Objective To evaluate short- and long-term outcomes after modified Stage I palliation for hypoplastic left heart syndrome. Methods This retrospective single-center study analyzed 128 patients with hypoplastic left heart syndrome treated between 1993 and 2023. Patients were divided into 2 groups: Era I (n = 36), from 1993 to 2001, included patients who underwent the classic Norwood procedure, and Era II (n = 92), from 2002 to 2023, included patients who underwent modified Stage I palliation. Postoperative outcomes, including the need for postoperative extracorporeal membrane oxygenation, peritoneal dialysis, recoarctation rate, and overall survival, were compared between eras. Results Median follow-up was 9.7 years, with 100% completeness for survival data, and ranged from 0.9 to 30.9 years. Ninety-day survival improved from 69.4% in Era I to 95.7% in Era II (P < .001). Transplant-free survival improved from 47% to 84% at 5 years (P < .001) and from 42% to 71% at 20 years (P < .001). Only 1 patient in Era II required postoperative extracorporeal membrane oxygenation. The use of peritoneal dialysis decreased from 86.1% to 22.8%, and recoarctation rate decreased from 13.9% to 7.6%. Conclusions On the foundation of important developments in perioperative care across the study period, the introduction of modified Stage I palliation may have contributed to improved survival and reduced postoperative morbidity, and may represent an alternative to centralization of care.

Background: Culturally and Racially Marginalised (CaRM) communities in Australia encounter subtle and covert forms of prejudice, commonly referred to as “new racism”. Within healthcare settings, these experiences can shape trust, engagement, and patterns of help-seeking. Mental health nurses are often the first point of contact in care delivery, and their ability to recognise, respond to, and mitigate the impacts of new racism is critical for fostering therapeutic relationships and supporting equitable access. Understanding how CaRM communities perceive the conditions that influence their mental health service use is fundamental for informing more equitable and culturally responsive care. Objective: This study explored the viewpoints of CaRM community members regarding the factors they consider important for addressing new racism in healthcare systems and supporting engagement with mental health services. Design: Q methodology was used to identify statistically derived viewpoints that reflect shared viewpoints about the conditions perceived as critical for addressing the impacts of new racism on mental health service use. Setting: Participants were recruited from culturally and linguistically diverse communities across Australia through community settings, social media, and professional networks. Participants: Thirty-five individuals from CaRM backgrounds completed the Q-sort. Methods: This Q methodology consisted of five steps: (1) set up of the Q-sorting instrument, (2) selection of participants, (3) data collection, (4) factor analysis, and (5) factor interpretation. Results: Three distinct viewpoints were identified: (1) raising awareness of mental health issues within CaRM communities (community-focused), (2) providing visible anti-racism and culturally safe services (service-focused), and (3) recognising and formally addressing new racism within healthcare systems (policy-focused). Conclusions: This study offers the first empirically derived, community-informed set of viewpoints on addressing new racism in Australian mental healthcare. While exploratory, the findings highlight multi-level considerations that are potentially relevant to mental health nursing practice, and may be useful to inform future research, policy development, and service redesign aimed at strengthening cultural responsiveness and equity in mental health systems.

Abstract Introduction Rheumatic connective tissue diseases (RCTDs) are chronic systemic autoimmune disorders frequently complicated by cardiovascular involvement, which represents a major cause of morbidity and mortality. Subclinical cardiac manifestations may remain unrecognized and may be associated with systemic inflammation and laboratory abnormalities. Objective To evaluate the prevalence and characteristics of cardiac manifestations in patients with RCTDs and to assess their association with serological status and selected hematological and biochemical parameters. Methods This observational study included 110 adult patients hospitalized and treated for rheumatic connective tissue diseases over a one-year period. Patients were classified into seropositive and seronegative groups based on autoantibody profiles. All participants underwent clinical evaluation, electrocardiography, and transthoracic echocardiography. Hematological, inflammatory, biochemical, electrolyte, enzyme, and serum protein parameters were analyzed. Results Cardiac involvement was more frequently observed in seropositive patients and increased significantly with age. Ventricular hypertrophy and atrioventricular or intraventricular conduction disturbances were the most common abnormalities in this group. Seropositive patients showed significantly lower hematocrit, hemoglobin, calcium, and albumin levels, as well as higher erythrocyte sedimentation rate, fibrinogen, triglycerides, lactate dehydrogenase, and serum urea levels. In the seropositive group, demonstrated significant negative correlations with hematocrit, hemoglobin, albumin, and calcium. Conclusion Seropositive rheumatic connective tissue diseases are associated with a higher prevalence of subclinical cardiac involvement and distinct laboratory abnormalities reflecting chronic inflammation and myocardial remodeling. Integrated cardiovascular assessment combined with laboratory evaluation may facilitate early detection of cardiac involvement in this patient population.

In patients with heart failure with reduced ejection fraction (HFrEF), the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has consistently demonstrated a beneficial therapeutic effect, vastly in non-Chagas trials. Less is known about the efficacy and safety of sacubitril-valsartan compared with standard of care in patients with Chagas cardiomyopathy, a common but often neglected etiology of nonischemic HFrEF. We aimed to perform a systematic review and meta-analysis to investigate whether sacubitril-valsartan is superior to enalapril in patients with heart failure (HF) due to Chagas cardiomyopathy. PubMed, Embase and Cochrane database were searched for randomized controlled trials (RCTs) that compared sacubitril-valsartan with enalapril in patients with HF due to Chagas cardiomyopathy. Efficacy outcomes were (1) cardiovascular (CV) death; (2) HF hospitalization; (3) relative change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline; and safety outcomes were (4) serious adverse events (SAEs); and (5) drug discontinuation due to adverse events (AEs). Cochrane's Review Manager Version 7.2.0 (RevMan, 2024) was used for all statistical analyses. Heterogeneity was examined with I² statistics. Hazard ratios (HR), risk ratios (RR), and mean differences (MD) with 95% confidence intervals (CIs) were pooled using an inverse-variance random-effects model. Three RCTs comprising 1,112 patients were included, of whom 463 (38%) were females. A total of 615 (50.02%) patients received sacubitril–valsartan, while 610 (49.8%) were treated with enalapril. The mean age was 63.67±10.6 years, and the mean left ventricular ejection fraction (LVEF) was 29.8%±7.2%. There was no statistically significant difference in CV death (HR 0.92; 95% CI 0.72 to 1.18; p=0.51; I²=0; Figure 1A) and HF hospitalization (HR 0.93; 95% CI 0.72 to 1.20; p=0.59; I²=0; Figure 1B) between sacubitril-valsartan and enalapril groups. However, there was a statistically significant reduction in NT-proBNP favoring enalapril over sacubitril-valsartan (MD 0.68; 95% CI 0.63 to 0.73; p<0.00001; I²=0; Figure 1C). No statistically significant difference in SAEs was found between the two treatment arms (RR 0.90; 95% CI 0.79 to 1.03; p=0.12; I²=0; Figure 2A), but there was a trend towards fewer drug discontinuations due to AEs with sacubitril–valsartan compared with enalapril (RR 0.51; 95% CI 0.26 to 1.01; p=0.05; I²=32% Figure 2B). In this meta-analysis of 1,112 patients with HF due to Chagas cardiomyopathy, sacubitril-valsartan did not statistically significantly reduce CV death or HF hospitalization, relative to enalapril. There was a significant difference between groups in terms of NT-proBNP reduction favoring enalapril. Moreover, sacubitril-valsartan was not superior to enalapril with respect to safety outcomes.Figure 1.Efficacy outcomes.For image description, please refer to the figure legend and surrounding text.Figure 2.Safety outcomes.For image description, please refer to the figure legend and surrounding text.

Inclisiran effectively reduces low-density lipoprotein cholesterol (LDL-C) by suppressing proprotein convertase subtilisin/kexin type 9 (PSCK9) in patients on maximally tolerated statins with atherosclerotic cardiovascular disease (ASCVD) or risk equivalent. However, less is known about the efficacy of inclisiran as a monotherapy strategy for LDL-C reduction in patients with elevated levels but who are not on statins, ezetimibe, or any other lipid-lowering therapy (LLT). To investigate whether the lipid-lowering efficacy of inclisiran in LDL-C reduction indicates a significant pharmacodynamic effect regardless of baseline cardiovascular risk in patients with hypercholesterolemia without any LLT. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing inclisiran sodium at dose of 300 mg (equivalent to 284 mg inclisiran) with placebo in adults with hypercholesterolemia who were not on statin, ezetimibe, nor any other LLT at baseline for evaluating the lipid-lowering efficacy of inclisiran as monotherapy. Outcomes of interest were (1) primary efficacy endpoint as percentage change in LDL-C from baseline, in patients without any background LLT and in those without statin use, and (2) percentage change in PCSK9 levels from baseline. R software version 4.3.1 was used for statistical analysis to estimate pooled effects of mean difference (MD) and 95% confidence intervals (CI) under e random-effects model. Heterogeneity was examined with I² statistics. We included five RCTs comprising 540 patients, of whom 311 (58%) were treated with inclisiran monotherapy, and the remaining 229 (42%) received placebo. Median follow-up ranged from 6 to 18 months (or 183 to 540 days). When compared with placebo, patients treated with inclisiran monotherapy who were not on any LLT had a significant decrease in percentage change in LDL-C from baseline (MD −46.24%; 95% CI −51.35 to −41.12; p<0.01; Figure 1A), with no significant difference when stratified by low risk versus high-risk population (test for subgroup difference p=0.33; Figure 1A). Similarly, inclisiran monotherapy lowered the LDL-C from baseline in patients without statin at baseline by about 53% more compared with placebo (MD −52.57%; 95% CI −62.34 to −42.80; p<0.01; Figure 1B). Moreover, the inclisiran group showed a significant 77% reduction in PCSK9 levels compared with the placebo group (MD −77.29%; 95% CI −84.31 to −70.27; p<0.01; Figure 2A). In this meta-analysis of RCTs evaluating patients with hypercholesterolemia without any background LLTs, inclisiran monotherapy significantly reduced percentage change in LDL-C from baseline, regardless of ASCVD risk. These findings were consistent in a sensitivity analysis only in patients without statin use at baseline, as well as in reduction of PSCK9 levels.Inclisiran Figure 1For image description, please refer to the figure legend and surrounding text.  Inclisiran Figure 2For image description, please refer to the figure legend and surrounding text.

Oral anticoagulation (OAC) and antiplatelet therapy (APT) represent a well-established preventative strategy against stroke, stent-related, and coronary ischemic events in patients with atrial fibrillation (AF) and coronary artery disease (CAD) following percutaneous coronary intervention (PCI). Less is known about the efficacy and safety of OAC as monotherapy compared with combined antithrombotic therapy in the subgroup of patients with drug-eluting stent (DES) implantation. To investigate whether deescalating from combination therapy of OAC with single APT to OAC monotherapy provides similar protection from major ischemic and bleeding endpoints in patients with AF and stable CAD following DES implantation. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) that compared OAC monotherapy (vitamin K antagonist or direct oral anticoagulant) with combination antithrombotic therapy of OAC plus single APT in patients with AF and CAD who underwent PCI with DES and reported the efficacy and safety composite outcomes of mortality, ischemia (myocardial infarction, stroke, or systemic embolism), and major bleeding or clinically relevant bleeding (CRNB). Cochrane's Review Manager Version 7.12.0 (RevMan, 2024) was used for statistical analysis to estimate pooled effects of hazard ratio (HR) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was examined with I² statistics. We included four RCTs comprising a total of 2570 patients, of whom 1302 (51%) were treated with OAC monotherapy, and the remaining 1268 (49%) were treated with combination therapy of OAC+APT. Median follow-up ranged from 12 to 30 months. There was no statistically significant difference in the efficacy endpoints of major ischemic composite (HR 0.94; 95% CI 0.65 to 1.36; p=0.75; Figure 1A) and the net clinical composite (HR 0.77; 95% CI 0.37 to 1.60; p=0.49; Figure 1B) between OAC monotherapy and OAC+APT combination therapy. However, there was a statistically significant reduction in the safety endpoint composite of major bleeding or CRNB with OAC monotherapy (HR 0.47; 95% CI 0.30 to 0.75; p=0.001; Figure 2A) compared with OAC+APT combination therapy, which was consistent in a sensitivity analysis of patients treated with predominantly new-generation DES (HR 0.38; 95% CI 0.25 to 0.59; p<0.0001; Figure 2B). Among patients with AF and prior PCI with DES implantation, OAC monotherapy statistically significantly reduced major bleeding or CRNB endpoint by 52% compared with combined antithrombotic therapy, but there was no significant difference between groups in terms of major ischemia or net clinical benefit.OAC Figure 1For image description, please refer to the figure legend and surrounding text.  OAC Figure 2For image description, please refer to the figure legend and surrounding text.

Commercially available graphene quantum dots (GQDs) are promising nanomaterials for applications in research and preclinical diagnostics, drug delivery, and bioimaging. Their bioactivity is highly dependent on dose, route of exposure, duration, cell type, uptake mechanisms, tissue and cellular distribution, and physicochemical properties. This study aimed to evaluate genotoxic, cytotoxic, and cytostatic endpoints of blue- (B-GQDs) and green-emitting (G-GQDs) GQDs in human blood and salivary leukocytes. GQDs were tested at concentrations ranging from 2.5 to 100 µg/mL using distinct treatment periods. Fourier transform infrared spectroscopy (FTIR), trypan blue exclusion, comet, and cytokinesis-block micronucleus cytome (CBMN cyt) assays were performed. FTIR analysis revealed that G-GQDs, unlike B-GQDs, exhibit an absorption band typically associated with amine functional groups, which may contribute to their pronounced genotoxic effects. Peripheral blood mononuclear cells and salivary leukocytes showed higher sensitivity to G-GQDs compared to whole blood samples. Although no cytotoxic effects were observed, both GQDs induced significant DNA damage, with G-GQDs demonstrating greater genotoxic potential. These findings demonstrate that GQDs can induce DNA damage in the absence of detectable cytotoxic effects under the conditions tested, highlighting the importance of considering both physicochemical properties and cellular models in the safety assessment of nanomaterials.

Evidence suggests psychological factors including personality traits can have impact on the development and course of irritable bowel syndrome (IBS) and associated health‐related quality of life (HrQoL), with large individual heterogeneity. Main aim of this study was to examine between‐persons associations and within‐sample concurrent associations of the personality traits neuroticism, extraversion, conscientiousness, openness and agreeableness with gastrointestinal (GI) symptoms, psychological factors and HrQoL in IBS‐patients.

SARS‐CoV‐2 infection is driven by extensive interactions between viral proteins and host cellular factors, yet the structural properties of host proteins within these interaction networks remain incompletely understood. Intrinsically disordered proteins and regions are key contributors to protein–protein interaction networks due to their conformational flexibility and associated with it multifunctionality, binding promiscuity, and regulatory versatility. In this study, we performed a systematic, proteome‐wide analysis of intrinsic disorder in human proteins interacting with SARS‐CoV‐2 by integrating five experimentally validated interaction datasets comprising 2055 unique host proteins. Using disorder prediction, structural confidence assessment, functional and domain annotation, protein–protein interaction network analysis, phase‐separation propensity estimation, and independent validation with the D2P2 platform on a selected set of proteins, we characterized the structural organization of the SARS‐CoV‐2 human interactome. Our results reveal a balanced distribution of ordered and disordered host proteins, distinct functional and domain signatures across disorder classes, consistent inverse relationships between disorder and structural confidence, and increased network connectivity and phase‐separation propensity among highly disordered interactors. These findings indicate that SARS‐CoV‐2 exploits structural diversity within the host proteome rather than preferentially targeting a single disorder class and highlight intrinsic disorder as a key contributor to interaction plasticity and network organization at the systems level.

This case report presents an updated interpretation of genetic and chronological data from human remains discovered in Bezdanjača Cave, a Bronze Age burial site located in the Lika region of Croatia. The cave contains a complex necropolis with at least 57 graves and up to 200 individuals, which indicates its use as a collective burial site during the Middle and Late Bronze Age. Based on ancient DNA analysis, 13 males were identified among 38 analyzed individuals, with the majority belonging to the Y-chromosome haplogroup R1b, commonly associated with Bronze Age populations. However, two individuals were assigned to haplogroup I2a1a (I-Y3120). The I2a lineage has deep roots in Europe, and its presence has been confirmed in prehistoric contexts in Croatia and the region. However, newly obtained radiocarbon dates from occipital bones reveal that at least one of the two I2a1a individuals from Bezdanjača Cave dates to the Early Modern period (1645-1950 calibrated CE), which indicates that the remains were deposited in the cave much later than previously assumed. At the same time, these new data do not contradict the possible presence of the I2a1a lineage in Bronze Age populations in this area, as Bronze Age I2a1a samples have been reported from other archaeological sites in Croatia and the wider region. These findings, presented here for the first time, highlight the risks of assuming chronological homogeneity based solely on archaeological context and demonstrate the necessity of direct radiocarbon dating when integrating archaeological and genetic data. An interdisciplinary approach and careful chronological verification in ancient DNA research are essential to avoid misinterpretations in broader population genetic studies.

Aim To investigate integrated biochemical and glycomic signatures in humans related to coordinated metabolic and endocrine adaptations during prolonged fasting, which are essential for maintaining systemic homeostasis. Methods This single-arm longitudinal interventional study enrolled five healthy adults who underwent a 72-hour water-only fast. Blood samples were collected at baseline (T0), immediately after fasting (T1), and after 11 days of refeeding (T2). A broad panel of biochemical, hormonal, inflammatory, and glycomic parameters was determined. Time-dependent differences were evaluated using the Friedman test. Results Fasting induced a distinct biphasic response across multiple circulating markers, with significant alterations in total cholesterol, C-reactive protein, thyroid-stimulating hormone, and free triiodothyronine at T1 followed by recovery toward baseline at T2. Insulin and glucose concentrations declined during fasting and increased after refeeding, although these changes did not reach statistical significance. Plasma, immunoglobulin G (IgG), and IgA N-glycosylation profiles were extensively remodeled, which indicated dynamic metabolic and immune system adaptation. Liver enzymes, electrolytes, and most lipid fractions exhibited only minor and reversible fluctuations. Conclusion A 72-hour fast was associated with metabolic and hormonal changes consistent with an environment conducive to autophagy, although autophagy was not measured directly. The protocol appeared feasible and well tolerated in a small cohort of healthy adults. Given the limited sample size, these findings should be considered preliminary and require confirmation in larger studies incorporating direct autophagy markers and additional time points.

In the realm of preventive medicine, reinforcement of a zero-tolerance stance on cigarette smoking is imperative. The use of heat-not-burn (HnB) technology by individuals who are unable to quit smoking has prompted strong discussions in both the public health and clinical domains. This raises the question of whether exposure to cigarettes or HnB products has a different effect on blood pressure (BP) values and whether this effect depends on the concentration of heavy metals. A total of 33 participants were divided into four exposure groups: passive HnB exposure (n=7), active HnB users (n=4), passive cigarette smokers (n=11), and active cigarette smokers (n=9). Blood concentrations of cadmium (Cd) and lead (Pb) were determined by atomic absorption spectroscopy (AAS) using a Graphite Furnace Atomic Absorption Spectrometer, Agilent 240Z AA (Agilent Technologies, Santa Clara, CA, USA). Samples were prepared by wet digestion with nitric acid solution. After centrifugation, the supernatant was transferred into vials for AAS analysis. Concentrations of Cd and Pb were measured before and after exposure, and changes were analyzed using generalized linear models (GLM) adjusted for sex, age, and body mass index (BMI). All participants were smokers who had stopped smoking five days prior to the experiment. None of the participants had any chronic diseases. After a five-day abstinence (washout period), they were exposed to active and passive consumption of HnB or traditional cigarettes. BP was measured before and after exposure to tobacco smoke. Average Cd levels were similar across all groups (p = 0.55): passive HnB 1.59 µg/L, active HnB 1.29 µg/L, passive cigarette smokers 1.65 µg/L, and active cigarette smokers 1.64 µg/L. Pb levels varied significantly by exposure type (p = 0.006), as follows: 35.95 µg/L with passive HnB exposure, 26.98 µg/L with active HnB exposure, 52.45 µg/L and 36.50 µg/L in passive and active cigarette smokers, respectively. Upon monitoring, an elevation in Cd levels was significantly associated with a rise in systolic pressure (p = 0.026) and a decrease in diastolic pressure (p = 0.006), indicating an increase in pulse pressure and potential arterial stiffness. Pb concentration showed no direct effect on hemodynamic parameters. These findings suggest that Cd and Pb levels vary based on type of exposure. There was a significant difference between traditional cigarettes and HNB products, with the latter exhibiting lower concentrations, as well as between active and passive exposure. Changes in BP tend to be more closely linked to Cd, as higher levels correlate with increased systolic and decreased diastolic pressures, indicating its role in arterial stiffness and early vascular dysfunction.

Atherosclerosis is a progressive vascular disease characterized by lipid-rich plaque accumulation, oxidative stress, and chronic inflammation, contributing to coronary heart disease, stroke, and peripheral arterial disease. This study investigated the impact of inflammation, vascular calcification, and statin therapy on redox balance in blood and carotid artery plaques, aiming to identify potential biomarkers for disease assessment. Thirty-two patients undergoing carotid endarterectomy provided 34 plaque samples. Enzyme activities in plaque/erythrocytes and –SH group concentration in plasma/plaque were measured. Pathological analysis was performed to determine inflammation/calcification grade, the presence of mast cells and plaque composition. The results showed that mast cells were associated with reduced non-protein –SH groups, indicating selective thiol consumption and serving as a qualitative marker of oxidative burden. Reduced catalase activity in erythrocytes was associated with advanced calcification, pointing to long-standing systemic oxidative stress. Statin therapy enhanced systemic superoxide-dismutase 1 activity, increased –SH groups, and modulated plaque-specific glutathione reductase activity, attenuating sex-related differences in redox regulation. These findings highlight the complex interplay between systemic and local oxidative processes in atherosclerosis through alterations in redox-related biomarkers such as plasma –SH group concentrations and catalase activity.