Search Results (14,638)

Background/Objectives: High blood pressure remains a primary modifiable risk factor for cardiovascular disease. Nicotinamide mononucleotide (NMN) has emerged as a promising supplement; however, its efficacy with respect to blood pressure in humans is unclear. This meta-analysis systematically evaluated the effects of various NMN supplements on resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with elevated blood pressure. Methods: A systematic literature search was conducted to identify eligible randomized controlled trials (RCTs) using the databases PubMed/MEDLINE, Scopus, Web of Science, and EBSCO from their inception to 13 December 2025. R software was used to combine the data from the included original trials using a common-effects model. Subgroup analyses were performed based on age, baseline body mass index, geographical location, intervention duration, NMN dosage, and baseline blood pressure. Results: A total of 349 participants from 10 RCTs with 11 intervention arms were included. Compared with the placebo, NMN supplementation was associated with a statistically significant but modest reduction in resting DBP (WMD, −2.15 mmHg; 95% CI: −3.68 to −0.61). In contrast, the reduction in resting SBP was not statistically significant. Notably, subgroup analyses revealed that NMN supplementation resulted in a significant reduction in SBP specifically among participants aged 60 years and older (WMD: −3.94 mmHg; 95% CI: −7.06 to −0.82). Conclusions: Our findings provide preliminary and suggestive evidence that NMN supplementation may be associated with a small reduction in resting DBP and a modest beneficial effect on resting SBP in adults aged 60 years and older. However, the potential of NMN as a viable candidate for early-stage blood pressure management requires confirmation through long-term, large-scale, high-quality RCTs in future clinical studies. Full article

Medulloblastoma is the most common malignant brain tumor in children, but it presents distinct challenges when occurring in adolescents and young adults (AYAs, aged 15–39 years). Recent molecular profiling has identified four principal medulloblastoma subgroups—WNT-activated, SHH-activated, Group 3, and Group 4—each demonstrating unique biological characteristics and clinical outcomes. AYA patients exhibit age-specific molecular patterns and therapeutic responses substantially different from those of younger children. This review synthesizes current evidence regarding epidemiology, diagnostic challenges, molecular characterization, risk stratification, treatment modalities, and outcomes specific to AYA medulloblastoma patients, highlighting the critical need for age-adapted therapeutic strategies and dedicated clinical research in this underserved population. Full article

Background/Objectives: As a treatment, fluoropyrimidines are often associated with early moderate-to-severe toxicity. Although pre-emptive DPYD genotyping enables genotype-guided dosing, significant adverse events still occur in patients classified as DPYD wild-type (WT). The aim of this study was to identify DPYD variants and evaluate the contributions of TYMS, ENOSF1, CDH4, and CDA variants to fluoropyrimidine toxicity. Methods: A total of 256 European ancestry patients (aged ≥ 18 years, had completed ≥6 cycles of chemotherapy, and were WT for the DPYD variants routinely tested for) underwent genotyping for TYMS, ENOSF1, CDH4, and CDA variants, and full DPYD exon sequencing was performed in 56 of these patients. Toxicity was defined as fluoropyrimidine-related adverse events requiring a dose reduction. Multivariable models were adjusted for sex, fluoropyrimidine type, and the Charlson Comorbidity Index, and time-to-event was assessed using the Kaplan–Meier/Cox proportional hazards models. Results: A subgroup of 117 patients experienced toxicity requiring a dose reduction. The most frequent events were asthenia, gastrointestinal toxicity, hand–foot syndrome, and haematological toxicity. The ENOSF1 rs2612091 C allele was associated with fluoropyrimidine withdrawal and a shorter time to dose reduction. In the patients treated with 5-fluorouracil, TYMS rs11280056 was associated with toxicity. DPYD exon sequencing identified thirteen variants, nine of which were more prevalent in the toxicity group. These included a canonical splice site (c.150+1G>A) and a stop-gained (c.1863G>A) variant, which is predicted to result in loss of function. Conclusions: In real-world practice, despite undergoing standard DPYD genotyping, DPYD WT patients receiving a full dose of fluoropyrimidines develop clinically relevant toxicity. The presence of rare DPYD variants and associated genes (ENOSF1 and TYMS) suggests that broader, prospectively validated pharmacogenetic strategies may improve toxicity prevention. Full article

Background: Spirulina supplementation combined with structured exercise may improve obesity-related metabolic dysfunctions. This research examined whether this combination enhances body composition, glucose levels, lipid profile, and cardiorespiratory fitness in overweight and obese adults. Methods: Following PRISMA 2020 guidelines, a systematic search of Scopus, PubMed, and Web of Science identified randomized controlled trials (RCTs) evaluating spirulina (1–6 g/day) combined with structured exercise in individuals with overweight and obesity (BMI ≥ 25). The search retrieved 91 records, of which 10 studies met the inclusion criteria and were included in the systematic review. Nine studies provided sufficient post-intervention data and were included in the quantitative meta-analysis using a random-effects model, with heterogeneity assessed using τ², Q, and I² statistics. Publication bias was evaluated using rank correlation, regression-based tests, trim-and-fill, and fail-safe N analyses. Results: Combined spirulina supplementation and structured exercise (6–12 weeks) was associated with reductions in BMI (−1.34 kg/m²), body fat percentage (−3.03%), fasting glucose (−14.47 mg/dL), LDL-C (−12.68 mg/dL), and triglycerides (−9.81 mg/dL), along with increases in VO2max (3.25 mL/kg/min) and HDL-C (4.21 mg/dL). Effect estimates were generally larger in combined exercise–spirulina subgroups, particularly in HIITsupp and R-AEsupp conditions, whereas supplementation-only comparisons demonstrated smaller and less consistent changes. Inflammatory markers and adipokines (CRP, TNF-α, MCP-1, IL-6, IL-8) showed favorable directional changes in individual trials. Conclusions: Spirulina combined with structured exercise was associated with changes in anthropometric, glycemic, cardiorespiratory, and lipid parameters in individuals with overweight or obesity. Full article

The maxillary sinus is frequently implicated in facial pain syndromes arising from infection, neoplasia, dental procedures, and, importantly, migraine, which can mimic “sinus headache” and contribute to misdiagnosis and inappropriate antibiotic use. Despite the clinical burden of chronic maxillary sinus pain, the sensory neuron subtypes that convey nociceptive and mechanosensory signals from the sinus mucosa remain incompletely defined. In this study, trigeminal ganglion (TG) neurons innervating the maxillary sinus (maxillary sinus TG neurons) were retrogradely labeled with the fluorescent dye DiD in mice and characterized using ex vivo patch-clamp electrophysiology and single-cell RT-PCR. Maxillary sinus TG neurons were found to be predominantly small-diameter, C-afferent nociceptors with electrophysiologic features including high thresholds, repetitive firing, and broad action potentials. Notably, maxillary sinus TG neurons formed a distinct molecular and functional subgroup: they expressed Nav1.9, while showing minimal Nav1.8 expression and limited overlap with Nav1.8-positive nociceptor populations. A majority of maxillary sinus TG neurons were mechanically responsive, generating mechanically activated currents with heterogeneous adaptation profiles, and a subset expressed the mechanoreceptor Piezo2. Collectively, these findings identify maxillary sinus TG neurons as a specialized population of Nav1.9-enriched C-afferent nociceptors with mechanosensitive properties, providing a mechanistic framework for pressure-evoked sinus pain. This work advances the neurobiological basis of sinus-related pain and suggests that Nav1.9 and mechanoreceptor pathways may be potential therapeutic targets for conditions in which sinus symptoms overlap with migraine and other craniofacial pain disorders. Full article

Background/Objectives: Umbilical–portal–systemic venous shunts (UPSVS) are rare fetal vascular anomalies with heterogeneous embryologic origins and variable perinatal implications. Although prenatal diagnosis has increased with advances in fetal imaging, data correlating prenatal subclassification with structural/genetic abnormalities and neonatal outcomes remain limited. Methods: This retrospective study included 50 fetuses prenatally diagnosed with UPSVS at a tertiary referral perinatology center between 2021 and 2025. Cases were subclassified according to the Achiron prenatal classification into Type 1 umbilical–systemic shunt (USS), Type 2 ductus venosus–systemic shunt (DVSS), Type 3a intrahepatic portosystemic shunt (IHPSS), and Type 3b extrahepatic portosystemic shunt (EHPSS). Prenatal ultrasound, Doppler, fetal echocardiography, and genetic testing (karyotype and chromosomal microarray) were analyzed. Perinatal metrics—including structural/genetic anomalies, fetal growth restriction (FGR), termination of pregnancy (TOP), and neonatal outcomes—were evaluated with postnatal verification. Results: The distribution of subtypes was Type 1: 28% (14/50), Type 2: 48% (24/50), Type 3a: 20% (10/50), and Type 3b: 4% (2/50). Gestational age at diagnosis was significantly higher in Type 3a compared with Type 1 and Type 2 (32.2 ± 2.4 vs. 21.1 ± 6.7 and 22.4 ± 5.8 weeks; p < 0.001). Structural anomalies were most frequent in Type 1 (13/14, 92.9%; p < 0.001), while FGR predominated in Type 3a (9/10, 90%; p = 0.006). Ductus venosus (DV) agenesis was universal in Type 1 (14/14) and Type 3b (2/2), absent in Type 2 (0/24), and present in 20% of Type 3a (2/10) (p < 0.001). Genetic abnormalities were detected in 57% of Type 1 (4/7) and 56% of Type 2 (9/16) fetuses, with trisomy 21 most prevalent in Type 2. TOP was highest in Type 1 (8/14, 57.1%; p < 0.001). Adverse neonatal outcomes occurred primarily in Type 1 and Type 3b (p < 0.001), whereas Type 2 demonstrated favorable neonatal outcomes. Conclusions: UPSVS subtype is strongly associated with structural/genetic anomalies, FGR, and neonatal outcomes, underscoring the importance of prenatal subclassification in prognostic assessment and counseling. Type 1 and Type 3b represent the highest—risk subgroups requiring delivery planning in tertiary centers, while Type 2 generally exhibits a benign perinatal course. The association between Type 3a and FGR highlights the need for detailed evaluation of the hepatic venous system in growth-restricted fetuses. However, interpretation of subgroup-specific associations should consider the relatively small sample size of Type 3b cases and the limited genetic testing performed in some Type 3a fetuses. Multicenter prospective studies are warranted to standardize diagnostic algorithms, optimize genetic testing strategies, and refine perinatal management. Full article

Background: Major cervical burns often require tracheostomy (TT); however, it remains unclear whether TT timing relative to cervical wound coverage (WC) and the choice of coverage modality affect peristomal wound healing. Methods: In this retrospective single-center cohort study, we included 48 adults with thermally induced cervical burns who underwent TT between 2015 and 2024 in a specialized burn ICU. Eleven patients died before decannulation and were excluded from the primary endpoint analysis. Cervical wound-healing disturbance (CWHD) as a primary endpoint was assessed in the remaining 37 patients, including 13 treated with advanced cervical dressings and 24 treated with split-thickness skin grafts (STSG). Results: CWHD occurred in 2/13 (15.4%) with advanced dressings and 11/24 (45.8%) after STSG. Within the grafted subgroup, complication rates did not differ significantly according to TT sequencing relative to WC, TT–WC interval, grafting technique (mesh vs. Meek), or tracheostoma closure method (all p > 0.05). In multivariable logistic regression, only cervical burn depth independently predicted CWHD. Conclusion: In patients with cervical burns requiring TT, burn depth/severity, rather than TT timing, grafting strategy, or closure technique, appears to drive peristomal wound complications, supporting individualized planning instead of rigid algorithms. Full article

Scientific evidence supports the role of the autotaxin-lysophosphatidic acid (ATX-LPA) pathway in obesity and liver damage. The present study aim is to investigate variations in serum ATX and LPA levels across different BMI categories in a subcohort of subjects with MASLD. The study sample comprises 199 patients with liver steatosis from the most recent follow-up of the MICOL study, a prospective cohort study established in 1985, based on a random sample of the population of Castellana Grotte. In adjusted model, a positive association of BMI with ATX was observed when modeled as both a continuous (β = 0.018, p < 0.001, 0.012 to 0.024 95% C.I.) and categorical variable β = 0.170, p < 0.001, 0.111 to 0.228 95% C.I.). Conversely, a negative association was observed for LPA alone (β = −0.083, p = 0.020, −0.152 to −0.013 95% C.I.) and for the BMI and LPA interaction term (β = −0.109, p = 0.002, −0.176 to −0.042 95% C.I.). A positive association between ATX levels and BMI was found, whereas LPA levels tended to decrease with increasing BMI. Within the obese subgroup, ATX concentrations were notably higher in female compared to male participants. These findings suggest that elevated ATX in MASLD may reflect obesity-related metabolic and inflammatory alterations rather than adiposity alone, possibly involving altered LPA feedback and metabolism. Full article

Introduction: Breast reconstruction and breast augmentation via silicone breast implants are among the most commonly performed implant surgeries worldwide. However, these surgeries entail notable risks for postoperative implant complications, including implant rupture or capsular contracture. This study investigates the significance of microbial contamination regarding the development of peri-implant inflammation and its impact on implant-related complications. Methods: A total of 125 breast implant revisions in 97 patients with a history of breast cancer or prior cosmetic breast augmentation were analyzed at the Clinical Department of Plastic, Aesthetic, and Reconstructive Surgery, University Clinic of St. Poelten, between February 2021 and August 2023. Microbial contamination and subclinical inflammation were assessed using histological and microbiological analysis of implant surfaces and capsules. The implants were grouped by their initial indication for surgery, along with presence of contamination, inflammation, and complications, and then compared using a Chi² test, Fisher’s exact test and two-sided t-tests. Results: Microbial contamination was found in 27 implants (21.6%), and 58 implants (48.74%) showed histological evidence of inflammation. Peri-implant inflammation was significantly more often observed in contaminated implants (p = 0.049). Implants displaying histological signs of peri-implant inflammation showed significantly higher rates of complications, particularly implant rupture (p < 0.001 each). In a subgroup analysis, cosmetic patients presented a significantly higher rate of peri-implant inflammation compared to breast cancer patients (p < 0.001). Cosmetic patients also showed significantly longer implant inlay times compared to breast cancer patients (14.32 vs. 3.76 years, p < 0.001), suggesting that prolonged implant inlay duration may contribute to the occurrence of peri-implant inflammation. Conclusion: Subclinical microbial contamination appears to accelerate the inflammatory reactions to silicone implants that subsequently increase the risk for complications and thus surgical removal. Additionally, prolonged implant inlay time seems to be a major independent contributor to chronic, low-grade inflammation, even in the absence of microbial contamination. Full article

Background and Objectives: Increased axial length is a major risk factor for retinal detachment. This study explored whether, in individuals presenting with unilateral disease, the longer eye was more likely to have rhegmatogenous disease. Materials and Methods: A consecutive cohort of 276 patients (100 female; mean age 62 ± 10 years), presenting with PVD-related retinal detachment or retinal tear between 2018 and 2024 in South Australia, had their axial length measured by partial coherence interferometry. Two-sample and paired t-tests were used to compare the affected and fellow eyes. Results: There was no significant difference in the axial length between the retinal detachment eyes and fellow eyes overall (n = 181; mean AL 24.93 vs. 24.82 mm; p = 0.41), or when considering a paired analysis of those with bilateral data (n = 139, 24.69 vs. 24.71 mm; p = 0.92), with the affected eye longer in 71/139 cases. Similar results were observed for retinal tear cases (n = 80; p = 0.20) and for the entire cohort with bilateral data (n = 219, p = 0.50). Sub-group analyses by axial length asymmetry (>0.1–1.0 mm, p = 0.63–0.97) and considering only larger eyes also found no significant difference (p = 0.38–0.98). Conclusions: Within individuals, the longer eye is not more likely to present with retinal detachment or retinal tear. This suggests that axial length is associated with, but not causative of, rhegmatogenous disease within individuals. Full article

Foot orienteering is an endurance sport that requires high musculoskeletal efficiency to maintain performance while running across varied and uneven terrain. This study aimed to assess functional movement competency in national-level foot orienteers (FO) using the Functional Movement Screen™ (FMS™). Fifty-one athletes (21 females and 30 males) from Spain, Italy, and Poland were evaluated to analyze fundamental movement patterns. Participants were grouped according to sex, age category (junior vs. senior), and body mass index (BMI). The median FMS™ score for the entire cohort was 17.0, with no significant differences observed between males and females, juniors and seniors, or BMI categories. Junior female athletes achieved significantly higher scores than junior males in the Hurdle Step test (r = 0.37, p = 0.048), and a positive correlation was identified between age and Hurdle Step performance (r = 0.319, p = 0.02), indicating lower scores in younger athletes. Athletes with lower BMI demonstrated superior performance in the Shoulder Mobility test (r = 0.38, p = 0.01), supported by a moderate negative correlation between BMI and shoulder mobility (r = −0.37, p = 0.01). Across all subgroups, the lowest scores were recorded in the Deep Squat test. These findings suggest that age, sex, and BMI may influence specific components of functional movement competency in FO and should be considered when designing training and injury-prevention programs. Further research involving national teams from additional countries is recommended to confirm and extend these results. Full article

Background: This proof-of-concept study examined the association between CT-derived sarcopenia indices and achievement of Patient Acceptable Symptom State (PASS) in a metabolically homogeneous subgroup of patients with psoriatic arthritis (PsA) receiving biologic therapy. Methods: We retrospectively analyzed 26 PsA patients without diabetes, hypertension, or thyroid disorders who were treated with TNF or IL-17 inhibitors and underwent opportunistic CT imaging at the L2 vertebral level. Body composition parameters included total abdominal muscle area (TAMA), subcutaneous adipose tissue (SAT), and sarcopenia index (SI = TAMA/height²). PASS achievement at 12 weeks was assessed retrospectively. Receiver operating characteristic (ROC) analysis was performed. Results: Fourteen patients achieved PASS. Compared with non-achievers, these patients had significantly higher TAMA, SAT, and SI values (all p < 0.05). ROC analysis identified an SI threshold of 4657.5 cm²/m² (sensitivity 78.6%, specificity 83.3%, p = 0.003). Conclusions: In this metabolically homogeneous PsA subgroup, higher CT-derived muscle mass measures were associated with PASS achievement at 12 weeks. These findings are hypothesis-generating and require validation in larger prospective cohorts. Full article

Background: The ISCHEMIA trial demonstrated no overall prognostic benefit of an initial invasive strategy over optimal medical therapy (OMT) in patients with chronic coronary syndrome (CCS) and moderate-to-severe ischemia. However, managing patients with stable angina and low systolic blood pressure (SBP) remains challenging due to limited tolerance to vasodilatory anti-anginal drugs and the uncertain role of revascularization in improving long-term outcomes for this subgroup. Objectives: This study aimed to estimate the treatment effect of an initial invasive strategy (INV) compared with conservative medical therapy (CON) on long-term clinical outcomes and quality of life in patients with stable angina, particularly those with low baseline systolic blood pressure (≤120 mmHg). Methods: We conducted a post hoc analysis of 3544 patients with stable angina from the ISCHEMIA trial, divided into an initial invasive strategy or a conservative approach. The primary endpoint was a 3-year composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina or heart failure, or resuscitated cardiac arrest. Health-related quality of life was assessed using the Seattle Angina Questionnaire (SAQ). In the subgroup, patients were stratified by baseline SBP, diastolic blood pressure (DBP) and heart rate; the Cox model was adjusted for the covariates. Results: Baseline characteristics were generally comparable between the two groups. Over 3 years of follow-up, no significant difference in primary endpoint events was observed between the INV and CON group in the overall cohort (HR = 0.94, 95%CI 0.77–1.14, p = 0.53), and the INV group had the higher SAQ score. Among patients with low baseline SBP (≤120 mmHg), after adjusting for clinical factors using Cox regression, randomized treatment assignment to the INV approach significantly reduced adverse cardiovascular events compared with conservative therapy (HR = 0.58, 95%CI 0.38 to 0.89). Conclusions: In patients with stable angina, an invasive strategy improved long-term quality of life. Among those with low baseline SBP (≤120 mmHg) and limited tolerance to vasodilatory anti-anginal drugs, invasive management reduced 3-year adverse events, supporting tailored revascularization strategies for these patients; a larger cohort is needed for validation. However, this subgroup-specific causal contrast derives from a post hoc exploratory analysis and should be interpreted cautiously; prospective randomized studies are needed to further validate these findings. Full article

The primary objective of this study was to evaluate the relative contributions of the MMSE and nWBV in three-class cognitive stage classification, with a secondary objective of conducting a subgroup analysis to investigate latent risk within the MMSE-normal population. To achieve this, we proposed an explainable deep-learning-based analytical framework integrating the MMSE with nWBV, a structural brain atrophy indicator, and systematically assessed the relative contributions of each variable in cognitive impairment stage classification and potential risk screening. Although the MMSE is widely used in clinical practice as a cognitive screening tool, it has limited sensitivity to early or subtle cognitive decline and may not adequately reflect structural brain changes due to the ceiling effect. To address this limitation, we compared four tabular deep learning models—MLP, Tab ResNet, Tab Transformer, and FT Transformer—under identical fivefold cross-validation conditions. Age and sex were fixed as covariates, and feature ablation analysis was conducted to examine the independent and combined effects of the MMSE and nWBV. The results showed no statistically significant differences in classification performance among model architectures, indicating that predictive performance was primarily determined by the informational content of the input variables rather than model complexity. In the feature ablation analysis, the MMSE alone demonstrated strong discriminative power, whereas nWBV alone showed relatively limited performance; however, when combined with the MMSE, nWBV consistently improved classification performance. Furthermore, for interpretability analysis, both Integrated Gradients (IG) and SHAP were applied to validate variable contributions from complementary perspectives. Across both methods, the MMSE and nWBV were repeatedly identified as key contributing features, and interpretability stability was maintained throughout cross-validation folds, supporting the robustness and reliability of the explanatory results. Beyond simple model performance comparisons, this study provides evidence supporting the complementary integration of structural brain atrophy information into MMSE-centered traditional cognitive assessment by jointly considering variable contribution and interpretability stability. This approach is expected to contribute to precision risk screening and clinical decision support in the early stages of cognitive decline. Although the MMSE exhibited strong discriminative performance, nWBV provided complementary structural risk signals within the MMSE-normal subgroup, suggesting that integrating cognitive assessment with structural biomarkers may enhance early risk identification. Full article

Background: Exercise enjoyment supports adherence, whereas elevated exercise addiction risk reflects potentially maladaptive persistence marked by rigidity and internal pressure. This study examined the association between enjoyment and exercise addiction risk in Turkish adults and explored variation across sociodemographic, lifestyle, and exercise-related characteristics. Methods: A total of 420 adults (45.0% women, 55.0% men; mean age = 25.68 years) completed an online survey including the Exercise Enjoyment Scale (EES) and the Exercise Addiction Inventory (EAI). Results: Enjoyment was weakly and inversely associated with exercise addiction risk (r = −0.18, p = 0.0002; 95% CI: −0.27 to −0.09). Women reported higher enjoyment and higher EAI scores than men. The proportion screening positive for elevated risk (EAI ≥ 24) was 13.8% (n = 58; 95% CI: 10.8–17.4%); subgroup comparisons were interpreted as exploratory (no multiplicity correction). Conclusions: Enjoyment tended to vary with participation patterns, whereas addiction risk tended to vary with training structure and motives; longitudinal studies are needed to clarify temporal ordering. Full article