Search Results (444)

Biomarker-based prevention is rapidly expanding, driven by advances in molecular diagnostics, genetic profiling, and commercial direct-to-consumer (DTC) testing. General practitioners (GPs) increasingly encounter biomarker results of uncertain relevance, often introduced outside the guideline frameworks. This creates new challenges in interpretation, communication, and equitable resource use in primary care. This narrative review synthesizes evidence from population-based studies, guideline frameworks, consensus statements, and communication research to evaluate the predictive value, limitations, and real-world implications of biomarkers in asymptomatic adults. Attention is given to polygenic risk scores, DTC genetic tests, neurodegenerative and cardiovascular biomarkers, and emerging multi-omics and aging markers. Several biomarkers, including high-sensitivity cardiac troponins, N-terminal pro–B-type natriuretic peptide, lipoprotein(a), coronary artery calcium scoring, and plasma p-tau species, showed robust predictive validity. However, many widely marketed biomarkers lack evidence of clinical utility, offer limited actionable benefits, or perform poorly in primary care populations. Unintended consequences, such as overdiagnosis, false positives, psychological distress, diagnostic cascades, and widening inequities, are well documented. Patients often misinterpret unvalidated biomarker results, whereas DTC testing amplifies demand without providing adequate counseling or follow-up. Only a minority of biomarkers currently meet the thresholds of analytical validity, clinical validity, and clinical utility required for preventive use in general practices. GPs play a critical role in contextualizing biomarker results, guiding shared decision-making, and mitigating potential harm. The responsible integration of biomarkers into preventive medicine requires clear communication, strong ethical safeguards, robust evidence, and system-level support for equitable, patient-centered care. Full article

Introduction: Palliative needs assessment and referral to advanced palliative care resources are fundamental aspects of complex chronic patients’ care. Primary care Nurse Case Managers play a key role in the care of these patients. Objective: We aimed to describe the experiences of primary care Nurse Case Managers in palliative care needs identification and complex chronic patients’ referral to advanced palliative care resources. Method: This is a qualitative descriptive study with a phenomenological approach. Semi-structured online interviews were conducted with primary care Nurse Case Managers. A thematic analysis was performed using ATLAS.ti software. Results: 20 nurses participated, 16 of whom were women, with a mean age of 52.3 years and an average of 15.9 years of experience in primary care. Regarding “Palliative care Needs Assessment”, four sub-themes have been identified: “What do you understand?”, “How do you assess?”, “Difficulties” and “Alternatives” to current palliative care needs assessment. For the “Palliative Care Referral” theme four sub-themes have been identified: “Criteria”, “Tools”, “Difficulties” and “Alternatives” for referral. Discussion: Palliative needs are identified in patients with incurable diseases when there are no curative treatment options and when quality of life must be prioritized. Symptoms, general condition, progression, and comorbidity are assessed. Open interviews and home visits are essential for assessing the social and family context and the home resources available. Barriers identified include the conspiracy of silence, limited training in non-oncological palliative care, and a lack of staff and caregiver’s understanding of illness situation. The presence of difficult symptoms and a limited life expectancy were identified as key criteria for referral to palliative care. The physician’s assessment, the family’s request, and consultation with specialized teams play a key role in prognosis. Barriers include late referrals, lack of a palliative background, inequity in access to resources, and low visibility of the palliative care needs of non-cancer patients. Conclusions: Significant challenges remain in identifying palliative needs and referral to specialized resources, highlighting the need to optimize resources, strengthen professional training, and improve coordination between levels of care to ensure quality palliative care. Full article

The present review aims to provide a comprehensive overview of the current literature on Adams–Oliver syndrome (AOS), synthesizing information on its clinical features, genetic and molecular underpinnings, nutritional aspects, and key nursing care considerations. AOS is a rare congenital disorder. Its genetic basis is heterogeneous, involving mutations in at least six key genes (ARHGAP31, RBPJ, NOTCH1, DLL4, DOCK6, and EOGT), which primarily affect vascular development through pathways like Notch signaling and Rho GTPase regulation. The management of AOS is complex and requires a multidisciplinary approach. The clinical presentation of AOS is highly variable, ranging from mild to severe and includes a wide spectrum of clinical manifestations, most notably aplasia cutis congenita and terminal transverse limb defects. The underlying molecular mechanisms predominantly point towards vasculopathy, disrupting embryonic development. Emerging evidence also highlights the presence of nutritional issues, such as poor feeding and growth failure, which are often overlooked. Management demands an integrated, multidisciplinary management approach, requiring coordinated effort from specialists in pediatrics, genetics, molecular biology, cardiology, surgery, and nutrition. Specialized nursing care is crucial for managing complex symptoms, particularly wound care for aplasia cutis, and for providing family support. Full article

Tetanus is a life-threatening neurological disease affecting vertebrate species, including primates. Here, we present a case of severe generalized tetanus in a juvenile male chimpanzee (Pan troglodytes) that was rescued from the illegal wildlife trade and admitted to a rehabilitation center in the Republic of Congo. Upon arrival, the chimpanzee presented with deep, contaminated constrictive wounds, trismus, generalized rigidity, and stimulus-induced tonic spasms accompanied by transient apnea, while remaining conscious. A presumptive clinical diagnosis was made, after which integrated care began immediately. This included meticulous wound debridement and irrigation, passive immunization with antitoxin, initiation of active immunization, metronidazole with adjunctive penicillin G, diazepam-based spasm control, multimodal analgesia, and low-stimulation nursing with oxygen supplementation, enteral nutrition, and temporary urinary catheterization. Aerobic wound culture yielded mixed flora, and a Gram stain of the feces showed large Gram-positive rods with terminal spores. Hematology tests revealed leucopenia with neutropenia and severe thrombocytopenia. The spasms ceased by day 5, at which point the diazepam dose was reduced and oral intake was increased. By week 8, he had made a full clinical recovery and was successfully reintegrated into his group. This case supports the use of pragmatic, sanctuary-adapted protocols and systematic vaccination. Full article

Background and Clinical Significance: Carcinosarcomas are highly aggressive tumors with both carcinomatous and sarcomatous components, typically arising from the female genital tract. Primary retroperitoneal carcinosarcomas are extremely rare, and their occurrence during pregnancy presents major clinical and ethical challenges. Case Presentation: We report a case of a 24-year-old primigravida diagnosed with a large encapsulated retroperitoneal mass at 12 weeks of pregnancy, initially presenting with abdominal pain. The patient declined medical advice for pregnancy termination and chose to continue despite oncological risks. A multidisciplinary team planned delayed surgery after delivery. At 34 weeks, a cesarean section resulted in a healthy newborn, but surgical exploration revealed an inoperable, invasive tumor. The patient died two days later from postoperative complications. Autopsy confirmed widespread tumor invasion and lung metastases consistent with primary retroperitoneal carcinosarcoma. Conclusions: This case highlights the challenges of managing aggressive malignancies during pregnancy, emphasizing early diagnosis, multidisciplinary care, and ethical decision-making while respecting patient autonomy. Full article

ITIC’s superior electron-accepting capacity and efficient oxygen reduction motivated the design of a sensor to enhance sensitivity, selectivity, and stability over conventional oxygen-dependent or fullerene-based systems. As oxygen acts as the terminal reagent in enzymatic glucose oxidation, we developed an ITIC-mediated glucose oxidase (GOx) biosensor on glassy carbon (GCE) and screen-printed carbon electrodes (SPCE). ITIC, a non-fullerene organic semiconductor, was drop-cast onto the electrode to catalyze oxygen reduction, followed by GOx immobilization in a chitosan matrix. Scanning electron microscopy (SEM) confirmed uniform, ultrathin coatings without significant morphological changes upon ITIC and GOx deposition. Electrochemical studies (cyclic (CV) and differential pulse voltammetry (DPV)) revealed a distinct ITIC reduction peak at –0.7 V (vs. Ag/AgCl) and a glucose-dependent current decrease, consistent with mediated electron transfer during enzymatic oxidation. Under optimized conditions, the GCE-based biosensor showed a sensitivity of 10.7 μA L mmol⁻¹, a linear dynamic range (LDR) of 0.10–1.00 mmol L⁻¹, and detection (LOD)/quantification (LOQ) limits of 0.02 and 0.06 mmol L⁻¹, respectively. The SPCE device displayed sensitivity (3.8 μA L mmol⁻¹) and maintained excellent linearity (R² > 0.99) with LOD and LOQ of 0.05 and 0.16 mmol L⁻¹. Both platforms showed good precision (RSD < 5%) and reliable recovery in deproteinized plasma and artificial tears (90–104%). The superior performance of the GCE is attributed to higher ITIC loading, faster electron transfer, and reduced background current, while the SPCE offers a low-cost, disposable format with sufficient analytical performance for point-of-care glucose monitoring. Full article

Background: Gestational guilt is an understudied emotional experience that can affect maternal well-being and prenatal bonding. This study aimed to develop and validate the Pregnancy Guilt Assessment Scale (PGAS) in a sample of Spanish pregnant women, assessing its factorial structure, reliability, and validity. Methods: Four phases were conducted: (1) item generation through focus groups (n = 17) and cognitive interviews (n = 8); (2) expert content validation (n = 3); (3) exploratory factor analysis (EFA) in a pilot sample (n = 85); and (4) confirmatory factor analysis (CFA) and validity testing in an independent sample (n = 171). Additional measures included antenatal depression, prenatal distress, affect, self-esteem, social support, and dispositional guilt. Internal consistency, correlations, and multiple regressions assessed reliability and convergent and incremental validity. Results: The final 16-item PGAS showed a bifactor structure with a general factor and four dimensions: G-LSC (Lack of self-care), G-UEE (Unmet emotional expectations), G-SP (Social pressure), and G-CWR (Conflict with work role). The model demonstrated good fit (χ² = 109.42, df = 88, p = 0.061; CFI = 0.974; TLI = 0.965; RMSEA = 0.069; SRMR = 0.030) and high reliability (α total = 0.96; ω = 0.98; subscales α = 0.90–0.94). PGAS scores correlated positively with dispositional guilt, negative affect, prenatal distress, and antenatal depression. In regressions, G-UEE uniquely predicted depression (β = 0.213, p = 0.002) and G-SP predicted distress (β = 0.303, p < 0.001). Women who had considered pregnancy termination scored higher on guilt (p < 0.001). Conclusions: The PGAS is a reliable and valid instrument for assessing pregnancy-related guilt in Spanish women, with potential relevance for perinatal mental health research and clinical practice, while future studies should evaluate its performance in other cultural settings. Full article

Background/Objectives: This study explored end-of-life care stress, attitudes toward end-of-life care, and end-of-life care performance as predictors of job satisfaction among hospital nurses. Methods: A descriptive cross-sectional design was employed to assess job satisfaction among nurses with end-of-life care experience in tertiary and general hospitals in South Korea. A convenience sample of 215 nurses was recruited. Eligibility criteria included at least 3 months of experience as a direct care nurse and having provided care to terminally ill patients at least once. Data were collected through an online survey. The study variables included end-of-life care stress, attitudes toward end-of-life care, end-of-life care performance, and job satisfaction. Data were analyzed using descriptive statistics, ANOVA, Pearson correlation coefficients, and hierarchical regression analysis. Results: Attitudes toward end-of-life care (β = 0.277, p < 0.001) and end-of-life care performance (β = 0.339, p < 0.001) were significant predictors of job satisfaction, with being enrolled in a master’s nursing program (β = 0.228, p < 0.001) also contributing positively. End-of-life care stress showed no direct association with job satisfaction. The final model explained 29.4% of the variance in job satisfaction (adjusted R² = 0.294). Conclusions: End-of-life care performance was the strongest predictor of job satisfaction, suggesting that nurses’ perceived competence enhances professional fulfillment. Positive attitudes toward end-of-life care further strengthen satisfaction. Continuous education and supportive organizational environments are essential to enhance nurses’ competence, attitudes toward end-of-life care, and quality of end-of-life care. Full article

Background: Terminal ileum inflammation and surgical resections impair absorption of vitamin B12 and D in patients with Crohn’s disease (CD) and Ulcerative Colitis (UC). We assessed differences in subclinical deficiencies of vitamin B12 (<350 pg/mL) or D (<50 nmol/L), by lesion localization (namely non-ileal CD, ileal CD, and UC) and surgical resection status (namely no resection, non-ileal small bowel resections, ileocecal resections, and colonic resections) in CD and UC patients. Methods: We analyzed data from 571 patients (17–93 years), with UC (51%) and CD (49%, including 47 non-ileal (8%), 244 ileal-CD (46%)) managed at the University of Missouri Health Care System (Jan 2017–April 2022). Results: Prevalence of vitamin B12 and vitamin D deficiencies was 19% and 83%, respectively. Prevalence of resection was 26%, including 5% with non-ileal small bowel resections, 11% with ileocecal resections, and 10% with colonic resections. CD with ileal involvement was associated with a 3-fold elevated risk of B12 deficiency (p = 0.004), but not vitamin D. Ileocecal resections were associated with a >3-fold increase in both B12 deficiency (OR = 3.53, p = 0.001) and D deficiency (OR = 3.35, p = 0.044). Conclusions: CD patients with ileal involvement and ileocecal resections have an elevated risk of vitamin B12 and D deficiency, and may benefit from adjunctive supplementation. Full article

Background: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness. Case Presentations: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk. Discussions: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings. Conclusions: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults. Full article

Background and Objectives: Cardiovascular–kidney–metabolic (CKM) syndrome reflects the interconnection between metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Despite increasing awareness, population-based data on CKM syndrome are limited, particularly in Europe. This study assessed the prevalence of CKM syndrome and the use of renal and cardiac biomarkers in Lithuania. Materials and Methods: Health records of 923,329 adults aged ≥40 years from the national Electronic Health Services and Cooperation Infrastructure Information System were analyzed. CKM-associated conditions (prediabetes/type 2 diabetes, obesity, CKD) and cardiovascular outcomes (atherosclerotic CVD, peripheral vascular disease, stroke, heart failure, atrial fibrillation) were identified. CKM stages were defined as stage 0 (no CKM conditions), stages 1–3 (at least one CKM condition), and stage 4 (at least one CVD diagnosis). The use of estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) testing was evaluated. Results: Overall, 34.8% of adults met criteria for stage 4 CKM syndrome, and 23.4% were classified as stage 1–3. Obesity (21.2%) and type 2 diabetes (17.2%) were the most common CKM-associated conditions. Heart failure (25.4%) and atrial fibrillation (14.0%) were the most common cardiovascular outcomes, with ≥2 CVD diagnoses present in 15.4% of patients. Among stage 1–3 patients, eGFR, ACR, and NT-proBNP were measured in 53.5%, 9.0%, and 4.9%, respectively. Conclusions: A third of Lithuanian adults aged ≥40 years had stage 4 CKM syndrome. The underuse of biomarker testing highlights missed opportunities for early detection. Broader implementation of biomarker testing and integrated care is warranted to slow progression of CKM syndrome and reduce cardiovascular risk. Full article

Background/Objectives: Nutrition at the end of life raises many dilemmas. “End of life” refers to the period associated with a progressive incurable disease, with a life expectancy of less than six months, and limited curative treatments. In intensive care units (ICUs), decisions about artificial nutrition and hydration (clinically assisted nutrition and hydration, CANH) are especially complex because patient goals shift from survival to comfort. Nutrition and hydration are often requested by patients and their families, even when clinical benefits are uncertain. This article aims to provide a multidimensional analysis of the pathophysiological, clinical, ethical and legal considerations of nutritional support in the final stages of life. Methods: We conducted a narrative review of the literature published between January 2000 and June 2025 by searching the PubMed/MEDLINE, Web of Science, and Scopus databases and included original articles, clinical trials, reviews, international guidelines, and public policy documents involving adult population at the end of life. The narrative approach enabled the multidimensional integration of the collected data. Results: Terminally ill patients often develop anorexia and cachexia leading to irreversible muscle loss and resistance to nutritional support. CANH (enteral or parenteral) has limited success and carries increased risks. In advanced cancer and dementia, studies do not show clear benefits for survival or quality of life. Nutritional counseling and oral supplements may help alleviate symptoms, but manual feeding remains the standard of care in the terminal stages. In ICU settings, starting or maintaining CANH demands careful evaluation of goals, prognosis, and burdens. Cultural legal differences and approaches between countries also influence clinical practice and family expectations. Conclusions: CANH at the end of life should be viewed as a medical intervention that requires both scientific and ethical justification. The decision to initiate or discontinue it should be individualized. Clear and empathetic communication between the medical team, patient, and family is essential to avoid inappropriate decisions. Full article

Background: Human adenovirus type 4 (HAdV-4), the sole member of species Human mastadenovirus E (HAdV-E), is of zoonotic origin and has established stable human transmission through recombination, conferring distinctive host adaptation and pathogenicity. It causes respiratory and ocular diseases, with a significant risk of severe pneumonia in children. No targeted antivirals are approved for routine use, leaving supportive care as the primary management. China bears a relatively high HAdV-4 disease burden in Asia. Methods: To generate neutralizing nanobodies (Nbs) against HAdV-4, we employed an alpaca immunization strategy using hexon protein from Ad4-RI67 strain, followed by the isolation of hexon-specific nanobodies. The epitope competition and molecular docking was employed to analysis the binding site of the Nbs’. We engineered VHH-Fc fusions by conjugating VHH domains to human IgG1 Fc. The lead candidate, NVA17, showed efficacy in both in vitro and in vivo (Stat1^+/− mouse model). Flow cytometric analysis was employed to assess the downstream immune effects of NVA17 in vivo. Its intracellular neutralization mechanism was further investigated through confocal microscopy by examining co-localization in TRIM21-overexpressing and knockdown cells. Results: The isolated nanobodies revealed epitopes distinct from those targeted by known antibodies. The lead candidate NVA17 demonstrated potent neutralizing activity in vitro (IC₅₀ < 10 ng/mL). In the Stat1^+/− mouse model, NVA17 provided complete protection against lethal challenge, significantly reduced viral load in the lungs, and ameliorated pathological damage. NVA17 treatment dose-dependently reversed the virus-induced reduction in immune cell counts and enhanced cytotoxicity, suggesting a systemic immunomodulatory effect. Mechanistic studies indicated that the antiviral activity of NVA17 partly depends on the TRIM21-mediated antibody-dependent intracellular neutralization (ADIN) pathway, whereby TRIM21 terminates the viral life cycle by promoting viral degradation via K48-linked ubiquitination. Conclusions: We have identified multiple antibody candidates, particularly NVA17, with significant therapeutic potential for developing antibody-based treatments against HAdV-4. This offers a targeted intervention strategy to counter the current lack of specific antiviral therapies. Full article

The growing interest in high-voltage direct current (HVDC) technology and multi-terminal HVDCs (MTDCs) has motivated the evaluation of DC circuit breakers (DCCBs) for increased operational flexibility. While modeling DCCBs remains essential, their complex structures and modeling techniques require careful consideration. In this context, trade-offs in modeling accuracy and complexity of DCCBs are of paramount importance, and hence, benchmarking-based modeling methodology for hybrid and non-hybrid DCCBs is performed in this study. To this end, the performance of different aggregated DCCB technologies, namely hybrid DCCBs, simple DCCBs, and voltage-source DCCBs, is benchmarked for MTDC applications, with the full representation of hybrid DCCBs taken as the baseline for comparison. First, it is shown that the aggregated hybrid DCCB provides an accurate representation of the full hybrid DCCB’s performance. This is followed by an analysis of the parameters for the simple DCCB and voltage-source DCCB (VSCB) that enable their performance to closely match that of the aggregated hybrid DCCB. Finally, the impact of aggregated DCCB models on voltage transients within a test system is analyzed, demonstrating the effectiveness of aggregated modeling across different DCCB technologies. Simulation-based analyses are conducted in PSCAD/EMTDC to compare the performance of different aggregated DCCB models. Full article

Background/Objectives: An increasing number of older individuals require general anaesthesia for major non-cardiac surgery, with 20% displaying postoperative complications. Regional cerebral oxygen saturation (rSO₂) correlates with the gold standard of mixed venous oxygen saturation, indicating global perfusion. We hypothesised that rSO₂-based anaesthesia reduces organ dysfunction and morbidity after major non-cardiac surgery. Methods: In Singapore and Toronto, we conducted a prospective, double-blind, randomised controlled trial in elderly patients undergoing major non-cardiac surgery, after obtaining research ethics board permission and informed consent. This RCT followed the CONSORT guidelines. Patients received bilateral cerebral oximetry sensors, and the control group received standard care. In the intervention group, an algorithm restored rSO₂ if it dropped 10% below baseline for >15 s by adjusting cerebral perfusion pressure, inspired oxygen concentration, end-tidal carbon dioxide, depth of anaesthesia, haemoglobin, and cardiac index. Postoperative complications and outcomes were noted. Categorical data were analysed using Chi-square or Fisher’s exact tests and continuous data using a t-test or a Mann–Whitney U test. The study was powered for 394 patients, but due to the COVID-19 pandemic and funding constraints, this study was terminated at 101 patients. Results: Of 101 patients, 49 were randomised to the control and 52 to the intervention group. A total of 31 (63%) patients in the control group and 30 (58%) in the interventional exhibited bilateral cerebral desaturation. Time of cumulative cerebral desaturation was longer in the control group (23 ± 48 min vs. 9 ± 15 min, respectively, p = 0.01). A total of 142 algorithm-based treatments were employed, restoring rSO₂ in 29 (86%) patients. Both groups displayed equal postoperative outcomes. Conclusions: In major non-cardiac surgery, cerebral desaturation is prevalent in over 85% of patients. Although algorithm-guided therapy restored rSO₂ in the majority of patients, it did not result in reduced postoperative morbidity. Full article