Search Results (707)

Background: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) were historically considered contraindicated in severe aortic stenosis (AS) due to theoretical haemodynamic risks. Contemporary evidence increasingly challenges this paradigm, yet data on preoperative use and postoperative outcomes remain limited. We examined the association between preoperative ACEi/ARB use and mortality following aortic valve replacement. Methods: We conducted a retrospective cohort study of 198 consecutive patients undergoing transcatheter (TAVI) or surgical aortic valve replacement (SAVR) at a single tertiary centre between May 2020 and March 2025. Complete one-year follow up was available for 185 patients (93%). The primary outcome was one-year all-cause mortality. Multivariable logistic regression adjusted for age, sex, hypertension, diabetes, LVEF, and procedure type. Results: Of 198 patients, 80 (40%) were receiving ACEi/ARB therapy preoperatively. ACEi/ARB users had a higher prevalence of hypertension (82% vs. 53%, p < 0.001) and diabetes (48% vs. 27%, p = 0.005) but similar age, valve area, and ejection fraction. Unadjusted one-year mortality was lower in the ACEi/ARB group (7% vs. 19%; odds ratio [OR] 0.33, 95% CI 0.12–0.91, p = 0.030). After multivariable adjustment for confounders including age, diabetes, and hypertension, the association did not reach statistical significance (adjusted OR 0.33, 95% CI 0.10–1.12, p = 0.075). Among diabetic patients, unadjusted one-year mortality was numerically lower in the ACEi/ARB group (12% vs. 35%, p = 0.038); however, six subgroup comparisons were performed and this result would not survive Bonferroni correction (threshold p < 0.008). This exploratory finding should be interpreted with caution given the small sample size and absence of adjustment for confounders. Conclusions: Preoperative ACEi/ARB use was associated with lower unadjusted one-year mortality, but this association did not reach statistical significance after multivariable adjustment and residual confounding cannot be excluded. ACEi/ARB use was not associated with increased mortality in this cohort. These hypothesis-generating findings from a single-centre observational study require confirmation in adequately powered prospective trials. Full article

Atherosclerosis remains the leading cause of death worldwide and imposes a major healthcare burden. Physiologically, elimination of cholesterol from the arterial wall depends on reverse cholesterol transport (RCT). RCT requires access to HDL and apolipoprotein A-I (ApoA-I) to lesional macrophages/foam cells. The endothelial glycocalyx is a dynamic and injury-sensitive layer of proteoglycans and glycosaminoglycans (including hyaluronan). It contributes to vascular barrier properties, leukocyte adhesion, mechanotransduction, and macromolecular transport. In atherosclerosis, glycocalyx structure and function are altered; this may facilitate entry/retention of atherogenic lipoproteins and may also alter transport conditions relevant to cholesterol efflux pathways. This article presents a mechanistic hypothesis: short, transient, systemic hyaluronidase exposure could temporarily remodel glycocalyx/extracellular matrix components and thereby facilitate conditions permissive for regulated transport processes relevant to RCT. However, the proposed link between glycocalyx remodeling and improved lesional cholesterol efflux remains theoretical. Direct in vivo evidence that the endothelial glycocalyx is a dominant barrier limiting HDL- or ApoA-I-mediated cholesterol efflux from plaque macrophages is currently limited. Moreover, glycocalyx degradation is widely associated with endothelial dysfunction, increased permeability, inflammation, and thrombosis, all of which could aggravate rather than ameliorate atherosclerosis. Human pharmacokinetic data indicate a very short plasma half-life of circulating hyaluronidase activity, suggesting that any systemic enzymatic effect is brief. Nevertheless, the biological consequences of repeated degradation–regeneration cycles, especially in high-risk states such as diabetes, inflammation, oxidative stress, or chronic kidney disease, remain incompletely understood. Evidence supporting clinical benefit in atherosclerosis is currently limited to heterogeneous animal experiments, historical uncontrolled reports, and a small number of anecdotal case observations, whereas randomized trials have only been performed in other settings such as acute myocardial infarction and do not establish efficacy for plaque regression. We therefore provide a balanced evaluation of knowns, uncertainties, alternative interpretations, potential risks, dosing unknowns, and a translational research agenda including mechanistic preclinical studies, biomarker development, imaging, and carefully designed early-phase clinical investigation. Full article

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder associated with adverse maternal and fetal outcomes. However, current diagnostic strategies have a limited capacity to identify women at risk early in pregnancy. In this longitudinal prospective pilot study, 200 pregnant Mexican women were recruited at 11–14 weeks and underwent follow-up throughout pregnancy. Of these, 34 women (19 with GDM and 15 with normal glucose tolerance [NGT]) completed follow-up and were included in the final analyses. Most withdrawals were due to logistical constraints, although the reduced final sample size should be considered when interpreting generalizability. Nine serum proteins (ADIPOQ, AFM, FABP4, IGFBP-5, PAPP-A, PAPP-A2, RBP4, RETN, SHBG) were measured simultaneously using an antibody array and subsequently validated by ELISA. FABP4 showed the greatest increase in the first trimester (4.9-fold, p = 0.0105) and the highest apparent discriminative performance (AUC = 0.91), which declined in the second and third trimesters. Exploratory, hypothesis-generating multivariable analyses suggested a stronger association when FABP4 was combined with gravidity and serum triglycerides (AUC up to 0.97). Overall, FABP4 emerged as a promising candidate biomarker for early GDM detection in Mexican women; however, these findings are preliminary and require validation in larger, independent cohorts to support early risk stratification. Full article

This study examines whether international food price dynamics provide a reliable signal of undernourishment and human development outcomes relevant to the attainment of SDG 2 (Zero Hunger) by 2030. We apply wavelet coherence analysis to the FAO Food Price Index and the prevalence of undernourishment (SDG Indicator 2.1.1) over 2001–2023, testing statistical significance against an AR(1) red-noise null hypothesis. Hybrid ARIMA–Random Forest models generate probabilistic price forecasts through 2030. Despite strong raw coherence (R² ≈ 0.77), only 7.8% of time–frequency cells achieve statistical significance, indicating that apparent co-movement largely reflects autocorrelation rather than substantive dependence. Where significant coherence emerges, it concentrates at medium-run horizons (3–6 years), consistent with undernourishment as a habitual dietary adequacy measure linked to sustained affordability pressures affecting health, productivity, and human capital formation. Rolling correlation analysis reveals suggestive evidence of a regime change around 2012—from negative to positive correlation—coinciding with a slowdown in progress toward reducing hunger, although the 5-year rolling windows yield only 19 observations, limiting the power of formal structural break tests. Price forecasts exhibit rapidly widening confidence intervals (by ±131 index points by 2030), underscoring fundamental limits to predictability. The annual PoU series comprises only 23 observations, which constrains the estimation of long-run (8–12-year) wavelet cycles; results at those horizons should therefore be interpreted with caution. These findings caution against mechanistic inferences from global price indices to hunger and human development outcomes, redirecting policy emphasis toward domestic transmission channels and nutrition-sensitive safety nets. Full article

Background: Ankle foot orthosis–footwear combination (AFO–FC) tuning involves structured adjustment of the AFO relative to footwear to optimise shank alignment and ground reaction force (GRF) positioning during stance. Although established biomechanical frameworks and clinical algorithms are available, variability in clinical implementation persists. Previous investigations have primarily relied on self-reported practice within single healthcare settings and have not, to our knowledge, systematically examined how orthotists articulate and apply tuning principles within structured clinical reasoning across diverse educational and practice environments. Objectives: This study aimed to determine the level of awareness and framework-based proficiency in AFO–FC tuning among practising orthotists in a geographically diverse convenience sample, to examine the extent to which AFO–FC tuning is integrated into routine clinical practice, and to explore associations between framework-based proficiency level and selected professional characteristics. Methods: A cross-sectional study was conducted using an online survey of practising orthotists (n = 245). Awareness of AFO–FC tuning and self-reported routine implementation were assessed. Framework-based proficiency was evaluated among respondents reporting awareness (n = 212) using structured content analysis of open-text responses within a predefined exploratory five-domain biomechanical framework, and classified as limited (0–1 domains), partial (2–3 domains), or full (4–5 domains). Associations between framework-based proficiency level and professional characteristics were examined using chi-square tests. Binary logistic regression was performed to assess the association between framework-based proficiency level and self-reported routine implementation. Results: Self-reported awareness of AFO–FC tuning was high (86.5%), whereas 53.5% reported routine implementation. Based on the framework scoring, 59.0% demonstrated limited framework-based proficiency, 31.6% partial framework-based proficiency, and 9.4% full framework-based proficiency. No statistically significant associations were observed in this sample between framework-based proficiency level and educational qualification, years of clinical experience, or annual AFO case volume (p > 0.05). Full framework-based proficiency was associated with higher odds of self-reported routine implementation (OR = 4.03, 95% CI 1.44–11.25, p = 0.008). Conclusions: Despite high self-reported awareness, framework-based proficiency in AFO–FC tuning was limited within this sample. Self-reported routine implementation was more frequently reported among respondents with higher framework-based proficiency, whereas no statistically significant associations were observed with educational level, clinical experience, or annual AFO case volume. These hypothesis-generating findings should be interpreted cautiously given the cross-sectional design and framework-based (non-validated) classification. Full article

The critical brain hypothesis proposes that neural systems operate near a phase transition to optimize information processing. A key method for investigating this hypothesis is the phenomenological renormalization group (pRG), which looks for scale-invariant features across levels of coarse-graining. One such feature is the power-law scaling of eigenvalues of covariance matrices of coarse-grained variables. However, the estimation of this scaling exponent, $\mu$, often relies on linear regression over arbitrarily selected ranges of the plot of eigenvalues versus rank. This heuristic “eyeballing” introduces uncontrolled bias and complicates the interpretation of observed scaling relationships. In order to obtain a more robust estimation of $\mu$, we do not fit the standard eigenvalue-vs-rank relationship, but rather the density of eigenvalues, for which standard protocols exist for fitting power laws to empirical data distributions. We demonstrate this approach using a synthetic model that replicates the scaling signatures of neural data while providing control over the system’s exponents as well as neural data obtained from publicly available Neuropixels recordings. We also establish standards for the minimal data required to quantify power-law behavior in a pRG eigenvalue analysis. Our approach contributes a tool for understanding the fundamental limitations imposed by spatial and temporal constraints of experimental datasets, which is required to rigorously assess the neural criticality hypothesis. Full article

Postural sway derived from center-of-pressure (CoP) trajectories is widely used to assess balance and fall risk in older adults, but conventional linear metrics mainly quantify sway magnitude and may overlook temporal organization. Guided by the loss-of-complexity hypothesis, we re-examined associations between fall history and linear and non-linear CoP metrics in an open-access dataset. Quiet-standing trials under eyes-open and eyes-closed conditions were analyzed in adults ≥60 years (fallers n = 19; non-fallers n = 57). To reduce confounding, propensity score matching was performed using age, sex, body mass index, activities of daily living level, illness status, number of medications, disability status, and orthosis/prosthesis use. Linear and non-linear indices, including recurrence quantification analysis, detrended fluctuation analysis, fractal dimension, multiscale entropy, stabilogram diffusion analysis, and sway density measures, were examined. After matching, no CoP metric differed significantly between groups. However, SHAP-based exploratory analysis suggested that non-linear features related to temporal structure and multiscale organization contributed more prominently to model output than conventional magnitude-based metrics. Given the limited sample size, these findings should be interpreted as exploratory and hypothesis-generating. Full article

Median overall survival remains a central endpoint in oncology, but it can obscure a clinically meaningful long tail of patients with advanced solid tumors who survive well beyond the median. One biological context in which this pattern may be relevant is tumor microenvironment (TME) acidosis. Driven by aerobic glycolysis, hypoxia, impaired perfusion, and proton-export programs, acidic TME is increasingly implicated in invasion, therapeutic resistance, and immune suppression. This narrative review examines TME acidosis as the primary biological framework and considers long-tail survival as a clinical lens through which its implications may be interpreted. We summarize the biological basis and heterogeneity of acidic TME, review current approaches to clinical and translational assessment of tumor acidity, including acidoCEST magnetic resonance imaging (MRI) and positron emission tomography (PET)-based approaches, and discuss the potential and limitations of alkalization-oriented interventions such as buffering and diet-based strategies. Particular attention is given to the distinction between direct measurements of tumor acidity and clinically feasible but indirect markers such as urinary pH, which should not be interpreted as a direct surrogate for local tumor extracellular pH. From a science-based medicine perspective, long-tail survival is treated here as a hypothesis-generating clinical signal rather than proof of causality. Overall, alkalization-oriented interventions appear biologically plausible and clinically testable, but current clinical evidence remains limited and context-dependent. Future progress will require mechanistically informed biomarkers, careful safety evaluation, and trial designs capable of detecting delayed separation of survival curves and tail-oriented patterns of benefit. Full article

Background: Neonatal and infant aortic arch reconstruction remains a high-risk cardiovascular procedure requiring effective cerebral and myocardial protection. Variability in perfusion strategies may influence early hemodynamic stability and postoperative recovery. This study aimed to evaluate the early and short-term cardiovascular outcomes of a standardized beating-heart aortic arch reconstruction strategy incorporating simultaneous antegrade selective cerebral and continuous coronary perfusion. Methods: In this retrospective single-center cohort study, 31 consecutive neonates and infants undergoing aortic arch reconstruction between November 2022 and December 2025 were analyzed. A standardized surgical protocol was applied, consisting of extensive ductal tissue resection, interdigitating posterior end-to-end anastomosis, anterior autologous pericardial patch augmentation, and moderate hypothermic antegrade selective cerebral perfusion combined with continuous coronary perfusion via innominate artery cannulation. Early postoperative outcomes and short-term echocardiographic follow-up results were assessed. Results: The cohort included 31 patients, 22.6% of whom had complex associated cardiac anomalies requiring concomitant procedures. Median cardiopulmonary bypass and aortic cross-clamp times were 119 and 64 min, respectively. There was no in-hospital mortality. Major complications were infrequent, and median intensive care unit stay was 5 days. During a median follow-up of 6.8 months, one patient (3.2%) developed recoarctation requiring reintervention. No late mortality was observed. Conclusions: A fully standardized beating-heart aortic arch reconstruction strategy incorporating simultaneous cerebral and coronary perfusion demonstrated favorable early cardiovascular and short-term outcomes, even in anatomically complex cases. Preservation of continuous coronary perfusion may be associated with improved myocardial stability and early postoperative recovery; however, these findings should be interpreted as observational and hypothesis-generating given the absence of a control group. Larger multicenter studies with longer follow-up are warranted to confirm these findings. Full article

Background: Severe obesity is associated with chronic low-grade inflammation, dysglycemia, and higher periodontitis risk. Sleeve gastrectomy (SG) is now a dominant bariatric procedure and reliably improves weight and metabolic status yet reported oral and periodontal trajectories after surgery remain heterogeneous. Objective: To synthesize SG-centered evidence on periodontal outcomes, oral and gut microbiome remodeling, and mechanistic pathways that may link postoperative physiology to the gut–oral axis. Methods: We conducted a structured narrative review guided by SANRA principles using targeted searches of PubMed/MEDLINE, Web of Science, Scopus, and Embase, complemented by citation chaining of key reviews and mechanistic anchor papers; evidence was organized into clinical, oral microbiome, gut microbiome, and mechanistic gut–oral axis streams and interpreted with a pragmatic evidence hierarchy. Results: Small prospective SG cohorts suggest bleeding on probing (BOP), gingival indices, and sometimes probing depth (PD) may improve in some patients, particularly alongside weight loss, improved glycemic control, and lower systemic inflammatory burden, whereas clinical attachment level (CAL) and longer-term structural trajectories remain mixed; mixed-procedure syntheses also report early deterioration in some settings. Oral microbiome findings after bariatric surgery are site- and time-dependent, and salivary signals do not necessarily mirror subgingival plaque, whereas gut microbiome remodeling and bile acid signaling changes are more consistently reported and provide plausible but indirect mediator candidates. At the same time, reflux, vomiting, salivary changes, diet patterning, medications, and periodontal care can modify or counteract potential periodontal benefits and may increase competing risks such as caries or erosive tooth wear. Conclusions: The SG–gut–oral axis-periodontal pathway is a biologically plausible working hypothesis rather than a proven causal pathway in humans. The present evidence for any periodontal benefit relies mainly on small observational cohorts and is most credibly demonstrated for inflammatory, not structural, endpoints. Full article

Background/Objectives: Joubert syndrome (JS) is a rare neurodevelopmental disorder characterized by cerebellar and brainstem malformations, resulting in a complex and heterogeneous motor phenotype. Despite increasing clinical recognition, functional assessment and physiotherapy strategies in this population remain insufficiently characterized. This study aimed to synthesize current rehabilitation evidence and to propose a conceptual framework for functional motor assessment in children with JS. Methods: A structured narrative review was conducted across PubMed, Scopus, Web of Science, EBSCOhost, the Cochrane Library, and PEDro databases, including studies published between 2000 and 2026. Eligible studies involved pediatric patients (0–18 years) with JS and reported physiotherapy or motor-related outcomes. Data were synthesized descriptively, and recurring functional domains were identified to inform the development of a conceptual framework. Results: Ten studies (eight case reports and two case series) were included. Rehabilitation approaches were heterogeneous and predominantly multidisciplinary, focusing on postural control, trunk stability, and motor milestone acquisition. Functional improvements were reported across studies; however, outcome measures were primarily based on generic pediatric tools such as GMFM-88 and WeeFIM. These tools did not fully capture the multidimensional nature of motor impairment, particularly in relation to regulatory and sensorimotor domains. Evidence also suggested that postural control and gross motor performance may not fully correspond, highlighting additional functional components such as axial control and thoracoabdominal organization. Given the absence of formal risk-of-bias assessment and the low methodological quality of included studies, all findings should be interpreted as exploratory. Conclusions: Current functional assessment in JS may not adequately reflect the interaction between regulatory processes, sensorimotor integration, and motor control. The proposed conceptual framework provides a multidimensional, hypothesis-generating perspective that may support clinical reasoning and physiotherapy planning. Further research is required to validate this framework and to develop more sensitive, syndrome-specific assessment tools. Full article

Background and Objectives: Metacognition-related processes (e.g., confidence calibration, self-evaluation and the use of feedback) have been linked to cognitive insight, self-evaluation, and daily functioning in psychosis. However, clinic-based assessments only provide limited information. Digital methods may capture state-like variations and contextual factors, but it is unclear to what extent they operationalise core metacognitive monitoring constructs versus adjacent self-evaluative/insight-related constructs. We mapped digital approaches used to assess metacognition-related constructs across the psychosis spectrum, summarising the associated feasibility and validity. Materials and Methods: We conducted a scoping review (PRISMA-ScR) of psychosis-spectrum studies that used digital tools to assess metacognition-related targets. These included ecological momentary assessment/experience sampling (EMA/ESM), task-based paradigms with confidence ratings, and hybrid approaches. Searches covered MEDLINE (via PubMed), Scopus, and IEEE Xplore, with the final search run on 15 December 2025. We charted constructs, operationalisations, feasibility/engagement indices and reported links with clinical or functional measures. Results: The empirical evidence map comprised 13 studies directly assessing metacognition-related constructs; eight additional implementation/methodological sources were synthesised separately to contextualise feasibility, reporting, ethics, and governance. EMA studies more often assessed adjacent self-evaluative constructs, including context-linked self-appraisal bias, conviction, and self-report–context mismatch in daily life, whereas task-based studies more directly assessed confidence–accuracy calibration and feedback updating. Across EMA studies, greater momentary symptom severity and more restricted contexts were often associated with inflated self-evaluations and divergence from observer-rated functioning. Task-based studies indicated that confidence calibration and feedback utilisation may diverge from objective performance; in performance-controlled paradigms, some studies reported comparable metacognitive sensitivity/efficiency, but the overall evidence remains uncertain. Passive sensing was common in psychosis research but was rarely explicitly tied to metacognitive constructs. Conclusions: Current digital work spans both core metacognitive monitoring constructs and adjacent self-evaluative/insight-related constructs, rather than a single unitary construct. Clinical translation remains hypothesis-generating: interpretability may be improved by combining clinical anchors, low-burden EMA, and optional contextual streams, but thresholds, workflows, and signal-action rules require prospective validation. Full article

Dissolved oxygen (DO) is a primary environmental regulator of shrimp physiology and behavior in intensive aquaculture systems. Whether shrimp acoustic emissions quantitatively reflect oxygen-driven behavioral modulation under operational pond conditions, however, remains uncertain due to the difficulty of isolating biologically relevant signals from complex soundscapes. In this study, passive acoustic monitoring was conducted in commercial outdoor ponds culturing Litopenaeus vannamei. A periodic-coding non-negative matrix factorization approach was applied to separate putative shrimp-associated acoustic components from broadband background noise and to obtain stable time–frequency representations of acoustic activity. Temporal variations in the extracted acoustic intensity were compared with simultaneously measured DO concentrations. Rather than relying on global correlation, phase-specific analyses revealed that the putative shrimp-associated acoustic component exhibited consistent positive associations with DO dynamics during both rising and declining phases, whereas background noise showed only weak and non-coherent relationships with DO. These results indicate that the observed acoustic–oxygen relationship is non-stationary and context-dependent. Given the observational nature of the study and potential confounding influences (e.g., aeration and other environmental factors), these findings, which are based on observations from a single pond over a limited recording period (62.85 h) under specific operational conditions, should be interpreted with caution and regarded as a proof-of-concept rather than evidence of general applicability. Nevertheless, the results are consistent with the hypothesis that population-level acoustic activity may reflect environmentally modulated behavioral responses. This highlights the potential of soundscape-based approaches as non-invasive tools for supporting aquaculture monitoring, while emphasizing the need for further validation under controlled and multi-site conditions. Full article

Exposure to road traffic noise is an increasing public health concern in developing countries. However, limited research has explored its effect on children’s cognitive function in contexts with common lifestyles and socioeconomic conditions in these countries. This study aims to evaluate the association between residential outdoor traffic noise exposure in Sincelejo, Colombia, the multidimensional poverty index (MPI) and the effects on cognitive functions in children with a cross-sectional deisgn. Noise levels were estimated using the CNOSSOS model and spatially linked to selective attention and working memory of children, assessed with standardized cognitive tests. Associations were estimated with logistic regression models adjusted for sociodemographic and school characteristics and stratified by MPI. Sensitivity analyses were conducted to evaluate the consistency of the associations. The results indicated a statistically significant yet weak association between a 1 dBA increase in noise levels and reduced processing speed (≤95) in selective attention tasks, particularly in the area with the highest prevalence of MPI < 50. However, sensitivity analyses did not corroborate these findings, and the observed association should therefore be interpreted with caution as exploratory and hypothesis generating. Full article

Background/Objectives: Gastrointestinal bleeding after metabolic bariatric surgery is a relatively rare adverse event, but it has significant morbidity potential. The clinical course can be rapidly unfavorable, requiring early recognition and prompt intervention. The management of this complication often involves different approaches, surgical or endoscopic, the use of which is influenced by the particularities of the postoperative anatomy and the timing of the bleeding. This study aimed to evaluate the incidence, clinical characteristics, and factors associated with postoperative bleeding following bariatric surgery. Methods: A retrospective observational study was conducted on patients who underwent bariatric surgery between 2012 and 2025 at a single tertiary center. During this period, 1010 bariatric procedures were performed. Of these, 68 patients developed postoperative complications and 24 experienced postoperative bleeding. Postoperative bleeding was defined as a hemoglobin drop > 2 g/dL and/or clinically evident bleeding requiring intervention. As bleeding represents a specific subtype of postoperative complication, all statistical analyses were restricted to patients with documented complications. Results: Among the 68 patients with postoperative complications, 24 (35.3%) developed postoperative bleeding. In this exploratory analysis, male sex showed a signal suggestive of association with postoperative bleeding (OR: 9.69, p = 0.005); however, this finding should be interpreted as hypothesis-generating given the study design and the analysis’s being restricted to patients with complications. Given the limited number of bleeding events, effect estimates should be interpreted cautiously. In an exploratory multivariate model, dyslipidemia was associated with increased odds of bleeding (OR: 19.90, p = 0.047), while hepatomegaly and male sex showed positive but non-significant associations. Conclusions: Among patients who developed postoperative complications after bariatric surgery, male sex emerged as a potential signal associated with postoperative bleeding in this exploratory analysis. These findings should be interpreted as hypothesis-generating rather than definitive predictors and require validation in larger cohorts. Dyslipidemia and hepatomegaly emerged as potential associated factors in exploratory analyses, but these findings require confirmation in prospective and multicentric studies. Full article