Search Results (63,539)

Background: Psychosis is a common neuropsychiatric symptom associated with Parkinson’s disease (PD), with prevalence rates of up to 75% over the course of the disease. Parkinson’s disease psychosis (PDP) is associated with increased morbidity, caregiver burden, depression, poorer quality of life and progression of dementia. It has also been shown to be a strong predictive factor for long-term care placement, and results in up to 71% increase in risk of mortality compared with PD patients free from psychotic symptoms. Use of APs for PDP is common, with up to 35% of PD patients prescribed at least one AP within 7 years of PD diagnosis. Methods: Four electronic databases (Ovid MEDLINE, Embase, PsycINFO, PubMed) were systematically searched for double-blind, randomised, placebo-controlled clinical trials for the use of APs in the treatment of PDP and their effects on PD motor symptoms, according to PRISMA guidelines. Results: Eleven studies from ten publications were identified and included in this review. Four studies investigated quetiapine, three investigated olanzapine, two investigated clozapine and a further two investigated pimavanserin. Quetiapine showed no significant improvement for PDP over placebo in three of the four studies, with both olanzapine studies also showing no improvement. Olanzapine studies also showed significant motor worsening compared to placebo. Clozapine significantly improved psychosis compared with placebo in both studies, with large effect sizes in primary outcome measures; (−0.82, 95% CI −1.37 to −0.26), −0.89 (95% CI −1.42 to −0.36). Pimavanserin also showed significant improvement (−0.48, 95% CI −0.77 to −0.18). Quetiapine, clozapine and pimavanserin showed no significant worsening in motor scores compared with placebo groups. Conclusions: Data from the studies included in this review suggest that the use of quetiapine for the management of PDP may not be evidence based. Clozapine may improve PDP symptoms with low doses however significant side-effects may limit usability. The findings from this review support the use of clozapine as an alternative AP for the management of PDP when clinically appropriate. Full article

This critical integrative review reassesses the lipid paradigm by systematically mapping 380 influential trials and cohort studies on cholesterol, saturated fats, and statins in relation to cardiovascular and cognitive outcomes. The evidence base reveals a nearly even split between studies supporting and challenging LDL-centric causality, alongside pervasive methodological flaws, including reliance on surrogate lipid markers, ecological inferences, residual confounding, and industry-related reporting biases. Trial-generation comparisons and structured risk-of-bias assessment (ROB 2, ROBINS-I) repeatedly show that substantial pharmacological LDL reductions do not consistently yield proportional reductions in myocardial infarction, stroke, or all-cause mortality. Integrating Mendelian randomization with clinical and metabolomic data, the review advances a Critical Window Hypothesis in which LDL is necessary but not sufficient for atherogenesis, exerting dominant causal influence during early and midlife plaque initiation, while inflammatory, oxidative, and hemodynamic factors become primary drivers in advanced disease. Metabolomic studies of extreme longevity and late-life cohorts demonstrate that bile acids, steroid metabolites, and low-glycemic metabolic profiles—not total cholesterol—better predict survival and cognitive preservation, and that higher LDL in the oldest-old often associates with lower mortality and dementia risk. These findings challenge universal LDL-centric policies and support lifestyle medicine strategies prioritizing systemic metabolic optimization over isolated cholesterol targets. Full article

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology, arising from complex interactions between tumor biology, host factors, and anticancer therapies. Growing evidence indicates that biological sex and gender-related factors modulate both thrombotic risk and clinical expression of venous thromboembolism (VTE) in patients with cancer. In this narrative review, we summarize current epidemiological, biological, and clinical data on sex- and gender-related differences in CAT across solid and hematologic malignancies. Men generally exhibit a higher overall incidence of VTE, whereas women may experience earlier, treatment-associated thrombotic events, with variability according to cancer type, stage, and therapy. Biological factors linked to coagulation and inflammation differ between sexes and may contribute to these patterns, although mechanistic evidence remains incomplete. Sex-related disparities also emerge in treatment-associated complications, including bleeding risk and abnormal uterine bleeding in anticoagulated women of reproductive age. In contrast, evidence for sex differences in oncohematology-associated thrombosis is limited and inconsistent. Gender-related inequalities in clinical trial participation further constrain the interpretation of available data. Overall, current evidence supports sex as a clinically relevant modifier of CAT risk, underscoring the need for systematic sex- and gender-informed research, to improve mechanistic understanding, and sex-stratified reporting to advance precision medicine in thrombosis and oncology. Full article

Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols—and its classes and subclasses—and BC risk—overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))—in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HR_{Q5 vs. Q1} = 1.02; 95% CI: 0.95–1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population. Full article

Sinonasal inverted papillomas (IPs) are rare benign tumors with ~15% postoperative recurrence and a ~8% risk of malignant transformation, with human papillomavirus (HPV) reported as a risk factor in IP malignant transformation. To evaluate clinical, molecular and immunohistochemical factors associated with recurrence and malignant transformation in IPs. We retrospectively analyzed 73 patients with histologically confirmed IPs that were treated at three tertiary ENT centers, including radiologic data, HPV DNA detection and p16 immunohistochemistry. Univariate analysis was used to identify factors associated with recurrence and malignant transformation, and restricted exploratory multivariable logistic regression models were used to assess recurrence while minimizing overfitting. Fourteen recurrences (19%) were associated with longer symptom duration (p = 0.003), smoking (p = 0.03), advanced Krouse stage (III–IV) (p < 0.001), frontal sinus origin (p = 0.02), HPV+ DNA (50% vs. 22%, p = 0.048), and p16 loss/reduced expression (p = 0.006). Nine recurrences transformed into carcinoma (12%) and were associated with smoking (p = 0.01). HPV+ was not associated with malignancy (p = 1.00). Recurrence was associated with the advanced stage of the IP, tobacco use, longer symptom duration, frontal sinus origin, HPV+, and p16 loss/reduced expression. Full article

Land subsidence (LS) is a major global geo-environmental issue that profoundly affects the suitability and safety of land use planning (LUP). However, existing LUP systems generally neglect the dynamic evolution of LS and lack a systematic framework for assessing conflicts between land use and subsidence. To address this gap, this study develops an integrated evaluation framework that combines SBAS-InSAR, GeoDetector, and a spatial conflict detection model. A total of 166 Sentinel-1A images acquired from 2017 to 2024 were processed using SBAS-InSAR to derive the spatiotemporal characteristics of LS. GeoDetector was subsequently applied to identify the dominant driving factors and their interactions. A sensitivity classification scheme for current land use (CLU) and LUP types with respect to LS hazards was then developed, and a spatial conflict detection model was constructed to delineate conflict zones and quantify conflict intensity. Using Huainan City as a case study, the results show the following: (1) from 2017 to 2024, LS was generally characterized by slight or negligible subsidence, with severe subsidence mainly concentrated in coal mining areas; ongoing and recently suspended mines exhibited pronounced LS, whereas early-closed and unmined areas showed an overall uplift trend. (2) LS in Huainan was primarily driven by soil type, annual rainfall, and mining activities, and two-factor interactions generally exhibited enhancement effects. (3) Compared with CLU, LUP has, to some extent, incorporated LS risk considerations and implemented corresponding mitigation measures, although certain areas still insufficiently account for LS risks. (4) The proposed framework demonstrates strong rationality and applicability in LS monitoring, driving factor identification, and spatial conflict assessment, providing scientific support for LS risk management and land use spatial optimization. Full article

Background/Objectives: To examine long-term incidence trends of cervical cancer and corpus uteri cancer in Taiwan from 1995 to 2022, with emphasis on age–period–cohort patterns and regional variation. Methods: Data from the Taiwan cancer registry were analyzed. Age-standardized incidence rates (ASRs) were calculated using the 1976 World Standard Population. Temporal trends were evaluated using Joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Age–period–cohort modeling was applied to assess net drift, cohort effects, and period effects. Subgroup analyses were conducted by geographic region and urbanization level. Results: Cervical cancer incidence declined markedly, with ASRs decreasing from 20.06 to 6.78 per 100,000 women between 1995 and 2022 (AAPC = −4.43%, 95% CI: −5.39 to −3.45). In contrast, corpus uteri cancer incidence increased substantially, with ASRs rising from 2.91 to 17.42 per 100,000 women (AAPC = 6.32%, 95% CI: 5.86–6.78). Age–period–cohort analysis revealed a negative net drift for cervical cancer (−5.0% per year) and a positive net drift for corpus uteri cancer (6.1% per year). Cohort effects indicated decreasing cervical cancer risk among women born after 1960, whereas corpus uteri cancer risk increased in successive younger cohorts. Period effects showed pronounced declines in cervical cancer incidence after 2000, patterns that are compatible with the implementation of organized screening, while corpus uteri cancer continued to rise. Conclusions: Cervical cancer incidence in Taiwan has declined substantially over the past three decades, a pattern that is compatible with the long-term impact of organized screening programs. In contrast, the increasing burden of corpus uteri cancer may be associated with generational shifts in metabolic and reproductive risk factors. Full article

Background: The relationship between testosterone and coronary artery disease (CAD) remains a subject of debate. Most studies suggest an inverse association—lower testosterone, higher risk. However, data from Central European populations undergoing coronary angiography are limited. Objectives: To investigate the association between serum testosterone levels and angiographically confirmed coronary artery stenosis in a Slovak population. Methods: This cross-sectional study included 129 consecutive stable patients (84 men, 45 women; mean age 64.3 ± 9.7 years) undergoing elective coronary angiography for suspected stable coronary artery disease. Significant coronary stenosis was defined as ≥50% luminal narrowing in any major epicardial vessel. Serum testosterone, lipid profile, and traditional risk factors were assessed. Univariate and multivariate logistic regression models were constructed to evaluate independent associations of coronary stenosis. Results: Coronary stenosis ≥ 50% was present in 74 patients (57.4%). Notably, patients with stenosis had significantly higher testosterone levels (6.62 ± 2.79 vs. 4.85 ± 3.50 ng/mL, p = 0.002). In univariate analysis, testosterone showed a significant association (OR 1.197 per ng/mL, OR 1.784 per SD, p = 0.003). In multivariate analysis adjusted for age, sex, diabetes mellitus, and LDL (low-density lipoprotein) cholesterol, testosterone remained independently associated (adjusted OR 2.043 per SD, 95% CI 1.221–3.420, p = 0.007), as did diabetes mellitus (OR 2.60, p = 0.032). Conclusions: Elevated serum testosterone is paradoxically associated with increased prevalence of coronary stenosis in our cohort. These findings from stable, chronic CAD patients may work fundamentally differently from what is observed in acute coronary syndromes, where stress-induced testosterone suppression may confound observed associations. Full article

Background: Continuity of care for rheumatoid arthritis patients within regional networks enables stable long-term clinical data collection, despite chronic rheumatologist shortages in Japan. We determined 5-year drug survival and discontinuation reasons for eight biological disease-modifying antirheumatic drugs (bDMARDs) using a regional multicenter registry. Methods: We retrospectively analyzed 1182 patients initiating their first (naïve, n = 784) or subsequent (switch, n = 398) bDMARD between May 2001 and August 2022 across five institutions. The primary endpoint (5-year drug survival) and secondary endpoints (discontinuation risk factors and cumulative incidence of reasons) were evaluated using Kaplan–Meier curves, Cox proportional hazards, and Fine & Gray models. Results: Baseline characteristics varied significantly among bDMARDs. Five-year drug survival in the naïve cohort ranged from tocilizumab (50.8%) to golimumab (22.6%); in the switch cohort, from abatacept (42.6%) to infliximab (10.0%). In multivariable Cox analysis of naïve patients, male sex (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.09–2.02), lower baseline 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) (HR = 0.90, 95% CI = 0.82–0.99), and absence of methotrexate co-therapy (HR = 0.73, 95% CI = 0.55–0.97) predicted discontinuation. The lower baseline DAS28-ESR association potentially reflects successful courses toward intentional cessation following remission. Discontinuations were attributed to inadequate response (27.1%), non-adverse events (25.3%), and adverse events (17.3%). Conclusions: Tocilizumab and abatacept demonstrated the highest retention rates in biologic-naïve and switch cohorts, respectively. Early, individualized drug selection and dose optimization are crucial to maximizing long-term bDMARD effectiveness before switching. Full article

Background/Objectives: In the United States, adult human papillomavirus (HPV) vaccination coverage remains low at 20–50%, depending on age, and cervical cancer (CC) screening rates range from 68 to 76%. Few studies have evaluated characteristics of women who are both HPV vaccinated and up to date (UTD) with screening as an integrated outcome. The purpose of the present study was to classify women into four prevention categories and examine factors associated with being double protected compared to unprotected. Methods: Data were gathered via an online survey from a sample of low-income women (household income < USD 50,000) provided by a research survey company (n = 719). Women were classified into four categories: vaccinated only, screened only, both vaccinated and screened (double protected), or neither (unprotected). Sociodemographic characteristics, healthcare access, and Health Belief Model constructs were assessed. Multivariable logistic regression compared women who were double protected with those unprotected (n = 274). Results: Most women were UTD with screening only (57.8%), while 15.5% were double protected and 22.6% were unprotected. Younger age (Odds Ratio [OR = 0.93; 95% Confidence Interval [CI]: 0.89, 0.98), having ≥1 medical visit in the past year (OR = 4.16; 95% CI: 1.74, 9.95), higher perceived CC risk (OR = 3.65; 95% CI: 1.41, 9.43), greater perceived benefits of CC screening (OR = 1.96; 95% CI: 1.45, 2.66), and higher HPV knowledge (OR = 1.09; 95% CI: 1.01, 1.17) were associated with higher odds of being double protected. Conclusions: A substantial proportion of low-income women lack comprehensive CC prevention. Integrated, bundled prevention strategies that simultaneously promote HPV vaccination and screening may be important to reduce CC disparities. Full article

Objective: To develop and validate a multidimensional nomogram for predicting 28-day all-cause mortality in patients with post-traumatic acute respiratory distress syndrome (ARDS). Methods: A retrospective analysis was conducted on 667 post-traumatic ARDS patients from the MIMIC-IV database, divided into training (n = 466) and validation (n = 201) cohorts (7:3). LASSO regression combined with the Boruta algorithm was used to screen variables and construct a nomogram. Model performance was evaluated by AUROC, calibration curves, and decision curve analysis (DCA) with SHAP analysis to identify core predictors. Results: Ten variables (e.g., lactate, platelet transfusion units, D-dimer) were selected and used to construct the nomogram model. The nomogram showed superior discriminative ability (AUROC = 0.848 in training set, 0.846 in validation set) compared with SOFA, APACHE II scores, and machine learning models (XGBoost, random forest). Calibration curves confirmed good agreement between predicted and actual risks, and DCA indicated better clinical net benefit. SHAP analysis identified lactate and platelet transfusion units as core risk factors and albumin and base excess trauma as protective factors. Conclusions: The nomogram has excellent predictive efficacy and interpretability, providing a reliable tool for clinical intervention in post-traumatic ARDS patients. Full article

Background/Objectives: Prophylactic mastectomy can significantly reduce the risk of breast cancer in patients carrying gene mutations such as BRCA1 and BRCA2. Patients who opt for breast removal are offered tailored reconstructive options based on their medical history and prior treatments, and in these often young patients with limited autologous tissue reserves, implant-based reconstruction is frequently the option of choice. Complication rates of these procedures are relatively high and account for up to 30%. Subcutaneous mastectomy with primary implant reconstruction carries risks such as hematoma, seroma, skin necrosis, necrosis of the nipple–areola complex, and wound healing issues, which may necessitate revision surgery. This university-center retrospective analysis aims to improve outcomes by identifying patient- and surgery-related risk factors associated with postoperative complications in allogenic breast reconstruction following subcutaneous mastectomy. Methods: We analyzed 61 female patients and 122 breasts who underwent primary implant-based reconstruction after skin- or nipple-sparing subcutaneous mastectomy over three years between January 2021 and December 2023. Demographic and surgical variables were systematically collected and analyzed. Results: The mean patient age was 41.5 ± 10.3 years. A total of 13% of patients were active smokers, and 1.6% had diabetes mellitus. Overall, skin flap necrosis occurred in 27.9% of patients (22.1% of breasts), wound healing disorders in 19.7% of patients, wound infections in 9.8%, and revision surgery in 18.0%. A history of pregnancy was associated with skin flap necrosis (OR 10.07, 95% CI 1.79–190.06; p = 0.032); however, this finding must be interpreted with caution due to limited statistical power and model instability. Conclusions: This investigation revealed clinically relevant patterns suggesting potential risk factors for wound healing disorders and skin necrosis. Prospective studies are planned to further substantiate these findings and to help reduce overall complication rates associated with the procedure. Full article

Periodontal disease and oral squamous cell carcinoma (OSCC) are highly prevalent conditions that contribute substantially to global morbidity, as documented by recent Global Burden of Disease analyses. The growing epidemiologic and experimental literature has prompted interest in potential links between chronic periodontal dysbiosis—particularly infection with Porphyromonas gingivalis—and molecular pathways involved in oral carcinogenesis, including β-catenin signaling. This narrative review synthesizes epidemiologic, clinical, and experimental studies examining associations between periodontal disease, P. gingivalis, and OSCC, with focused evaluation of β-catenin as a context-dependent signaling component within broader inflammatory and metabolic networks. Population-based studies report heterogeneous associations between periodontitis and OSCC that are frequently confounded by tobacco use, alcohol consumption, and socioeconomic factors, supporting correlation rather than causal inference. Experimental investigations in vitro and in vivo demonstrate that P. gingivalis can influence β-catenin availability and transcriptional activity through noncanonical mechanisms, including junctional disruption, proteolytic interference with regulatory complexes, and interaction with inflammatory, immune, and metabolic pathways. However, these findings derive largely from simplified model systems and should be interpreted as biologically plausible rather than definitive for human disease. Rather than acting as a dominant oncogenic driver, β-catenin appears to function as an integrative signaling node within a complex network shaped by chronic microbial and inflammatory stress. The principal contribution of this review lies in critically integrating dispersed evidence across study types while explicitly distinguishing association, mechanistic plausibility, and causality. Future longitudinal human studies and mechanistically informed experimental models are required to clarify whether modulation of periodontal dysbiosis or associated signaling pathways has relevance for OSCC risk assessment or prevention. Full article

Background: Chronic stress is associated with dysregulation of the body’s allostatic systems, contributing to increased allostatic load (AL) and adverse metabolic outcomes. Regular physical activity (PA) is considered a key protective factor that may attenuate AL by enhancing adaptive stress responses and supporting metabolic health. This study examined the differences between PA, primary mediators of AL, and metabolic risk markers in apparently healthy adults in Germany. Methods: Forty-six adults (18–45 years) were categorized into a moderate intensity (regular PA: ≥150 min a week vs. non-regular PA: ≤150 min a week) group according to current PA recommendations. Primary AL mediators were quantified by cortisol (μg/12 h), epinephrine (μg/12 h), norepinephrine (μg/12 h), and dehydroepiandrosterone sulfate (DHEA-S: μg/mL). Group differences in primary AL mediators and metabolic risk markers were examined using the Mann–Whitney U test. Results: A significant group difference was observed for cortisol levels, with higher values in the regular PA group (p = 0.01), with a moderate negative effect size of r = −0.38. No statistically significant differences (p > 0.05) were found between groups for epinephrine, norepinephrine, DHEA-S, or metabolic risk markers, including triglycerides, blood pressure, body mass index (BMI), and high-density lipoprotein cholesterol (HDL-C). Conclusions: The findings suggest that regular PA may be associated with altered stress-regulatory activity, as reflected by differences in cortisol. While no statistically significant group differences were observed for metabolic risk markers, descriptive patterns indicate more favorable lipid profiles and potential variation in primary AL mediators at higher PA levels. Given the exploratory nature of the analyses and the small and unequal group sizes, these findings should be interpreted with caution and warrant confirmation in future studies with larger and more balanced samples. Full article

Overtourism has intensified socio-environmental pressures in popular destinations, raising concerns about ethical responsibility and sustainable behavior among tourism actors and visitors. In this study, we explored how environmental awareness and ethical values shape behavioral intentions under overtourism pressure by combining a systematic literature review with qualitative field data from Bali. Through a PRISMA-based review of 100 peer-reviewed journal articles published between 2015 and 2024, we synthesized evidence on environmental ethics, responsible tourism, and pro-environmental behavioral mechanisms. The review reveals that increasing scholarly attention is being paid to ethical norms, emotional engagement, and contextual constraints but shows that there is limited empirical understanding of how these factors are experienced in practice by local actors and domestic tourists. To address this gap, qualitative interviews were conducted with three key stakeholders, including accommodation and tourism service providers, and 10 domestic tourists. Thematic analysis identifies three interrelated mechanisms influencing behavioral intention: (a) recognition of environmental risk and destination vulnerability, (b) ethical reasoning and sense of collective responsibility, and (c) structural barriers shaped by convenience, economic pressures, and weak governance. While participants express strong environmental awareness and moral concern, behavioral intentions are often constrained by limited information, the perceived ineffectiveness of individual actions, and a lack of regulatory enforcement. This study contributes to the sociological literature on sustainable tourism by elucidating how ethics and awareness translate into intention under overtourism pressure. We report the practical implications for ethical communication, stakeholder collaboration, and participatory governance. Full article