Plant species with strong antioxidant activity used in traditional medicine of B&H-Sambucus nigra, Filipendula vulgaris, Helichrysum italicum, Epilobium angustifolium, Crataegus rhipidophylla, Thymus serpyllum, Vaccinium myrtillus, Symphytum officinale, Corylus avellana, and Rubus fruticosus-were analysed for their phenolic profiles and cholinesterase inhibitory activity. The HPLC-DAD analysis revealed the highest concentration of phenolic acids in S. officinale extract. Catechin, rutin, and quercetin were identified in the majority of extracts. Rutin was most abundant, especially in S. nigra flowers (9.39 mg/g DW). AChE and BChE inhibition was determined spectrophotometrically. All extracts showed activity, with AChE IC50 ranging from 0.08 mg/mL (V. myrtillus) to 8.31 mg/mL (H. italicum), and BChE from 5.35 mg/mL (T. serpyllum) to 13.26 mg/mL (C. rhipidophylla). These findings highlight the neuroprotective potential of B&H medicinal plants, with molecular docking showing phenolics like rosmarinic acid and rutin inhibit cholinesterases. Merging traditional medicinal knowledge and molecular insights offers a novel path for discovery.

This study investigated the potential of Thymus serpyllum L. and Mentha × piperita L. essential oils (EOs), known for their bioactive properties, as adjunctive treatments targeting Basal cell carcinoma cancer stem cells (BCC CSCs). Primary cultures were established from ten BCC tumor samples and their distant resection margins as controls. The chemical composition of the EOs was analyzed by gas chromatography–mass spectroscopy (GC-MS) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The biological effects were evaluated via colony and spheroid formation, scratch assays, MTT and neutral red cytotoxicity assays, and qRT-PCR for Hh (SHH, PTCH1, SMO, and GLI1) and Notch (Notch1 and JAG1) gene expression. GC analysis identified thymol, p-cymene, and linalool as the main components of the EO of T. serpyllum L., and menthone and menthol in the EO of M. × piperita L. IC50 values were 262 µg/mL for T. serpyllum L. and 556 µg/mL for M. × piperita L. and were applied in all experiments. Both EOs significantly reduced CSC clonogenicity and migration (p < 0.05). The EO of T. serpyllum L. downregulated SMO and GLI1, while the EO of M. × piperita L. upregulated PTCH1, Notch1, and JAG1 (p < 0.05). These findings suggest that both EOs exhibit anticancer effects in BCC CSCs by modulating key oncogenic pathways, supporting their potential in BCC therapy.

Aim To systematically review the efficacy and safety of fixed-dose combination (FDC) antihypertensive agents in chronic kidney disease (CKD). Methods This systematic review included studies from January 2014 to December 2023 that evaluated FDC antihypertensives in CKD. We searched The PubMed, Embase, and the Cochrane Library databases were searched. Inclusion criteria encompassed studies written in English and published in peer-reviewed journals. Exclusion criterias among others were review articles, editorials, letters, and conference abstracts. Results Six studies met inclusion criteria from 1156 identified publications. Analyzed studies were  included randomized trials (4), cohort studies (1), and retrospective analyses (1). FDCs improved medication adherence, blood pressure control, and renal outcomes. Significant blood pressure  puni naziv skraćenice (BP) reductions were noted with FDCs compared with free combinations. FDCs of renin-angiotensin system inhibitors and thiazide diuretics showed improved adherence, reduced major adverse cardiovascular events, and better renal function preservation. Some combinations losartan hidrochlortiazid demonstrated a more significant reduction of proteinuria and urinary protein-to-creatinine ratio (UPCR), indicating potential renoprotective effects. Conclusion While using FDC antihypertensives has shown promising results in improving patient outcomes in CKD, further large-scale, long-term randomized trials are urgently needed to confirm these findings and optimize treatment strategies. Keywords:  cardiovascular diseases, hypertension management, medication adherence, proteinuria, renoprotection  .

Previous studies have demonstrated the feasibility of estimating the speech reception threshold (SRT) based on electroencephalography (EEG), termed SRTneuro, in younger normal-hearing (YNH) participants. This method may support speech perception in hearing-aid users through continuous adaptation of noise-reduction algorithms. The prevalence of hearing impairment and thereby hearing-aid use increases with age. The SRTneuro estimation is based on envelope reconstruction accuracy, which has also been shown to increase with age, possibly due to excitatory/inhibitory imbalance or recruitment of additional cortical regions. This could affect the estimated SRTneuro. This study investigated the age-related changes in the temporal response function (TRF) and the feasibility of SRTneuro estimation across age. Twenty YNH and 22 older normal-hearing (ONH) participants listened to audiobook excerpts at various signal-to-noise ratios (SNRs) while EEG was recorded using 66 scalp electrodes and 12 in-ear-EEG electrodes. A linear decoder reconstructed the speech envelope, and the Pearson's correlation was calculated between the reconstructed and speech-stimulus envelopes. A sigmoid function was fitted to the reconstruction-accuracy-versus-SNR data points, and the midpoint was used as the estimated SRTneuro. The results show that the SRTneuro can be estimated with similar precision in both age groups, whether using all scalp electrodes or only those in and around the ear. This consistency across age groups was observed despite physiological differences, with the ONH participants showing higher reconstruction accuracies and greater TRF amplitudes. Overall, these findings demonstrate the robustness of the SRTneuro method in older individuals and highlight its potential for applications in age-related hearing loss and hearing-aid technology.

This study aims to investigate individual and joint effects of digitalization and inbound open innovation (OI) on technological (product and process) innovations in German firms. In particular, two specific forms of digitalization are considered – artificial intelligence (AI) and big data analytics (BDA), as well as the search breadth as a measure of inbound OI. To answer this research question, an econometric analysis is conducted on a sample of Germany firms using the Mannheim Innovation Panel dataset from the wave conducted in 2019 and covering the period 2016–2018. Moreover, the study reports results for the manufacturing and service sectors separately. This sectoral analysis sheds light on any potential differences in the innovation effects of digitalization and OI practices. Our empirical findings are heterogeneous and show that, overall, AI positively impacts product innovation, while BDA increases the likelihood of process innovation. Moreover, AI and the breadth of knowledge search do not yield synergistic innovation effects, while BDA weakens the positive impact of search breadth on process innovation. Based on empirical findings, we discuss theoretical, managerial and policy implications. This study contributes to the literature by examining the influence of digitalization and inbound OI on technological, product and process innovations. In addition, this study examines the mediating effect that digitalization and inbound OI can exert on technological innovation in German firms. The full sample is divided into manufacturing and service sectors to disentangle potentially heterogeneous effects of inbound OI and digitalization on innovation performance.

In this pilot study, a subset of CALERIE Phase 2 (No. NCT00427193, registered 25th Jan 2007) participants (n = 26) were evaluated for the effects of 2 years of 25% calorie restriction (CR) on N-glycosylation of IgG, plasma, and complement C3, as well as IgG-based biological age (GlycAge). Plasma samples were collected at baseline (BL), 12 (12mo), and 24 months (24mo). IgG galactosylation was higher at 24mo compared to BL (p = 0.051) and increased from 12mo to 24mo (p = 0.016); GlycAge decreased over the same period (p = 0.027). GlycAge was positively associated with TNF-α (p = 0.030) and ICAM-1 (p = 0.017). Between BL and 24mo, plasma high-branched glycans declined (p = 0.013), bisecting GlcNAcs increased in both plasma (p < 0.001) and IgG (p = 0.01), complement C3 protein (p < 0.001), C3-Man9 (p < 0.001), and C3-Man9Glc1C3 (p = 0.046) were reduced. The absence of a control group warrants cautious interpretation.

Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the vesicular rash is a hallmark sign, it is absent in approximately 5% of cases. Visceral involvement may precede cutaneous lesions, complicate early recognition, and increase the risk of severe complications. This scoping review screened 594 articles of which 153 met the inclusion criteria, yielding 156 individual cases. Patients were predominantly male (53.8%), with a mean age of 42.3 years. The overall mortality rate was 25.0%. Multiple organs were involved in 46.1% of cases. The most frequently affected were the lungs (56%), liver (44%), heart (16%), kidneys (11%), pancreas (11%), stomach (10%), and esophagus (6%). Antivirals were administered in 89.1% of cases, while corticosteroids were used in 22.4%, with no significant impact on outcomes. Early diagnosis, achieved in 65.4% of patients, was significantly associated with survival (p = 0.043). Mortality was significantly associated with underlying comorbidities (p = 0.004), especially autoimmune diseases requiring immunosuppression (p = 0.048). Septic shock or multi-organ dysfunction (MODS), hepatitis, acute kidney injury, and acute liver failure were linked to higher mortality in univariate analysis. Multivariate analysis identified comorbidities (p < 0.001), septic shock/MODS (p = 0.008), and acute liver failure (p = 0.039) as independent predictors of mortality. Patients with septic shock/MODS had over twice the risk of death (OR = 2.24; p = 0.008). This review underscores the diagnostic challenges and high mortality of VD-VZV. Early recognition and timely administration of antiviral treatment appear critical for survival. Greater clinical awareness and further research are needed to guide management.

Biomaterials, both natural and synthetic, play a crucial role in medical applications by interacting with biological systems to treat or replace tissues. These materials must exhibit biocompatibility to avoid complications like immunological rejection and be degradable to ensure proper breakdown within the body after fulfilling their intended function. Common natural biomaterials include collagen, gelatin, and alginates, while synthetic materials such as polyurethane, fibronectin, and ceramics are also widely used. Over the past decade, there has been significant progress in the field of biomaterials, driven by advances in regenerative medicine and tissue engineering. These materials are now frequently used in a variety of clinical applications, from tissue healing and molecular probes to nanoparticle biosensors and drug delivery systems. Despite the progress, understanding how biomaterials interact, integrate, and function in complex biological environments remains a significant challenge. The ability of biomaterials to restore and enhance biological functions, particularly in areas such as tissue engineering, orthopedic surgery, and neural implants, has demonstrated substantial improvements in patient outcomes and quality of life. Key to their success in these applications are their biocompatibility, long-term stability, and effective integration with host tissues. This paper explores the evolving role of biomaterials in medical practice, evaluating their potential, current use, and ongoing challenges in clinical settings, with a focus on their contributions to healthcare advancements and patient care.

Fatty-acid-hydroxylase-associated neurodegeneration (FAHN) is a rare neurodegenerative disorder caused by loss-of-function mutations in the FA2H gene, leading to impaired enzymatic activity and resulting in myelin sheath instability, demyelination, and axonal degeneration. In this study, we established a human in vitro model using neurons and oligodendrocytes derived from induced pluripotent stem cells (hiPSCs) of a FAHN patient. This coculture system enabled the investigation of myelination processes and myelin integrity in a disease-relevant context. Analyses using immunofluorescence and Western blot revealed impaired expression and localisation of key myelin proteins in oligodendrocytes and cocultures. FA2H-deficient cells showed reduced myelination, shortened internodes, and disrupted formation of the nodes of Ranvier. Additionally, we identified autophagy defects—a hallmark of many neurodegenerative diseases—including reduced p62 expression, elevated LC3B levels, and impaired fusion of autophagosomes with lysosomes. This study presents a robust hiPSC-based model to study FAHN, offering new insights into the molecular pathology of the disease. Our findings suggest that FA2H mutations compromise both the structural integrity of myelin and the efficiency of the autophagic machinery, highlighting potential targets for future therapeutic interventions.

Introduction: Non-ST elevation myocardial infarction (NSTEMI) carries a substantial risk of early major adverse cardiovascular events (MACE) despite advances in therapy. Easily obtainable biochemical and echocardiographic markers may improve early risk stratification, particularly in patients managed without revascularization. This prospective study assessed the prognostic significance of inferior vena cava (IVC) diameter, serum uric acid, homocysteine, and selected hematological indices in predicting 90-day MACE in NSTEMI patients treated with conservative medical therapy. Unlike prior studies that examined these biomarkers individually, our study integrates biochemical (uric acid, homocysteine), echocardiographic (IVC diameter), and hemogram-derived indices into a combined model for early risk stratification in conservatively treated NSTEMI patients. Methods: A total of 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023 were included. All patients received guideline-directed medical therapy. Clinical, echocardiographic, and laboratory data were obtained within 24 hours of admission. The primary endpoint was MACE (cardiac death, reinfarction, or urgent coronary revascularization) within 90 days. Logistic regression identified independent predictors; discriminatory ability was assessed using receiver operating characteristic (ROC) analysis, and Kaplan-Meier curves evaluated event-free survival. Results: MACE occurred in 87 patients (51.2%). Compared to event-free patients, those with MACE had larger IVC diameters (20.25 ± 2.52 mm vs. 18.36 ± 2.16 mm; p < 0.001), higher uric acid (432.8 ± 47.3 μmol/L vs. 358.9 ± 44.6 μmol/L; p < 0.001), and elevated homocysteine levels (18.42 ± 4.13 μmol/L vs. 13.39 ± 2.88 μmol/L; p < 0.001). In multivariate analysis, uric acid (OR per 10 μmol/L = 1.32; 95% CI: 1.05-1.65; p = 0.015) and homocysteine (OR per 1 μmol/L = 1.23; 95% CI: 1.06-1.42; p = 0.005) remained independent predictors. ROC analysis showed excellent discrimination for homocysteine (AUC: 0.844) and uric acid (AUC: 0.830). IVC diameter was associated with lower MACE-free survival (log-rank p = 0.036) but lost significance after adjustment. Conclusion: Elevated homocysteine and uric acid independently predicted 90-day MACE in NSTEMI patients managed without revascularization. While IVC diameter was not independently predictive, its combination with biochemical markers may enhance risk stratification and guide early post-discharge management. These findings warrant validation in larger multicenter studies.

Background/Objectives: This study aimed to evaluate the diagnostic and prognostic utility of B7-H3 expression in differentiating low-grade gliomas (LGGs) from high-grade gliomas (HGGs) and to examine its association with clinical outcomes. Methods: This retrospective study included 99 patients with histopathologically confirmed gliomas (42 LGGs and 57 HGGs). B7-H3 expression was assessed using immunohistochemistry and scored by immunoreactive score (IRS). Results: B7-H3 expression was significantly higher in HGG compared to LGG (p < 0.001). The total IRS (B7-H3 A × B) demonstrated strong discriminative power (AUC = 0.816). High B7-H3 expression independently predicted disease progression (OR = 4.9, 95% CI: 2.4–10.1; p < 0.001) and was associated with IDH wild-type status and elevated Ki-67 index. Patients with high B7-H3 had significantly shorter overall survival (median 6 months vs. 42 months) and progression-free survival (median 3 months vs. 25 months) (both p < 0.001). Cox regression confirmed high B7-H3 as an independent predictor of mortality (HR = 2.9, 95% CI: 1.7–4.7; p < 0.001) and progression (HR = 2.6, 95% CI: 1.6–4.2; p < 0.001). Conclusions: B7-H3 expression is a reliable biomarker for distinguishing HGG from LGG and is independently associated with worse survival outcomes. Its assessment may aid in glioma classification and prognostication.