Search Results (2,275)

Background: A growing body of evidence suggests that diet can modify Parkinson’s disease (PD) outcomes, although there is disagreement about what should be included and excluded in such a diet. Existing evidence suggests that adherence to the MIND and Mediterranean (MEDI) diets are associated with reduced PD symptoms, but only a few variables from the adherence scales are responsible for the statistically observed improvement. Objectives: The goal was to use patient-reported outcomes in a large cohort to identify the foods and dietary patterns (PRO diet) most strongly associated with the fewest PD symptoms over time, and to develop a composite adherence scale to enable comparisons between MEDI, MIND, and PRO. Methods: Data were obtained from the prospective longitudinal natural history study and from Modifiable Variables in Parkinsonism (MVP)—a study designed to identify behaviors associated with patient-reported outcomes (PRO-PD). Upon the completion of the binary and food frequency data collection, using various predictive models and considering congruence with historical data, the PRO diet was created via an iterative process. Our goal was to create a new scale and compare its performance to the existing MIND and MEDI scores. The comparison was made at baseline, using the regression models for PRO-PD and the different scales as the predictors. The models were compared via the Akaike Information Criterion (AIC). To examine whether baseline adherence levels predicted subsequent symptom trajectories, the baseline PRO diet adherence and subsequent slope of progression were evaluated. Results: Data from 2290 individuals with PD were available for this analysis. The Mediterranean and MIND diets showed almost identical effects. For both the diets, the effect they had on non-motor symptoms was about twice the effect on motor symptoms. The slopes for the total PRO-PD for MEDI, MIND, and PRO-21 were −64.20467, −64.04220, and −28.61995, respectively. The AIC value differences were substantial (>2), indicating meaningful improvements in the model fit for total PRO-PD, as follows: MEDI: 28,897.24, MIND: 28,793.08, and PRO-21: 27,500.71. The subset of individuals who were most adherent to the PRO-21 diet at baseline had the slowest subsequent progression, as measured by a 43% reduced PRO-PD slope, compared to the less adherent groups. Conclusions: The PRO-21 outperformed the MIND and MEDI diets in the model fit, overcoming the ceiling effects and showing orders of magnitude and superior explanatory power for variance in PD outcomes, despite the smaller per-unit effect sizes. However, its rigorous demands may introduce barriers related to cost, feasibility, and sustainability, underscoring the need for future intervention trials to assess real-world feasibility, adherence, side effects, and clinical impact. Full article

Objective: The present review aims to compare the oral microbial profile (OMP) of patients undergoing fixed orthodontic therapy (OT) versus clear aligner therapy (CAT) for the treatment of malocclusions. Methods: Clinical studies were included. Case-reports/-series, letters to the editor, reviews, perspectives, and expert opinions were excluded. Indexed databases (MEDLINE/PubMed, Embase, Scopus, and Web of Science) were searched up to the end point of May 2025, without time and language barriers. The study was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The risk of bias (RoB) and quality of evidence were assessed. Results: Three randomized clinical trials (RCTs) and seven non-RCTs were included. In all RCTs and five non-RCTs, OMP was assessed using subgingival plaque samples. Periodontopathogenic bacteria and Gram-negative anaerobic microbes were more often identified in patients undergoing fixed OT than CAT. The biofilm mass was higher in patients undergoing fixed OT than CAT. In two RCTs, periodontopathogenic bacteria were dominant among patients undergoing fixed OT than CAT. All RCTs and two non-RCTs had a high RoB. The certainty of evidence was “moderate” in 70% of the studies. Conclusions: Due to a high RoB, variability in study designs, and lack of power analysis, direct comparisons remain limited. Full article

Background/Objectives: Accurate determination of malignancy in pancreatic masses through endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is crucial for appropriate clinical management and prognostic assessment. However, the diagnostic sensitivity of conventional cytology using Papanicolaou (Pap) staining remains limited, often leading to inconclusive results. In this study, we investigated the diagnostic utility of methionyl-tRNA synthetase 1 (MARS1) through immunohistochemical (IHC) and immunofluorescence (IF) staining as a potential biomarker for pancreatic cancer. IHC analysis was conducted on resected tissue samples from 10 patients, including both pancreatic ductal adenocarcinoma and corresponding non-neoplastic pancreatic tissue. Additionally, cytologic samples were obtained from 198 patients with pancreatic masses who underwent EUS-FNA for diagnostic evaluation. Pap staining and MARS1 IF staining were performed on liquid-based cytology slides derived from EUS-FNA specimens. Results: MARS1 was detected by IHC staining in the 10 surgical specimens diagnosed with pancreatic adenocarcinomas. After Pap staining, 37 patients were excluded because of unsuitable specimens, leaving 161 patients who underwent both Pap and MARS1 IF staining. EUS-FNA specimens from the 151 patients with pancreatic ductal adenocarcinoma were classified by Pap staining as atypia (n = 36), suspicious for malignancy (n = 55), or malignancy (n = 60). MARS1 IF staining was positive in 147 of these patients and negative in 4. MARS1 IF staining distinguished pancreatic cancer in specimens with atypia on Pap staining. The sensitivity for detecting pancreatic cancer was significantly higher for MARS1 IF staining than for conventional Pap staining (97.4% vs. 79.1%, p < 0.0001). Conclusions: The high sensitivity of MARS1 IF staining improved malignancy detection in pancreatic masses. Further prospective studies are required to validate our findings. Full article

Background and clinical significance: Acute reduction in vigilance is a frequent reason for emergency department admissions, especially among the elderly. While intracranial causes or infections with fluid depletion are often responsible, there remain cases where imaging, laboratory tests, and clinical examination fail to provide a clear diagnosis. Case presentation: A 91-year-old woman was presented to the emergency department with recurrent episodes of somnolence to deep coma. On admission, her vital signs were stable, and cerebral CT imaging revealed no intracranial pathology. Laboratory analyses, including blood gas measurements, were unremarkable. Empirical treatment for possible intoxications with benzodiazepines or opioids using flumazenil and naloxone had no effect. An Addison’s crisis was considered but excluded following methylprednisolone administration without improvement in consciousness. Eventually, an isolated elevation of serum ammonia was identified as the cause of the reduced vigilance. Further investigation linked the hyperammonemia to abnormal intestinal bacterial colonization, likely due to a prior ureteroenterostomy. There was no evidence of liver dysfunction, thus classifying the condition as non-hepatic hyperammonemia. Therapy was initiated with rifaximin, supported by aggressive laxative regimens. Ammonia levels and vital parameters were closely monitored. The patient’s condition improved gradually, with serum ammonia levels returning to normal and cognitive function fully restored. Conclusions: This case highlights an uncommon cause of coma due to non-hepatic hyperammonemia in the absence of liver disease, emphasizing the diagnostic challenge when standard evaluations are inconclusive. It underscores the need for broad differential thinking in emergency settings and the importance of considering rare metabolic disturbances as potential causes of altered mental status. Full article

Toenail onychomycosis causes significant problems in public health and is more common among the elderly and immune-compromised populations. A previous culture-based survey of communal finely ground toenails from the east coast of Australia isolated 125 T. interdigitale but only one T. rubrum. This paucity of T. rubrum was surprising because it is one of the most common dermatophytes isolated worldwide. Our aim was to find out if T. rubrum was present but not cultured. DNA was extracted from ground toenails from the same samples. New specific primers were designed for the ITS region of T. rubrum that excluded T. interdigitale and vice versa. PCR with these new primers found T. rubrum as well as T. interdigitale in all ground toenail samples. This suggests that T. rubrum was present and common in the ground toenails. It was possibly missed by culture because it grows slowly and was overgrown by T. interdigitale and non-dermatophyte moulds. Alternatively, its viability may have declined earlier, during collection, treatment, or storage of the ground toenails. This has implications for studies of clinical materials, especially nails, as infection by T. rubrum (the most common dermatophyte) may be missed by culture, the main method used in pathology laboratories. Full article

Background/Objectives: ST-segment deviation (STD) on electrocardiography (ECG) may reflect myocardial injury in critically ill patients. However, its prognostic significance in non-cardiac intensive care unit (ICU) populations remains unclear. We aimed to assess the association between STD on ICU admission and 30-day mortality and to evaluate its incremental prognostic value beyond the SOFA score. Methods: In this retrospective single-center study, we included 307 consecutive ICU patients (median age: 64.0 years; 65.5% men). Patients with acute cardiac conditions were excluded. STD was defined as ≥1 mm ST elevation or depression in any lead on standard 12-lead ECG performed on admission. The primary outcome was 30-day all-cause mortality. Prognostic associations were assessed using multivariable Cox regression adjusted for SOFA score. Discriminative performance was evaluated by comparing ROC curves for models with and without STD, with bootstrap-based testing (1000 iterations) to assess significance. Results: STD was present in 126 patients (41.0%) and occurred more frequently in non-survivors (47.6% vs. 36.5%, p = 0.033. In Cox regression, STD was independently associated with 30-day mortality (HR = 1.534; 95% CI: 1.081–2.177; p = 0.017), even after adjustment for SOFA score. This association remained statistically robust in bootstrap validation. The addition of STD amplitude to the SOFA score modestly improved model discrimination with a borderline significant difference between the areas under the curve (ΔAUC = 0.005, p = 0.0581). Conclusions: ST-segment deviation on the admission ECG is an independent predictor of 30-day mortality in non-cardiac critically ill patients and may enhance risk stratification beyond the SOFA score. Full article

Heart failure (HF) treatment evolved in the last 5 years with the introduction of new agents capable of reducing HF hospitalization and HF-related mortality. However, some categories such as patients with renal dysfunction tend to be excluded from larger randomized clinical trials. Additionally, most patients with HF experienced unavoidable glomerular filtration rate (GFR) deterioration during the clinical course. This is related to both cardio–renal interaction pathways and common cardiovascular risk factors that affect HF and chronic kidney disease (CKD). However, mineralocorticoid antagonists (MRAs) remain a cornerstone of HF therapy regardless of left ventricular ejection fraction (LVEF) values; some concerns remain about their utilization in CKD. Nevertheless, three studies (FIDELIO, FIGARO, and FINEARTS) have recently showed beneficial effects in both patients with HF and CKD associated with diabetes. Notably, finerenone a new non-steroidal MRA represents a significant step forward in cardiovascular therapy; its application spans a wide spectrum of HF phenotypes and CKD stages, and ongoing investigations will further elucidate its role in combination regimens and in broader patient populations. Further study may investigate the role of the drug in patients with heart failure with reduced ejection fraction (HFrEF) and in the severe CKD stage of non-diabetic etiology. In the current review paper, we provide a chronological overview of major trials evaluating the renal outcomes of MRAs, culminating in the emergence of finerenone as a novel therapeutic option for high-risk CKD populations, particularly those with type 2 diabetes mellitus (T2DM). Full article

Electroencephalography (EEG) is a widely used non-invasive method for capturing brain activity, offering valuable insights into cognitive and emotional states relevant to mental health. With the growing complexity and volume of EEG data, machine learning (ML) techniques—particularly deep learning—have become integral in extracting meaningful patterns. While much of the current literature focuses on supervised learning methods that rely on labeled data, unsupervised learning offers an alternative approach capable of discovering hidden structures and novel biomarkers without requiring predefined labels. This systematic review aimed to identify and synthesize recent peer-reviewed research that applied unsupervised or self-supervised learning techniques to EEG data in the context of mental health monitoring, diagnosis, or analysis. A comprehensive search was conducted across six major databases, including PubMed, Scopus, Web of Science, IEEE Xplore, PsycINFO, and Google Scholar, covering literature from January 2018 to March 2025. Following PRISMA guidelines, predefined inclusion and exclusion criteria were applied to screen and assess the relevance and quality of studies. From 512 initial records, 403 unique articles were screened, and 20 underwent full-text review. Ultimately, no studies met all the inclusion criteria. Most were excluded for employing only supervised methods, being review articles, or focusing on non-mental-health applications. The absence of eligible studies highlights a significant gap in current research and emphasizes the need for future empirical work exploring unsupervised techniques in EEG-based mental health applications. Such efforts could pave the way for more scalable, label-free approaches to understanding brain dynamics in psychological conditions. Full article

(1) Background: Physiological responses, such as heart rate and heart rate variability, have been increasingly utilized to monitor, detect, and predict mental stress. This review summarizes and synthesizes previous studies which analyzed the impact of mental stress on heart activity as well as mathematical, statistical, and visualization methods employed in such analyses. (2) Methods: A total of 119 articles were reviewed following the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Non-English documents, studies not related to mental stress, and publications on machine learning techniques were excluded. Only peer-reviewed journals and conference proceedings were considered. (3) Results: The studies revealed that heart activities and behaviors changed during stressful events. The majority of the studies utilized descriptive statistical tests, including t-tests, analysis of variance (ANOVA), and correlation analysis, to assess the statistical significance between stress and non-stress events. However, most of them were performed in controlled laboratory settings. (4) Conclusions: Heart activity shows promise as an indicator for detecting stress events. This review highlights the application of time series techniques, such as autoregressive integrated moving average (ARIMA), detrended fluctuation analysis, and autocorrelation plots, to study heart rate rhythm or patterns associated with mental stress. These models analyze physiological data over time and may help in understanding acute and chronic cardiovascular responses to stress. Full article

During heavy rainfalls, overflowing sewage water flows from the Combined Sewer Overflow (CSO) chambers and pollutes the Trnávka River in Trnava, Slovakia. This paper aims to propose water retention measures for the Trnávka River as a remediation technique for CSO-affected watercourses, which can contribute to the ‘flushing’ of the riverbed. During heavy rainfalls, the Trnávka River is polluted by solid, non-soluble materials, which produce unpleasant odors and are the subject of numerous complaints by citizens, particularly during low water levels. Three inflatable rubber weirs were designed, and their design was verified using a 1D numerical model of the Trnávka River. The simulations of the proposed measures performed in the HEC-RAS 5.0 software excluded the adverse effect of the backwater on the functioning of the CSO chambers in the city of Trnava during normal flow rates and confirmed that, even after installation of the weirs, the transition of the flood wave will pass in the riverbed, not causing the flooding of the adjacent area. The chemical–physical study of the Trnávka River confirmed our assumption that higher flow rates, which can be secured by the regulation of the proposed weirs, can contribute to the purity of the watercourse in the city of Trnava. Full article

Gender-independent, intersex, non-binary, and transgender (GIaNT) youth have puberty health and sex education needs that are different from cisgender youth. Unfortunately, this population has historically been excluded from curricula pertaining to these issues in schools throughout the U.S. and Canada. While sex education programs are limited for all youth, and navigating puberty can range from exciting to scary for all youth, GIaNT youth are particularly vulnerable to facing negative outcomes by being omitted from such curricula. Because they are not able to access adequate information in schools and in their family/friend networks, a majority of GIaNT youth turn to the internet to seek out resources for education on puberty health and sex education. To this end, our team is in the process of creating an online educational resource (OER) that is age-appropriate and affirming for GIaNT youth to be provided with resources that are personalized to users’ unique needs. This literature review discusses content suggestions for inclusion of comprehensive puberty health and sex education that caters to GIaNT youth and their unique needs. Full article

Emerging evidence suggests a significant association between monocytes and the pathophysiology and prognosis of idiopathic pulmonary fibrosis (IPF). This review aims to systematically evaluate current knowledge regarding blood monocyte counts and their relationship with the etiology, progression, and prognosis of IPF. We conducted a systematic search in the PubMed database for articles published through 17 February 2025, using the MeSH terms “lung diseases, interstitial” and “monocytes,” which yielded 314 results. After filtering for full-text articles in English (n = 242), we included only studies focusing on blood monocyte counts with clinical implications in IPF. Articles relating to other cell types or non-IPF lung diseases were excluded. Our systematic search identified 12 relevant articles. Monocytes play an essential role in regulating inflammatory responses and resolution across multiple diseases, with established but incompletely understood contributions to lung fibrosis development in IPF. Correlations have been demonstrated between elevated blood monocyte counts and the following: (1) the presence and progression of interstitial lung abnormalities, (2) the progression from an indeterminate usual interstitial pneumonia (UIP) pattern on CT scans to definitive IPF, and (3) worse lung function parameters, an increased risk of acute exacerbations, and reduced overall survival in IPF patients. Monocytes serve as critical orchestrators throughout IPF’s natural history—from early interstitial changes to disease progression and acute exacerbations. Targeting monocyte recruitment pathways and reprogramming their differentiation represents a promising therapeutic approach, while circulating monocyte counts offer potential as accessible biomarkers for disease progression and treatment response. Future research should characterize stage-specific monocyte phenotypes to enable precision-targeted interventions. Full article

Background/Objectives: Bisphosphonates may influence vascular calcification and atheroma formation via farnesyl pyrophosphate synthase inhibition in the mevalonate pathway regulating bone and lipid metabolism. However, the clinical impact of NCB use on cardiovascular outcomes remains uncertain, largely due to methodological heterogeneity in prior studies. We aimed to evaluate the association between nitrogen-containing bisphosphonate (NCB) therapy and coronary artery calcium (CAC) progression, as well as the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) events. Methods: From 6814 participants in MESA Exam 1, we excluded males (insufficient male NCB users in the MESA cohort), pre-menopausal women, baseline NCB users, and users of hormone replacement therapy, raloxifene, or calcitonin. Among 166 NCB initiators and 1571 non-users with available CAC measurements, propensity score matching was performed using the available components of FRAX, namely age, race, BMI, LDL cholesterol, alcohol, smoking, and steroid use, and baseline CAC yielded 165 NCB initiators matched to 473 non-users (1:3 ratio). Linear mixed-effects models evaluated CAC progression, and Cox models analyzed incident CVD and CHD events. Results: In the overall cohort, NCB use was not significantly associated with CAC progression (annual change: −0.01 log Agatston units; 95% CI: −0.05 to 0.01). However, among participants with a baseline estimated glomerular filtration rate (eGFR) < 65 mL/min/1.73 m², NCB use was associated with attenuated CAC progression compared with non-users (−0.06 log Agatston units/year; 95% CI: −0.12 to −0.007). No significant association was observed between NCB use and incident CVD events in the overall cohort (HR: 0.90; 95% CI: 0.60−1.36) or within kidney function subgroups. Conclusions: Incident NCB use among postmenopausal women with mild or no CAC at baseline was associated with reduced CAC progression only in women with impaired kidney function. However, this association did not correspond to a decreased risk of subsequent cardiovascular events, suggesting that the observed imaging benefit may not translate into meaningful clinical association. Full article

Objective: This retrospective study aims to evaluate the effect of copper intrauterine device (Cu-IUD) use on the adequacy and diagnostic quality of endometrial biopsy specimens in women with abnormal uterine bleeding (AUB). Patients with levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. The study compares the histopathological adequacy of endometrial samples between Cu-IUD users and non-users, highlighting potential interpretation challenges in routine pathological assessment. Methods: The study was conducted on 409 women aged 25–55 who presented with abnormal uterine bleeding (AUB) to the Gynecology and Obstetrics Outpatient Clinic at Kayseri City Hospital between 1 April 2021 and 1 April 2023. The patients were divided into two groups: copper IUD (Cu-IUD) users (n = 215) and non-IUD users (n = 194). Patients using levonorgestrel-releasing intrauterine systems (LNG-IUS, e.g., Mirena) were excluded from the study. Endometrial biopsies were obtained using the Pipelle curette technique without anesthesia, preserved in 10% formalin, and assessed for pathological classification and diagnostic adequacy. Results: The proportion of unclassifiable pathological categories was significantly higher in copper IUD users (63.93%) compared to non-IUD users (36.05%) (p = 0.013). Additionally, a negative correlation was observed between pathological category and endometrial thickness (r = −0.3147, p < 0.001), suggesting that thinner endometrial lining may reflect atrophic or diagnostically ambiguous tissue patterns. However, no significant association was found between IUD use and endometrial thickness (p = 0.073). Conclusions: The findings indicate that copper IUD use may affect the diagnostic adequacy of endometrial biopsy specimens, likely due to inflammatory or structural changes in the endometrium. These results underline the importance of considering IUD-related alterations when interpreting biopsy findings. Further research is needed to refine diagnostic approaches and better understand the clinical implications of these effects. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease worldwide, driven by the global epidemics of obesity, type 2 diabetes, and metabolic syndrome. In this evolving nosological landscape, alcohol consumption—traditionally excluded from the diagnostic criteria of non-alcoholic fatty liver disease (NAFLD)—has regained central clinical importance. The recently defined MetALD phenotype acknowledges the co-existence of metabolic dysfunction and a significant alcohol intake, highlighting the synergistic nature of their pathogenic interactions. This narrative review provides a comprehensive analysis of the biochemical, mitochondrial, immunometabolic, and nutritional mechanisms through which alcohol exacerbates liver injury in MASLD. Central to this interaction is cytochrome P450 2E1 (CYP2E1), whose induction by both ethanol and insulin resistance enhances oxidative stress, lipid peroxidation, and fibrogenesis. Alcohol also promotes mitochondrial dysfunction, intestinal barrier disruption, and micronutrient depletion, thereby aggravating metabolic and inflammatory derangements. Furthermore, alcohol contributes to sarcopenia and insulin resistance, establishing a bidirectional link between hepatic and muscular impairment. While some observational studies have suggested a cardiometabolic benefit of a moderate alcohol intake, emerging evidence challenges the safety of any threshold in patients with MASLD. Accordingly, current international guidelines recommend alcohol restriction or abstinence in all individuals with steatotic liver disease and metabolic risk. The review concludes by proposing an integrative clinical model and a visual cascade framework for the assessment and management of alcohol consumption in MASLD, integrating counseling, non-invasive fibrosis screening, and personalized lifestyle interventions. Future research should aim to define safe thresholds, validate MetALD-specific biomarkers, and explore the efficacy of multidisciplinary interventions targeting both metabolic and alcohol-related liver injury. Full article