Search Results (6,672)

Myocardial infarction with non-obstructive coronary arteries (MINOCA) accounts for approximately 5–15% of all myocardial infarctions and disproportionately affects women. Once treated as a diagnosis of exclusion, MINOCA is now recognised as a heterogeneous, mechanism-based syndrome encompassing atherosclerotic plaque disruption, epicardial and microvascular vasospasm, microvascular dysfunction, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD). Despite the absence of obstructive disease, it carries substantial morbidity and mortality, underscoring the need for accurate aetiological characterisation and tailored therapy. Our aim is to review the contemporary evidence of the role of advanced imaging modalities—cardiac magnetic resonance imaging (CMR), optical coherence tomography (OCT), intravascular ultrasound (IVUS) and invasive functional testing—in the diagnosis, prognostic stratification, and therapeutic guidance of patients with MINOCA. CMR is the non-invasive reference standard for differentiating true ischaemic MINOCA from non-ischaemic mimics such as myocarditis and Takotsubo syndrome, reclassifying the working diagnosis in up to two-thirds of cases. OCT and IVUS provide intracoronary characterisation of culprit substrates that are invisible via angiography, particularly plaque rupture, erosion, intramural haematoma and SCAD, while acetylcholine and adenosine testing identify endothelium-dependent vasospasm and endothelium-independent microvascular dysfunction respectively. Coronary Computed Tomography Angiography (CCTA) could also play an additional role in the diagnosis of epicardial CAD. Each modality additionally carries independent prognostic value, with abnormal findings consistently linked to higher rates of major adverse cardiovascular events. The recently completed PROMISE trial provided the first randomised evidence that stratified, imaging-guided treatment might have some positive impact on angina status and quality of life compared with empirical standard care. In conclusion, advanced imaging has transformed MINOCA from a diagnosis of exclusion into a mechanism-based syndrome amenable to personalised therapy. Broader integration of these modalities into routine practice, supported by further randomised trials, is needed to optimise outcomes. Full article

Background/Objectives: Loneliness is a major public health concern in later life and may be especially prevalent among older adults living in nursing homes. Evidence from Spain remains limited regarding modifiable correlates of different loneliness dimensions. This study aimed to describe social and existential loneliness among nursing home residents and examine their associations with sociodemographic, institutional, functional, and psychosocial factors. Methods: We conducted a cross-sectional study in Spanish nursing homes using face-to-face structured interviews with residents aged ≥65 years (n = 139). Social loneliness was assessed with the ESTE-II scale and existential loneliness with the existential loneliness subscale of the ESTE-R. Functional dependence was measured with the Barthel Index. Health literacy, locus of control, institutional variables, and suicidality-related items were also collected. Spearman correlations and multiple linear regression models with BCa bootstrapped 95% confidence intervals (5000 resamples) were used. Results: Social and existential loneliness were moderately correlated (ρ = 0.481, p < 0.001). Greater activity engagement was independently associated with lower social (B = −1.105, p < 0.001) and existential loneliness (B = −0.732, p = 0.029). Receiving visits regularly was associated with lower social loneliness (B = −4.083, p = 0.002), but not existential loneliness. Greater functional independence was associated with lower existential loneliness (B = −0.044, p = 0.023). Conclusions: Activity engagement was a consistent correlate across loneliness dimensions, whereas regular visits were mainly related to social loneliness and functional independence to existential loneliness. These findings support feasible long-term care strategies focused on meaningful activities, relational contact, and functional support. Full article

Background/Objectives: Anemia in early childhood remains a key global health issue due to its impact on growth and development. While biological determinants of anemia have been extensively studied, parenting styles remain unexplored. This study aimed to examine the association between parenting styles, anemia, and developmental outcomes among under-five children. Methods: From February to March 2026, a cross-sectional study was carried out in Bandung, Indonesia, involving children aged 6–59 months who visited the Pasirkaliki Primary Health Centre. Anemia was confirmed by laboratory testing, defined as a hemoglobin level ≤ 11 g/dL. The Parenting Styles and Dimensions Questionnaire was used to assess parenting styles, while the Pre-Screening Developmental Questionnaire was used to examine child development. Statistical analyses were performed using the Mann–Whitney U test, Chi-square test or Fisher’s exact test, and logistic regression analysis. Results: One hundred and ninety-three subjects were included in the analysis, among which 20.2% were anemic, with a significantly higher proportion among children aged below 24 months (p < 0.001). Permissive parenting was significantly more common among children with anemia and was associated with higher odds of anemia (aOR = 10.31; 95% CI: 3.92–27.10). Children with anemia had significantly higher odds of developmental delay (aOR = 19.49; 95% CI: 6.46–58.84), after adjustment for child age, maternal education, and family income. Conclusions: Permissive parenting was associated with anemia, while anemia was associated with increased odds of developmental delay in under-five children, highlighting the importance of considering not only biological but also psychosocial factors in early child health interventions. Full article

LGBTQ+ individuals experience disproportionately high rates of mental health challenges, driven largely by exposure to stigma, discrimination, and minority stress. In response, there is growing interest in creative, community-based interventions that support wellbeing. This study evaluates “LGBTQteehee!”, a 10-week stand-up comedy programme designed to promote mental wellbeing and resilience among LGBTQ+ individuals. N = 6 participants took part in post-intervention qualitative data collection via focus group and semi-structured interviews. Data were analysed using Reflexive Thematic Analysis. Two overarching themes were identified: “Standing up Together: A Queer Ensemble” and “Comedy as Catharsis”, each comprising two subthemes. The first theme captured the importance of community, highlighting “Where Comedy Meets Community” and “Where Safety Takes Centre Stage”, emphasising the role of belonging, diversity, and psychological safety. The second theme reflected the transformative potential of comedy, with “Performing (Queer) Resilience” and “Taking the Mic and Owning the Moment” illustrating how participants reframed lived experience into empowering narratives and reported increased confidence and self-expression. Findings suggest that the benefits of the intervention extend beyond humour alone, instead reflecting the interplay between social connection and identity-affirming narrative expression. Participants described how having a space to talk openly about their mental health and receive support from others contributed to their perceptions of both individual and collective resilience. These findings suggest that community-based comedy interventions may offer accessible and identity-affirming spaces through which LGBTQ+ individuals can explore wellbeing, belonging, and resilience. Whilst further evaluation is required, the findings contribute to growing discussions regarding the role of arts-based approaches in supporting LGBTQ+ mental health and wellbeing. Full article

Domestic cats (Felis catus) are ubiquitous companion animals that provide substantial psychological and social benefits to children and adults alike, but they also serve as reservoirs and vectors for a wide range of zoonotic pathogens. Close physical contact between cats and children, frequent use of shared environments such as homes, playgrounds, and sandboxes, and still-developing hygiene behaviours increase opportunities for exposure to protozoa, helminths, bacteria, fungi, and ectoparasite-borne agents. This review synthesizes current evidence on key feline-associated zoonoses of pediatric concern—including Toxoplasma gondii, Toxocara cati, Ancylostoma spp., Dipylidium caninum, Bartonella henselae, Salmonella enterica, Campylobacter jejuni, Pasteurella multocida, Microsporum canis, flea-borne Rickettsia species, and rabies—with emphasis on transmission routes, clinical manifestations, and risk modifiers in children, pregnant women, and immunocompromised individuals. Within a One Health framework, we also summarize global publication trends on feline zoonoses, discuss how urban cat ecology and management (including free-ranging cats in child-frequented environments) may shape pediatric risk, and outline practical prevention strategies centred on hygiene, veterinary care, and targeted education for caregivers and children. Full article

Background: Hypoxic–ischaemic brain injury (HI) is a major contributor to neurological deficits following stroke. Understanding what happens to the smallest functional and structural unit of the central nervous system in the face of oxygen and nutrient deprivation is essential to fully comprehend the pathogenesis of diseases and disorders associated with HI, such as ischaemic stroke. Aim: The aim of this study was to develop a robust in vitro tool for initial screening of potential therapeutics and identification of diagnostic markers of brain hypoxic injury. Methods: This study details and validates a comprehensive protocol for modelling HI using differentiated SH-SY5Y neuroblastoma cells (Neuron-like Cells, NLCs). First, we optimized the differentiation process and confirmed the maturity and purity of NLCs via standard molecular markers. The NLCs exhibited functional excitotoxicity, demonstrating a graded cell death response to N-methyl-D-aspartate (NMDA), thus validating their functional application. To simulate HI, we initially optimized the oxygen-glucose deprivation (OGD) treatment using graded concentrations of CoCl₂ (0.125 mM to 2 mM) in glucose-free media. The validated NLCs were then subjected to the refined OGD protocol (1 mM CoCl₂ in glucose-free media) for 3 h, followed by various periods of reoxygenation (1 h, 3 h, 6 h, 12 h, 18 h, and 24 h). Result: Bulk RNA-sequencing revealed a distinct temporal transcriptional response to HI. Injury-associated genes, including heat shock proteins and stress markers, were significantly (p < 0.05) upregulated at 3 h of reoxygenation, peaked at 6 h, and declined thereafter, remaining above baseline at 24 h. Upstream regulator analysis identified IL-1β, TNF-α, and HIF-1α as key drivers during OGD, with additional regulators emerging during reoxygenation. TNF-α and β-oestradiol were consistently identified across time points, while TGF-β1 and NTRK1 became prominent during peak injury and later phases. Analysis of secreted factors showed increased release of inflammatory (TNF-α) and neurotrophic (β-NGF, BDNF, VEGF) mediators with reoxygenation, while maximal cell death occurred at 24 h. Conclusions: This study identifies a transient, time-dependent transcriptional cascade following hypoxic–ischaemic injury, highlighting a critical window for early neuronal response. The model provides a reproducible platform for studying neuronal injury and recovery, and identifies known (TNF-α, IL-β, and HIF-1α), context-specific (NTRK1 and TGF-β) and novel (β-oestradiol) regulators of the injury response with potential relevance for therapeutic targeting. Full article

Vitamin D has long been recognized for its role in calcium homeostasis and bone metabolism; however, it is now emerging as an important regulator of central nervous system (CNS) function. Recent evidence suggests that vitamin D signaling contributes to the pathogenesis and progression of several neurodegenerative disorders. Vitamin D exerts neuroprotective effects through multiple mechanisms, including regulation of calcium homeostasis, modulation of immune responses, reduction in oxidative stress, stimulation of neurotrophic factors, and maintenance of blood–brain barrier (BBB) integrity. Vitamin D receptors and metabolizing enzymes are widely distributed across several brain regions, highlighting their direct involvement in neuronal function. This review summarizes the biosynthesis, metabolism, and signaling pathways of vitamin D. It explores its role in neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury (TBI). Evidence from experimental and clinical studies indicates that vitamin D deficiency is associated with an increased risk and severity of these conditions, while supplementation may provide therapeutic benefits. Full article

Background/Objectives: Community-based drug rehabilitation is a key component of public health strategies in China, with anti-drug social workers playing a frontline role in relapse prevention, social reintegration, and long-term recovery. However, the sustainability and effectiveness of this workforce remain uncertain due to complex organisational and structural conditions. This study aims to examine the professional roles, work-related challenges, and coping strategies of anti-drug social workers within community-based rehabilitation systems. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and was registered in PROSPERO (Registration ID: 1381833). The literature published between 2009 and 2025 was identified through Google Scholar, PubMed, Web of Science, and the Electronic Library. A total of 35 Chinese and English-language studies met the inclusion criteria and were analysed to synthesise evidence on social work practice in drug rehabilitation contexts. Results: The findings identify three core professional roles: information provider, resource linker, and relationship repairer. These roles highlight the multifaceted contribution of social workers in bridging institutional systems and client needs. However, their effectiveness is constrained by fragmented governance structures, role conflict, professional identity ambiguity, administrative burden, limited training, and sustained emotional labour. These conditions contribute to occupational stress, burnout risk, and workforce instability, which weaken service continuity and client-centred care. Conclusions: Strengthening community-based drug rehabilitation requires addressing workforce and system-level constraints. Clearer role definition, targeted interdisciplinary training, reduced administrative demands, and structured organisational support are essential to enhance professional capacity, improve service delivery, and support long-term recovery outcomes. Full article

Background: Although single-inhaler triple therapy (SITT) improves COPD control, the specific structural and behavioral predictors of short-term clinical response following therapeutic simplification remain incompletely characterized. Methods: This prospective, multicenter observational study (N = 684) evaluated patients switching from triple therapy regimens involving multiple inhalers to SITT. A clinically meaningful response was defined as an intra-individual reduction of ≥2 points in the validated RADAR score at three months. Results: Therapeutic simplification reduced regimens requiring ≥4 inhalations/day from 46.1% to 14.3%, and poor behavioral adherence from 45.2% to 16.6%. Multivariable models identified an observed responder profile: higher baseline RADAR burden was the strongest predictor of improvement (aOR 2.00), whereas severe airflow limitation (FEV₁ < 50%) attenuated the response. Exploratory mediation analysis indicated that 88.6% of the observed clinical stabilization was not explained by measured adherence changes, and may therefore also encompass unmeasured behavioral, educational or device-related factors. Patients burdened with both high complexity and poor adherence showed the highest rate of combined structural–behavioral improvement (25.0% vs. 4.7% overall). Conclusions: Switching from MITT to SITT was associated with reduced treatment complexity, improved adherence profiles, and short-term improvement in RADAR-defined clinical control. Patients with greater baseline RADAR burden and regimen complexity showed larger observed improvements. Full article

Genetic cardiomyopathies (GCMs) are chronic heart muscle disorders requiring lifelong monitoring and treatment. Although quality of life (QoL) and health-related quality of life (HRQoL) are increasingly recognized as important outcomes in cardiomyopathy care, their conceptualization and measurement remain inconsistent. This scoping review aims to (a) identify the tools most commonly used to assess QoL and HRQoL in adults with genetic cardiomyopathies and (b) map the thematic areas of existing studies, including symptom burden, psychological distress, diagnostic challenges, and the impact of medical and psychological interventions. PubMed, Scopus, and PsycINFO were systematically searched, and the final search was completed in November 2025. Seventeen peer-reviewed studies met the inclusion criteria and were included in this scoping review. The review followed the PRISMA extension for Scoping Reviews and included both quantitative, qualitative and mixed-methods designs. Most studies employed standardized tools such as EQ-5D (N = 5), SF-36/SF36v2 (N = 5), and the Kansas City Cardiomyopathy Questionnaire (N = 3), while others included the Minnesota Living with Heart Failure Questionnaire (N = 2) and disease-specific or ad hoc measures. The most frequently investigated themes included impairments in physical functioning, emotional well-being, symptom burden, psychological distress, and social participation. Several studies showed that patients’ perceived QoL was more closely associated with symptom burden and psychological adjustment than with objective clinical indicators alone. Clinical interventions showed mixed or limited effects on QoL and HRQoL outcomes, even when clinical parameters improved. Qualitative research further emphasized the lived experiences of patients and families, highlighting unmet needs in care. Less commonly addressed findings concerned caregiver perspectives, patient–provider communication, treatment adherence, socioeconomic disadvantage, healthcare costs, productivity loss, and the experiences of patients with rarer cardiomyopathy-related conditions. The results highlight how QoL and HRQoL are central but still inconsistently assessed outcomes in cardiomyopathy research. This review calls for greater conceptual clarity between QoL and HRQoL, greater standardization in measurement tools, broader inclusion of psychosocial variables, and more patient-centred research approaches to better support individuals living with cardiomyopathies. Full article

Background: Para-aortic lymph node involvement is present in approximately 17–24% of women with locally advanced cervical cancer (LACC) and is one of the strongest adverse prognostic factors in this population. Current international guidelines recommend two alternative staging techniques: the International Federation of Gynecology and Obstetrics (FIGO) and European Society of Gynecologic Oncology (ESGO) endorse imaging-based staging as the primary method to define radiation fields, whereas the National Comprehensive Cancer Network (NCCN) lists pre-treatment minimally invasive para-aortic lymphadenectomy as a Category 2B recommendation. Objective: We aimed to review and critically appraise the available evidence on the oncologic impact (progression-free and overall survival) of pre-treatment surgical para-aortic staging compared with clinical imaging-based staging in women with LACC. Methods: We searched MEDLINE (Ovid), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Scopus from inception to January 2026, complemented by manually searching the reference lists for relevant articles and prior reviews. The review focused on comparative studies of women with LACC of squamous, adenocarcinoma, or adenosquamous histology—operationally defined as FIGO 2009 stages IB2–IVA with pelvic nodal involvement or FIGO 2018 stages IB3–IVA who received definitive-intent radiotherapy with or without concurrent chemotherapy and brachytherapy, and for whom comparative survival outcomes between a surgical-staging arm and an imaging-staging arm were reported. For this manuscript, a narrative review style was planned and reported in line with SANRA (Scale for the Assessment of Narrative Review Articles) quality criteria. Results: Twelve studies were included: two randomized controlled trials and ten observational studies (nine retrospective cohorts and one population-based analysis). Surgical staging consistently increased detection of occult para-aortic disease and led to more frequent use of extended-field radiotherapy (18–44%), but it did not yield a reproducible advantage in terms of progression-free or overall survival over imaging-guided chemoradiation. Conclusions: In LACC, pre-treatment surgical para-aortic staging improves anatomic and prognostic information but has not shown a consistent survival advantage over imaging-based staging combined with contemporary chemoradiation. Current comparative evidence does not support routine surgical staging, and its use still warrants further prospective evaluation in large clinical trials. Until results from ongoing phase III trials are available, surgical staging should be considered an individualized option in highly selected cases within multidisciplinary decision-making at experienced clinical centers. Full article

Background: Metabolic control in phenylketonuria (PKU) is known to deteriorate with age, but national-level data describing blood phenylalanine (Phe) control across the United Kingdom (UK) are limited. Objective: To characterise blood Phe control in individuals with PKU attending UK metabolic centres. Methods: Sixteen UK centres (nine paediatric, six adult, one mixed) retrospectively extracted blood Phe results collected between 2012 and 2018. Demographic, phenotypic and monitoring-related variables were analysed. Written consent for data collection was obtained from all patients or their caregivers. Results: Data were available for 871 individuals (55% female), of whom 744 (85%) were classified as follows: classical PKU, 75%, mild PKU, 22% and hyperphenylalaninaemia, 3%. Mean blood Phe concentrations were significantly higher in adults than children (491 ± 308 vs. 303 ± 199 µmol/L; p < 0.001), and the proportion of samples within target range declined steadily with age, from 78% in children <2 years to 36% in adults ≥41 years. Individuals with classical PKU had higher mean Phe concentrations and lower target attainment than those with HPA (386 vs. 300 µmol/L; 61% vs. 78%; p < 0.001), while mild PKU and HPA showed comparable control. Females generally demonstrated better metabolic control than males. More frequent dried blood spot sampling for blood Phe was strongly associated with improved metabolic control: weekly (254 ± 175 µmol/L; 82% within target), fortnightly (319 ± 207 µmol/L; 70%), monthly (397 ± 231 µmol/L; 61%), and less than monthly (624 ± 349 µmol/L; 44%). Nearly half of the blood Phe samples (47%) with recorded timing were taken in a non-fasting state. Conclusions: Achieving lifelong metabolic stability on a Phe-restricted diet alone remains challenging. These national data highlight the need for broader therapeutic options to support individuals with PKU across the lifespan. Full article

Cutaneous Melanoma is a biologically heterogeneous malignancy. Although recent therapeutic advances have improved survival, durable remissions remain elusive for many patients. Surgical excision with stage-appropriate margins and selective nodal staging remains the cornerstone of curative-intent management. In contrast, conventional cytotoxic chemotherapy now plays a limited, largely palliative role given its modest efficacy and substantial toxicity. Targeted therapy with BRAF/MEK inhibitors has improved outcomes in patients with BRAF V600-mutant melanoma, resulting in rapid tumor regression and meaningful survival benefits. However, long-term disease control is frequently compromised by adaptive resistance, commonly driven by MAPK pathway reactivation or compensatory PI3K/AKT signaling. In parallel, immune checkpoint inhibitors targeting PD-1, CTLA-4, and emerging pathways have reshaped treatment across disease stages, enabling deep and sometimes durable responses. Despite this progress, primary and acquired resistance, as well as acute and chronic immune-related toxicities, continue to pose significant clinical challenges. Current therapeutic strategies focus on rational combinations of targeted therapy, checkpoint blockade, IL-2-based approaches, oncolytic viruses, and adoptive cell therapies such as tumor-infiltrating lymphocytes to enhance response depth and durability. However, these intensified regimens carry increased toxicity risks, highlighting the need for improved patient selection and monitoring. Overall, emerging evidence supports a paradigm shift toward optimized treatment sequencing, response-adapted surgical strategies, and biomarker-guided personalization to maximize clinical benefit while minimizing toxicity. Full article

Rising cancer incidence and survival rates have led to an unprecedented demand for psychosocial care. Yet, limited financial and practical resources present a barrier to the provision of evidence-based care. Clinical practice guidelines (CPGs) are well-positioned to enhance the quality and efficiency of psychosocial oncology care; however, little is known about their use and perceptions in the field. The present study explored the use and perceptions of CPGs among 172 Canadian psychosocial oncology clinicians via a cross-sectional, online survey. Findings revealed substantial variation in awareness, with over 20% of participants reporting no familiarity with CPGs, and low to moderate use of CPGs (M = 2.97, SD = 2.96) among users. Key barriers included a lack of formal training, limited applicability to local contexts, and systemic constraints such as high workloads. Conversely, participants highly endorsed facilitators, including accessible training programs, relevant tools/interventions, and greater institutional and community engagement. Clinician perspectives are paramount to the dissemination and implementation of psychosocial oncology CPGs. Our findings suggest that successful implementation requires broader accessibility, widespread adaptation, and greater community engagement. By addressing these systemic constraints, CPGs may be better positioned to bridge the gap between evidence and real-world service provision. Full article

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy characterized by variable clinical behavior and diverse molecular phenotypes. Although immune checkpoint inhibitors and targeted therapies have transformed the treatment landscape of advanced RCC, clinically validated biomarkers capable of improving risk stratification, therapeutic-decision making and disease monitoring remain lacking. Kidney injury molecule-1 (KIM-1), also known as hepatitis A virus cellular receptor-1 (HAVCR1) or T-cell immunoglobulin and mucin domain-containing protein-1 (TIM-1), has emerged as a biologically compelling investigational biomarker e because of its close relationship to proximal tubular epithelial injury and renal carcinogenesis. KIM-1 is a transmembrane glycoprotein minimally expressed in normal kidney tissue but markedly upregulated in dedifferentiated proximal tubular epithelial cells following injury, and in clear cell RCC, where its extracellular domain can be shed into plasma and urine. Beyond its role as a marker of tubular injury, KIM-1 participates in immune regulation, phagocytosis, inflammatory signaling and tissue remodeling, supporting its potential relevance to tumor biology. Clinical studies have demonstrated associations between elevated circulating KIM-1 levels and RCC diagnosis, recurrence risk, and survival outcomes, particularly in localized and postoperative disease settings. KIM-1 has additionally been investigated as a therapeutic target through antibody–drug conjugate approaches. Despite promising translational data, important limitations yet remain. Current evidence is predominantly prognostic rather than predictive, and substantial analytical and biological challenges continue to limit implementation. Assay standardization, clinically meaningful cutoffs, specimen selection, timing of sampling, and confounding by chronic kidney disease or nonmalignant renal injury remain incompletely resolved. Furthermore, evidence supporting incremental value beyond established clinicopathologic models remains limited. This review critically evaluates the biological rationale, analytical considerations and clinical evidence supporting KIM-1 in RCC. Particular emphasis is placed on distinguishing prognostic, predictive, pharmacodynamic, and therapeutic applications, as well as defining the evidentiary gaps that must be addressed before clinical implementation. Current evidence is derived predominantly from retrospective and exploratory analyses, and important limitations remain regarding assay standardization, biological specificity, chronic kidney disease-related confounding, and prospective validation. The review concludes with a summary of the evolving landscape of KIM-1-directed biomarker strategies in RCC, which may ultimately contribute to improved biologic risk stratification and biomarker-driven clinical investigation in RCC. Full article