level meta-analysis to examine the magnitude of the association between CEIPV and mental health outcomes, as well as potential moderators. A systematic search yielded 36 eligible studies (78 effect sizes; N = 59,561). Based on variations in clinical specificity and outcome labels used across studies, outcomes were classified as internalising problems, depressive symptoms, and PTSD-related symptoms. Results revealed a significant moderate overall effect (r = 0.263). The association was significant across internalising problems (r = 0.252), depressive symptoms (r = 0.227), and PTSD-related symptoms (r = 0.319). Moderation analyses indicated that higher study quality and larger sample sizes were associated with smaller effect sizes, and these patterns also applied to the depressive symptoms and internalising problems subgroups, respectively. Studies using the Conflict Tactics Scale showed larger effect sizes compared to studies using other measures. In addition, older participant age was associated with slightly larger effect sizes in the PTSD-related symptoms subgroup. These findings indicate that CEIPV confers significant mental health risks, underscoring the need for trauma-informed prevention and intervention efforts.
Age-related senescence can profoundly alter the physiology and therapeutic potential of cardiac progenitor cells (CPCs), thus undermining the efficiency of cell-based therapies for treatment of various cardiovascular diseases. In this study, CPCs were isolated from right atrial appendage tissue obtained during open heart surgery from patients: younger (< 30 years, n = 10) and elderly (> 60 years, n = 10). Phenotypic and functional characterization of CPCs was done along with evaluation of age-related senescent changes using various assays. CPCs derived from elderly patients exhibited significantly reduced proliferative potential, enlarged morphology, increased expression of senescence markers (p16Ink4A, SA β-gal, γH2AX), and significantly higher proportion of cells in the G0/G1 phase of the cell cycle. In addition, aged CPCs showed elevated secretion of senescence associated secretory phenotypes (SASP) factors, particularly IL-8, IL-10, and IFN-γ. Current study observed that a significantly higher (80%) number of CPCs among the older population were senescent, dysfunctional, and in the resting phase of the cell cycle, thus having limited ability to repair the damaged heart. Further, we observed a contradictory increase in Nkx2.5 expression with age, suggesting the reactivation of the cardiac Nkx2.5 enhancer.
Neuropathic pain (NP) continues to be a significant clinical issue because the existing treatment modalities have very low efficacy and tolerability. An increasing body of mechanistic and translational data is identifying the endocannabinoid system (ECS) as a key regulator of nociceptive transmission, neuroinflammation, and maladaptive synaptic plasticity. This review critically synthesizes preclinical actions, pharmacological variety, and clinical trial evidence supporting cannabinoid-based interventions to NP, alongside identifying translational challenges, safety concerns, and emerging precision- medicine strategies. The approach adopted was a narrative review approach. To identify the relevant literature, published within the last two decades, PubMed, Scopus, Web of Science, Google Scholar were searched using the keywords that are related to cannabinoids, endocannabinoid system, neuropathic pain, phytocannabinoids, and clinical trials. Relevance was used to select preclinical, mechanistic, and clinical studies. The article is written in the form of a narrative review and is not organized in the system of a systematic review. The preclinical evidence demonstrates that cannabinoids regulate NP by acting through CB1- and CB2-mediated, inhibitory effects on the release of neurotransmitters, central sensitization, neuroinflammation and regulation of transient receptor potential (TRP) channels. Phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as synthetic cannabinoids, are effective in various experimental NP models. Clinical trials report variable but clinically significant decreases in the intensity of pain, sleep disturbance, and allodynia; although results vary depending on formulation, dose, route of administration, and heterogeneity of patients. Safety data show dose-related adverse effects, such as dizziness, cognitive impairment, and psychoactive effects, with CBD showing a relatively positive tolerability profile. Although there is a high level of mechanistic support, the translation to consistent clinical benefit is still limited due to pharmacokinetic variability, variation in the ratio of THC:CBD, and patient-specific factors. Other issues are standardization of formulations, safety testing in the long term, and variability in regulations. The varied actions of cannabinoids on NP pathophysiology, through CB1/CB2 agonism, neuroinflammation suppression, and TRP modulation, are strongly supported by preclinical evidence, but are hampered by pharmacokinetic variability, inconsistent THC: CBD ratios and inconsistent patient response. CBD has a good tolerability despite the challenges such as regulatory barriers and lack of long-term safety evidence, which highlights the potential of CBD in precision tactics. To enhance the reliability of treatments, our findings demonstrate that the same delivery mechanisms and tailor-made dosages are needed. Cannabinoids are a promising but emerging treatment option of neuropathic pain. Despite the strong preclinical evidence, the clinical outcomes are still heterogeneous. The future research should focus on optimizing cannabinoid-based therapies compositions, designing better delivery systems, and conducting a long-term safety evaluation to fully realize the translational potential of cannabinoid-based therapies in the management of NPs.
Aging is a relentless process of gradual physio-biochemical non-reversible deterioration that significantly influences human health, leading to declining cellular function and increasing cellular damage; it is recognized as a major risk factor for atherosclerosis and cardiovascular (CV) disease (CVD), the leading cause of death worldwide. Although aging is inevitable, healthy aging is the key to well-being. Longevity is a desirable yet complex outcome influenced by a wide range of factors, including genetics, lifestyle choices, healthcare access, socio-economic conditions, and other environmental factors. The compromised efficiency of processes that counteract age-associated molecular damage affects CVD susceptibility and expedites the emergence of clinical disease. Recently recognized key resilience mechanisms related to aging may constitute new potential therapeutic targets. Geroscience focuses on the discovery and translation of methods and interventions to curtail or reverse age-related deficits that compromise quality of life for older individuals. The geroscience paradigm, increasingly acknowledged in medical specialties, renders possible the prevention of premature aging, the optimal treatment of geriatric diseases, the reduction of healthcare disparities and prejudices, and the extension of the population's health span. These important geroscience issues, including multimorbidity, frailty, tendency to frequent falls, cognitive and multisensory impairment, cardiac arrhythmias, coronary disease and heart failure, as well as undernutrition, sarcopenia and polypharmacy, are herein discussed, together with recent relevant medical advances. Emphasis is placed on boosting psychology and also on pharmacological and nonpharmacological interventions such as exercise and physical activity, healthy diets and lifestyle that target key components of aging, which might assist in both primary (geroprotection) and secondary prevention (gerotherapeutics) of CV and other diseases posing an enormous challenge in older age. The geroscience paradigm is increasingly recognized in medical specialties, enabling the prevention of premature aging, optimal management of geriatric ailments, reduction of health-care disparities and prejudices, and potential improvement of the population's health-span.
The human microbiome is a dynamic and diverse community of microorganisms that affects susceptibility to illness and promotes wellness. Dysbiosis, or disruption of this delicately regulated microbial ecology, has been identified as a major factor in the emergence and development of systemic and organ-specific disorders. With an emphasis on dysbiosis-driven illness processes and therapeutic intervention implications, this study attempts to critically analyze host-microbiome interactions across key human organ systems. Using predetermined microbiome-related keywords, a systematic literature search (2001-2025) was carried out in PubMed, Scopus, Web of Science, and Google Scholar. To assess microbiome formation, organ-specific distribution, disease correlations, and therapeutic implications, English-language peer-reviewed original papers, meta-analyses, and clinical or validated animal studies were chosen and methodically compiled. Microbiome dysbiosis is linked to cardiovascular, metabolic, inflammatory, neurological, hepatic, renal, and cancer-related illnesses by interfering with immune modulation, metabolic balance, and epithelial barrier integrity, according to evidence from human and verified animal research. Modified production of short-chain fatty acids, immunological signaling imbalance, chronic inflammation, and communication between the gut-organ axis are examples of mechanistic linkages. Immune and metabolic indicators improved condition-specifically with interventions such as probiotics, fecal microbiota transplantation, and diet-based regulation. Collectively, current evidence supports the microbiome as a modifiable determinant of disease risk and therapeutic response, underscoring its translational potential for precision medicine.
This study investigated the expression profile of Thrombospondin-4 (THBS4) in intervertebral disc degeneration (IDD) and clarify its regulatory role in lipopolysaccharide (LPS)-induced apoptosis and inflammation in nucleus pulposus cells (NPCs) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. IDD-related differentially expressed genes were screened through the integration of GeneCards and the Gene Expression Omnibus (GEO) database (GSE186542), followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore potential signaling mechanisms. An in vitro inflammatory injury model was established using LPS-stimulated NPCs. The effects of THBS4 overexpression on cell proliferation, apoptosis, inflammatory cytokine secretion, and extracellular matrix protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Additionally, the involvement of the PI3K/AKT pathway in mediating THBS4-related effects was confirmed using the PI3K inhibitor LY294002. Bioinformatics analysis revealed that THBS4 was significantly downregulated in IDD and was closely linked to the PI3K/AKT pathway. Functional assays demonstrated that overexpression of THBS4 markedly enhanced NPCs proliferation, suppressed apoptosis, reduced the secretion of tumour necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6, and increased the expression of IL-10, Aggrecan, and Collagen type II. These protective effects were accompanied by activation of the PI3K/AKT pathway and were significantly reversed by LY294002 treatment. THBS4 alleviated LPS-induced damage in NPCs through the activation of the PI3K/AKT pathway, exerting anti-apoptotic and anti-inflammatory effects; the specific upstream molecular mechanism of PI3K/AKT activation by THBS4 requires further investigation. These findings suggested that THBS4 may serve as a potential therapeutic target for IDD treatment.
We compared the long-term outcomes of endoscopic submucosal dissection (ESD) with those of surgery in late older adult patients aged ≥75 years with early gastric cancer (EGC) who met the curative resection criteria. This multicenter retrospective study included 4,241 older adults with EGC who were treated with either ESD (n=4,083) or surgery (n=158) at 22 hospitals between 2010 and 2020. Overall survival (OS) and gastric cancer (GC) recurrence were investigated in the overall cohort and a 4-to-1 propensity score (PS)-matched cohort. During a median follow-up of 6.6 years, the 5-year OS rates were 84.8% and 82.9% in the ESD and surgery groups, respectively, and OS did not differ between the 2 groups in the overall (P=0.396) and PS-matched cohorts (P=0.248). In the PS-matched cohort, the multivariate analyses showed that overall mortality after ESD (adjusted hazard ratio, 0.77; 95% confidence interval, 0.57-1.04) did not increase compared to that after surgery. The GC recurrence rate after ESD was higher than that after surgery (6.1% [248/4,083] vs. 0.6% [1/158]; 5-year rate: 9.3% vs. 0.7%, respectively; P<0.001 for the overall and PS-matched cohorts). However, approximately 77% (190/248) of the recurrences in the ESD group were metachronous, most of which were successfully managed with endoscopic treatment. The ESD group had fewer adverse events (AEs, 7.6% vs. 12.0%; P=0.044) than the surgery group, and no ESD treatment-related deaths were observed. In late older adult patients (aged ≥75 years) with EGC, long-term outcomes after ESD were comparable to those after surgery for EGC meeting the curative resection criteria, with acceptable treatment-related AEs.
Genome-wide association studies continue to recruit larger samples, increase resolution, and improve their statistical foundations. These investigations often remain restricted by design to large, outbred populations. This can exclude genetically distinct populations, to whom the genetic insights gained may not apply, and forgoes the benefits that isolated populations can offer to biomedical research. Metabolic Syndrome (MetS) is a collection of highly correlated risk factors that predisposes individuals to type 2 diabetes, cardiovascular disease, and chronic kidney disease. The environmental factors that lead to MetS are well understood, but each person's response to these influences is modulated by their genetics. In this mini-review, we discuss the features of population isolates for mapping disease genes, briefly consider some of the clinical aspects of MetS, and compare the recent contributions to understanding the genetic causes of MetS by population isolates and by large open-population approaches. Studies in isolated populations have revealed novel genetic associations, including determining causal variants. Isolated populations have also validated and refined associated loci discovered in large, open populations. Much progress has been made uncovering the genetic basis of MetS and related conditions. However, while the field progresses, the definition of the syndrome remains contested, and a comprehensive understanding of MetS genetics remains elusive.
While personal recovery is a well-established concept for people with mental illness, its application to carers, who share a similarly demanding journey, remains underexplored. This cross-sectional study firstly applied the CHIME framework (Connectedness, Hope and optimism, Identity, Meaning in life, and Empowerment) to 333 carers of children and young people with mental illness in China, via an online survey from September 2024 and February 2025, and aimed to provide baseline data on personal recovery and its correlates in this population. Carers completed questionnaires on demographic, caregiving and illness-related information, five indicators of personal recovery, and three indicators of psychological wellbeing. Latent profile analysis, descriptive analysis, bivariate analysis, and ordinal logistic regression were conducted using SPSS 26.0 and Mplus 8.3. Three profiles of personal recovery were identified: struggling group (13.2%), progressing group (62.4%), and recovering group (24.3%). Bivariate analyses showed that care recipients' sex, carers' employment, illness duration, and SDQ prosocial, externalising, and internalising domains differed significantly across profiles. Ordinal logistic regression (adjusting for all factors) revealed that carers' sex, care recipients' sex, and SDQ prosocial and internalising domains were independently associated with profile membership. Carers in the struggling group had the poorest psychological wellbeing, followed by the progressing and recovering groups. These findings may help identify carers with poor recovery and inform interventions tailored to profile membership. CHIME-based approaches targeting stigma reduction and enhancement of hope and mastery may be related to better personal recovery and psychological wellbeing in this population.
Breast cancer metastasis is one of the leading causes of cancer-related mortality in women, which occurs through an intricate molecular network and cellular events. Over time, lncRNAs have emerged as an important regulator of metastatic progression. These RNAs affect important processes including EMT, ECM remodelling, angiogenesis, immune evasion, and can-cer stemness. LncRNAs regulate this process by acting as molecular decoys, scaffolds, guides, or competing endogenous RNAs, thereby controlling gene expression at both transcriptional and post-transcriptional levels. Various lncRNAs, including HOTAIR, BCAR4, and LINC00511, are known to promote metastasis by driving chromatin remodelling and activating pro-tumorigenic signalling pathways. In contrast, lncRNAs such as GAS5, LINC01133, and TINCR act as metas-tasis suppressors, thereby limiting tumor spreading. A wide range of experimental approaches, including CRISPR/Cas9, RNA interference, in-vitro functional assays, in-vivo models, and bio-informatic analyses, have helped define critical lncRNA-driven regulatory networks. Despite these advances, challenges related to lncRNA conservation, delivery strategies, and context-spe-cific functions persist. Nevertheless, progress in RNA therapeutics and multi-omics technologies is steadily advancing the integration of lncRNA signatures into liquid biopsies, diagnostics, and precision medicine approaches for metastatic breast cancer.
Extreme hot weather poses increasing risks to mental health. Yet, factors affecting vulnerability are under-researched. This mixed-method study integrates a systematic review and qualitative investigation to identify risk and protective factors for heat-related mental health issues, leading to the co-development of a screening tool. This could inform future research and, pending validation in clinical settings, support mental health professionals in assessing vulnerability among service users. We searched PubMed and Web of Science for publications on extreme heat, mental health, and risk/protective factors. In addition, we conducted six focus groups with 21 people with lived experience of heat and/or mental illness and 12 healthcare professionals. Transcripts were analyzed using thematic content analysis and informed the co-development of the screening tool. Out of 764 articles identified by the systematic review, 47 were included. Evidence emerged for age, sex, existing mental illness, ethnicity, and socioeconomic status as risk factors. However, findings were inconsistent between studies, likely due to differences in study population and methodology. Protective effects included good physical health, social support, and exposure to green spaces. Our qualitative investigation identified additional risk and protective factors related to: (1) behavioral adaptability, (2) personal heat sensitivity, and (3) disparities in heat exposure. The resulting screening tool, HEAT-MH (Heat Exposure Assessment Tool for Mental Health), contains 15 questions on previous experiences of heat, general health, and lifestyle. The mental health impacts of extreme heat depend on a range of risk and protective factors, including demographic, socioeconomic, health, and lifestyle characteristics.