Search Results (1,832)

In today’s world, unhealthy living habits have contributed to the rise in metabolic disorders like hyperlipidemia. Recognized as a popular edible and medicinal mushroom in China and various eastern nations, Ganoderma lucidum is a promising high-value functional and medicinal food with multiple biological activities. Our earlier research has demonstrated that G. lucidum polysaccharides (GLP) showed distinct lipid-lowering abilities by enhancing the response to oxidative stress and inflammation, adjusting bile acid production and lipid regulation factors, and facilitating reverse cholesterol transport through Nrf2-Keap1, NF-κB, LXRα-ABCA1/ABCG1, CYP7A1-CYP27A1, and FXR-FGF15 pathways, hence we delved deeper into the effects of GLP on hyperlipidemia, focusing on its structural characterization, gut microbiota, and fecal metabolites. Our findings showed that GLP changed the composition and structure of gut microbiota, and 10 key biomarker strains screened by LEfSe analysis markedly increased the abundance of energy metabolism, and cell growth and death pathways which were found by PICRUSt2. In addition, GLP intervention significantly altered the fecal metabolites, which enriched in amino acid metabolism and lipid metabolism pathways. The results of structural characterization showed that GLP, with the molecular weight of 12.53 kDa, consisted of pyranose rings and was linked by α-type and β-type glycosidic bonds, and its overall morphology appeared as an irregular flaky structure with some flecks and holes in the surface. Collectively, our study highlighted that the protective effects of GLP were closely associated with the modification of gut microbiota and the regulation of metabolites profiles, thus ameliorating dyslipidemia. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene (OPRM1) promoter methylation, play a role in this dysfunction. Using a repeated-measures design, 28 ME/CFS/FM patients and 26 matched healthy controls visited the hospital twice within four days. Assessments included blood sampling for epigenetic analysis, a clinical questionnaire battery, and quantitative sensory testing (QST). Global DNA (hydroxy)methylation was quantified via liquid chromatography–tandem mass spectrometry, and targeted pyrosequencing was performed on promoter regions of OPRM1, COMT, and BDNF. ME/CFS/FM patients reported significantly worse symptom outcomes. No differences in global (hydroxy)methylation were found. Patients showed significantly higher OPRM1 promoter methylation, which remained after adjusting for symptom severity and QST findings. Across timepoints, OPRM1 methylation consistently correlated with BDNF Promoter I and Exon III methylation. This is, to the best of our knowledge, the first study examining OPRM1 methylation in ME/CFS/FM. Increased OPRM1 methylation in patients, independent of symptoms or pain sensitivity measures, supports the hypothesis of dysregulated opioidergic signaling in these conditions. Full article

Background/Objectives: Acute sinusitis (AS) is a common infection of the upper respiratory tract that places considerable clinical and economic burden worldwide. Although frequently encountered in practice, the factors that predispose individuals to AS remain poorly understood. This study examined how different respiratory disorders and comorbidities influence the likelihood of developing AS, aiming to clarify its underlying risk profile. Methods: A longitudinal analysis was performed using electronic health records from the Clinical Center of the University of Debrecen Hospital. The study cohort (2007–2022) encompassed 37,164 observations. To evaluate the risk of AS progression, Log-Rank tests and Cox proportional hazards regressions were applied whilst adjusting for covariates. Results: The risk of developing AS was significantly higher among individuals with preceding respiratory conditions. Patients with common cold demonstrated a 2.3-fold increased risk of developing AS (95% CI [1.51–3.40]). Compared to those without such disorders, participants with acute bronchitis had a 2.5-fold higher hazard of AS (95% CI 1.90–3.26). The strongest association was observed for allergic rhinitis (HR = 4.04, 95% CI 3.18–5.13), followed by chronic sinusitis (HR = 3.10, 95% CI 2.13–4.51). Chronic obstructive pulmonary disease was also identified as a significant predictor for AS (HR = 1.62, 95% CI 1.04–2.52), whereas dental pathologies were associated with a modest protective effect (HR = 0.69, 95% CI 0.48–0.97). Conclusions: Patients with allergic rhinitis, chronic sinusitis, acute bronchitis, common cold, or chronic obstructive pulmonary disease have a markedly higher risk of developing AS. Clinicians should actively screen for these conditions when assessing patients with recurrent or severe sinus infections. Early recognition and management of underlying respiratory disorders may reduce AS episodes, promote symptom control, and lessen healthcare burdens. Future research should concentrate on precision medicine to leverage AS preventive and management strategies. Full article

New wearable technology opens new possibilities for low-cost, easily accessible home-based interventions as a supplement to typical clinical rehabilitation therapy. In this pilot study, we tested a new interactive adjustable Feedback training system on 14 infants at high risk of cerebral palsy between 2 and 12 months of age to facilitate increased movements. The system consists of four wireless motion sensors placed on the infant’s limbs. Inertial sensors track the infant’s movements which control auditory and visual stimuli that act as motivational feedback. A 15 min usage of the Feedback training system four days a week for approximately six months was aimed for. None of the participants reached the recommended amount of intervention, due to time limitations. Seven of the twelve participating infants (58%) achieved at least 50% of the recommended training amount. Parents found the Feedback training system easy to use with minimal need for technical assistance. Preliminary data suggest that infants engaged more actively during training sessions where their movements actively controlled the presentation of the stimuli. The Feedback training system is promising as a user-friendly add-on to the playful and interactive stimulation of motor and cognitive development in infants with neurodevelopmental disorders. Full article

Background/Objectives. Chronic benzodiazepine (BDZ) use is frequently maintained beyond recommended durations due to neuroadaptation, psychological dependence, and withdrawal-related issues. Passiflora incarnata L., herba (P. incarnata) has shown anxiolytic and GABAergic activity that may mitigate withdrawal symptoms, while cognitive-behavioural therapy (CBT) targets maladaptive beliefs and behaviours sustaining BDZ misuse. This study investigates the independent and interactive effects of P. incarnata and CBT on BDZ dose reduction during a three-month tapering program. Methods. This retrospective observational study included 186 outpatients with anxiety or depressive disorders in clinical remission undergoing BDZ tapering, of whom 93 received a dry extract of P. incarnata as adjunctive treatment and 93, matched for diagnosis, age and sex, followed a standard tapering protocol. BDZ doses were assessed at baseline and three months. CBT was recorded as a binary variable based on the information documented in the medical records. An ANCOVA was performed to assess the impact of CBT and P. incarnata on BDZ reduction (change in mg diazepam equivalents), adjusting for sex, age, education, baseline anxiety and depression scores, initial BDZ and antidepressant dosage. A subgroup analysis was conducted to investigate the role of P. incarnata dosage in BDZ reduction. Results. Both CBT and P. incarnata were associated with significantly greater reductions in BDZ dosage at three months (CBT: p = 0.005, effect size: 0.032; P. incarnata: p < 0.001, effect size: 0.128). A significant interaction between CBT and P. incarnata was also observed (p = 0.037, effect size: 0.018), indicating a synergistic effect when both interventions were combined. Baseline sociodemographic characteristics, BDZ and antidepressant dosage and symptom severity did not differ significantly between groups. Patients taking 400–600 mg of P. incarnata dry extract showed a higher BDZ reduction compared to those taking 200 mg. Conclusions. These findings suggest that P. incarnata and CBT exert independent yet complementary effects in supporting BDZ tapering. Their combination appears to enhance dose reduction beyond either intervention alone, supporting a multimodal approach that addresses both neurobiological and psychological components of BDZ addiction. Prospective controlled studies are needed to confirm these results and to clarify their impact on long-term discontinuation outcomes. Full article

Background/Objectives: Single-sided deafness (SSD) impairs speech perception, reduces spatial hearing, decreases quality of life, and is frequently accompanied by tinnitus. Cochlear implantation (CI) has become an established treatment option, but long-term prospective evidence across multiple functional and psychological domains remains limited. This study investigated auditory performance, subjective hearing outcomes, tinnitus burden, and psychological well-being over a two-year follow-up in a large SSD cohort. Methods: Seventy adults with SSD underwent unilateral CI. Assessments were conducted preoperatively and at 6 months, 1 year, and 2 years postoperatively. Outcome measures included the Freiburg Monosyllable Test (FS), Oldenburg Inventory (OI), Nijmegen Cochlear Implant Questionnaire (NCIQ), Tinnitus Questionnaire (TQ), Perceived Stress Questionnaire (PSQ), Generalized Anxiety Disorder scale (GAD-7), and General Depression Scale (ADS-L). Longitudinal changes were analyzed using Wilcoxon signed-rank tests with effect sizes; Holm-adjusted p-values were applied for baseline-to-follow-up comparisons. Results: Speech perception improved markedly within the first 6 months and remained stable through 2 years, with large effect sizes. All OI subdomains demonstrated early and sustained improvements in subjective hearing ability. Several hearing-related quality-of-life domains assessed by the NCIQ, particularly social interaction, self-esteem, and activity participation, showed medium-to-large long-term improvements. Tinnitus severity decreased substantially, with marked reductions observed by 6 months and maintained thereafter; the proportion of tinnitus-free patients increased at follow-up, although tinnitus symptoms persisted in a substantial subset of participants. Perceived stress was reduced initially at the early follow-up and remained below baseline thereafter. Anxiety and depressive symptoms mostly stayed within nonclinical ranges, showing no lasting changes after adjusting for multiple comparisons. Conclusions: In this prospective cohort, cochlear implantation was associated with durable improvements in auditory outcomes, tinnitus burden, and selected patient-reported quality-of-life domains over two years. Although significant functional and patient-centered improvements were noted, persistent tinnitus and diverse psychosocial outcomes underscore the need for personalized counseling and comprehensive follow-up that incorporate patient-reported outcomes and psychological assessments. Full article

Background: Severe hypertriglyceridemia (SHTG) in children is a rare but clinically significant disorder associated with recurrent acute pancreatitis and substantial morbidity. Early identification and prompt management are essential to prevent pancreatic and systemic complications. Methods: We report the case of an 11-year-old female with a history of xanthogranulomatous pancreatitis who presented with extreme hypertriglyceridemia, with fasting triglyceride levels exceeding 4000 mg/dL. Results: The patient was treated acutely with continuous intravenous aspart insulin (0.1 U/kg/hour) and adjusted 10% glucose infusion, with hourly glucose and potassium monitoring, leading to a rapid and marked reduction in triglyceride levels—55% reduction within the first 24 h, 76% at 48 h, and 82% after 96 h of treatment. No hypoglycemia or other adverse effects were observed. Nutritional management included a low–long-chain triglyceride (LCT) diet enriched with medium-chain triglycerides (MCTs) and omega-3 fatty acids, providing essential calories while minimizing chylomicron production. Over a 12-month follow-up, the patient remained asymptomatic, with sustained lipid normalization and no recurrence of pancreatitis. Conclusions: This case underscores the therapeutic value of combining pharmacologic and dietary strategies in pediatric SHTG. Evidence from pediatric and adult studies supports the role of insulin infusion for acute triglyceride lowering and MCT-based nutritional therapy for long-term control. Our findings highlight the need for early, individualized, and multidisciplinary management and emphasize the potential future role of emerging targeted therapies in addressing refractory pediatric hypertriglyceridemia. Full article

Emotional dysregulation (ED) reflects a heightened reactivity to stimuli, characterized by excessive negative affect and impulsive behaviors. This study aimed to evaluate ED in workers seeking care for occupational stress and to examine its associations with sociodemographic characteristics, occupational stress, and the severity of anxiety and depressive symptoms. Eighty-seven workers referred for work-related stress were assessed using the Psychological Stress Measure (PSM) and the Job Content Questionnaire (JCQ) for stress, the Beck Depression Inventory-II (BDI-II) and the Self-Rating Anxiety Scale (SAS) for psychopathology, and the RIPoSt-40 for ED. Group comparisons and correlation analyses were conducted using parametric or non-parametric tests, as appropriate. Forty-six percent of participants met criteria for Adjustment Disorders and 54% for Major Depressive Disorder. No significant differences between diagnostic groups emerged for ED or symptom severity. Women reported higher perceived stress and anxiety than men. Negative ED domains—affective instability, negative emotionality, and emotional impulsivity—showed moderate-to-strong positive correlations with stress, anxiety, and depressive symptoms. Affective instability was also related to job stress dimensions, correlating negatively with decision latitude and positively with job demands. Negative emotional dysregulation appears to be a transdiagnostic vulnerability factor for stress-related psychopathology. Screening for ED may support early detection and targeted preventive interventions in occupational settings. Full article

Background: Maternal mortality in Brazil remains a critical indicator of social and racial inequalities, reflecting structural failures in access to and quality of obstetric care. Black women, particularly those categorized as black or brown, are at a higher risk of dying during pregnancy, childbirth, or the postpartum period. This is the result of the intersection of institutional racism, poverty, and social vulnerabilities. This study aimed to analyze trends and associated factors of maternal mortality among black women in Brazil from 2000 to 2020. Methods: This is a retrospective cohort analytical study using data from the Brazilian Mortality Information System. The sample included women aged 10 to 49 years whose underlying cause of death was classified under ICD-10 codes O00–O99. Descriptive and bivariate analyses were conducted, as well as Poisson and multinomial logistic regressions to estimate adjusted risk ratios according to skin color, education, region, type, and place of death. Results: A total of 40,907 maternal deaths were identified, with 59.2% occurring among black women. The maternal mortality ratio was 39% higher among black women compared to white women and more than double among Indigenous women. Low education, residence in the North and Northeast regions, deaths outside hospital settings, and lack of formal investigation were independently associated with increased risk. Direct obstetric causes accounted for most deaths, with hypertensive disorders and puerperal complications being the leading conditions. Conclusions: Maternal mortality among black women in Brazil reveals deep structural inequalities. Urgent public policies that incorporate an intersectional perspective, addressing race, gender, and class, are necessary to reduce disparities and ensure equitable and dignified maternal healthcare. Full article

Background and Objectives: Obesity, heart failure (HF), and atherosclerosis have common pathways, including chronic inflammation, immune cells activation, and metabolic disturbances. These pathways often coexist and overlap, increasing cardiometabolic risk. Growth differentiation factor 15 (GDF-15) is an emerging cytokine linked to inflammation, oxidative stress, and metabolic dysregulation, which are common pathways between heart failure, obesity and atherosclerosis. Beyond its established prognostic value in cardiovascular diseases (CVD) and HF, recent evidence suggests that GDF-15 may also reflect subclinical atherosclerosis, potentially improving early risk stratification in obese and HF populations. The aim of this review is to synthesize current evidence on the association between GDF-15 and markers of subclinical atherosclerosis, and to evaluate whether GDF-15 may serve as an integrative biomarker reflecting shared cardiometabolic pathways. Materials and Methods: We conducted a systematic review following PRISMA recommendations registered by CRD420251267457 number on PROSPERO. PubMed, Embase, Scopus, and Web of Science were searched for human studies evaluating the correlation between markers of subclinical atherosclerosis and GDF-15 concentration. We excluded the studies not published in English, not involving human participants, and not meeting the inclusion criteria. We assessed the risk of bias using the Joanna Briggs Institute appraisal tool. Due to the heterogeneity of studies, a narrative synthesis was performed. Result: The review included 18 studies, which evaluated the association between GDF-15 and subclinical atherosclerosis markers, such as intima media thickness, coronary artery calcium score, ankle-brachial index, and atherosclerotic plaques. Studies included patients with metabolic disorders, chronic inflammatory diseases, HIV cohorts, and general population samples. Most of the studies reported that GDF-15 levels were associated with greater atherosclerotic burden; however, results were frequently influenced by confounders. Methodological limitations, such as limited or highly specified samples, cross-sectional designs, variability in atherosclerotic-imaging technique, and inconsistent adjustment for confounders, restrict generalization of the results. Conclusions: Current evidence supports GDF-15 as a biomarker integrating inflammatory and metabolic stress signals, indirectly linking obesity, HF and subclinical atherosclerosis. While current data supports its prognostic relevance, further studies are needed to confirm its clinical utility in routine assessment and preventive cardiovascular care. Full article

Background/Objectives: Hypertensive disorders of pregnancy (HDP) remain a significant cause of maternal and perinatal morbidity worldwide. In some healthcare settings, access to angiogenic testing is limited, underscoring the need for affordable biomarkers to guide risk assessment. NT-proBNP, a marker of myocardial wall stress and cardio-renal dysfunction, may offer complementary prognostic value to the angiogenic sFlt-1/PlGF ratio. Methods: In this prospective multicenter observational study, we enrolled 180 pregnant women and categorized them into preeclampsia (PE, n = 95), non-PE HDP (gestational or chronic hypertension, n = 25), and healthy controls (n = 60). NT-proBNP and sFlt-1/PlGF levels were measured at enrollment, after 20 weeks of gestation, predominantly during the second and third trimesters. Associations with proteinuria, uric acid, creatinine, and maternal–fetal complications were examined using multivariable logistic regression adjusted for maternal age, BMI, and gestational age. Discrimination was assessed using receiver operating characteristic (ROC) curve analysis, and the incremental value of NT-proBNP beyond the sFlt-1/PlGF ratio was evaluated using ΔAUC and net reclassification improvement (NRI). Results: Median NT-proBNP levels were significantly higher in PE compared with non-PE HDP and controls (p < 0.01). NT-proBNP ≥200 pg/mL independently predicted maternal–fetal complications (adjusted OR 3.12, 95% CI 1.41–6.90, p = 0.005) and correlated with proteinuria (r = 0.47), creatinine (r = 0.43), and uric acid (r = 0.40) (all p < 0.001). sFlt-1/PlGF alone yielded an AUC of 0.84 (95% CI 0.77–0.89), while NT-proBNP alone demonstrated an AUC of 0.78 (0.71–0.84). Combining both biomarkers improved discrimination (AUC 0.88, 95% CI 0.82–0.92), with a ΔAUC of 0.04 (p = 0.02) and a continuous NRI of 0.21 (p = 0.03). The 200 pg/mL threshold for NT-proBNP achieved 80% sensitivity and 71% specificity (p < 0.001). Conclusions: NT-proBNP provides independent and complementary prognostic value to the sFlt-1/PlGF ratio in predicting maternal–fetal complications in HDP. A practical threshold of 200 pg/mL aids risk assessment, and integrating NT-proBNP into angiogenic models improves prediction. Further multicenter studies are needed to validate multimarker strategies and their cost-effectiveness. Full article

Crime in Seattle, WA (USA), has long been concentrated in a few discrete geographic areas. This study examines the impact of a one-year place-based soft policing intervention to reduce crime and disorder in these two acutely affected areas: The Blade and Little Saigon. Employing Bayesian Structural Time Series (BSTS) to estimate the treatment effect of the intervention on several crimes and calls for service measures, we find mixed results with important implications. One area responded with significant reductions in crime and community-driven calls for service. The second treatment area did not reflect these effects, suggesting that key contextual variations may influence performance of Problem-Oriented Policing treatments. Additionally, treatment effects in the first location were observed to partially diminish over time, indicating a point of diminishing returns. This study suggests that a multi-partner soft policing approach to crime reduction is effective; however, treatment must be tailored to local context, and treatment areas should be expected to adjust, necessitating programed variability to maintain treatment efficacy. A “test-as-you-go” approach is critical to optimal performance. Implications for future place-based interventions are discussed. Full article

Water deprivation triggers coordinated physiological responses to preserve body fluid balance, yet the molecular mechanisms that regulate aquaporin-mediated water transport under dehydration remain incompletely understood. Aquaporin-4 (AQP4), the main water channel in the brain and a basolateral water pathway in the kidney collecting duct, exists in multiple isoforms, including the translational readthrough variant AQP4ex, whose regulatory role is only beginning to be defined. Here, we investigated the effects of acute water deprivation (6–12 h) on AQP4 isoform expression and phosphorylation in a mouse kidney and brain. While total AQP4 and AQP4ex protein levels remained largely unchanged in both tissues, dehydration induced a marked and divergent regulation of the phosphorylated form of AQP4ex. Levels increased in the kidney medulla, consistent with enhanced antidiuretic water transport, but decreased in the cerebral cortex, suggesting a protective reduction in perivascular water permeability. No changes were detected in the cerebellum. These findings identify phosphorylation of AQP4ex as a rapid, tissue-specific regulatory mechanism that adjusts water flux according to the physiological needs of each organ, revealing an additional layer of control in systemic water homeostasis and highlighting AQP4ex as a potential target in dehydration-related and osmotic disorders. Future studies could explore the signaling pathways regulating AQP4ex phosphorylation and investigate its potential involvement in pathological conditions, such as diabetes insipidus or cerebral edema. Full article

Background/Objectives: Type 2 diabetes (T2D), a chronic metabolic disorder characterized by systemic inflammation, disproportionately affects African American adolescents. Metformin may reduce inflammation beyond glycemic control; however, its impact on inflammatory markers in adolescents remains unclear. We hypothesized that inflammatory markers would differ across groups defined by diabetes, obesity, and metformin use. Methods: In this cross-sectional analysis, inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]), metabolic panels, and metformin exposure were assessed in African American adolescents from Children’s of Alabama. Simple and multivariate linear regression models were used to test associations between metformin use and inflammatory markers, adjusting for age, sex, and BMI z-score. Results: Among 78 adolescents, metformin use was reported in 73.6% of those with T2D + obesity and 27.3% of those with obesity-only. In the T2D + obesity group, metformin use was associated with TNF-α (β = 0.34, p = 0.02). Conclusions: Metformin use was associated with higher levels of specific inflammatory markers, potentially reflecting that metformin was more likely utilized in more severe diseases. Longitudinal studies are needed to disentangle treatment effects from underlying disease progression. Full article

Background/Objectives: Patients with acute severe neurological disorders often receive a transurethral indwelling catheter (TUIC) during their initial treatment. These TUICs often remain in place until the transfer to a rehabilitation or a long-term care facility. There are no systematic concepts for bladder management and no data regarding the impact on the catheter associated, health-related quality of life (HRQoL) in this patient group. The aim of this study was to investigate the impact of successful TUIC removal on the HRQoL of those affected and to contribute to the development of systematic bladder management. Methods: A prospective longitudinal study was conducted on 33 patients treated at a neurological rehabilitation centre due to acute severe neurological disorders. The HRQoL was assessed using the SF-36 Health Survey prior to and following the TUIC removal. The influence of urinary incontinence was analysed. The mean differences were determined using a one-sample t-test adjusted for age and gender. Results: TUIC removal was successful in 61.8% (21/33). The SF-36 Health Survey showed the following improvements (adj. mean diff., 95% CI, p-value): Mental Component Summary measure (4.36, 0.34; 8.38, p = 0.035), Role-Emotional (20.89, 0.54; 41.24, p = 0.045), Physical Functioning (10.03, 3.18; 16.88, p = 0.007). The comparison between incontinent and continent patients showed a poorer HRQoL for the incontinent group. Conclusions: Successful TUIC removal has a positive influence on psychological/emotional aspects and physical functioning. Structured bladder management that considers the physical and psychological aspects of patients and nursing staff, as well as medical and economic aspects, should be pursued with vigour. Full article