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.

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.

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.

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.

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.

INTRODUCTION The rat sciatic nerve crush injury model is commonly employed to evaluate the efficacy of treatments aimed at promoting nerve regeneration. This review examines various crush techniques and the types of nerve injuries they are designed to produce. METHODS A literature review was conducted using PubMed, Embase, Web of Science, and SCOPUS for studies published between 2010 and 2024. Studies were included if they involved surgical crush injuries on the rat sciatic nerve, performed at least one sensory functional evaluation, and compared outcomes with naive or sham controls. Crush techniques and the resulting nerve injuries were analyzed based on postoperative sensory evaluations. RESULTS Of the 48 studies reviewed, 21 met the inclusion criteria. The crush techniques used included clamp (11 studies), forceps (5), clip (4), and others (1), all of which resulted in sensory impairments. Ten studies reported transient impairments with recovery to control levels, while 11 reported no recovery during the observation period (permanent). The transient group had significantly longer observation periods compared to the permanent group (57.7 vs. 17.4 days, p = 0.0009). ROC analysis determined 25 days as the optimal cutoff to distinguish transient from permanent injuries, with 90.0% sensitivity and 81.8% specificity. DISCUSSION Regardless of the technique used, the induced nerve injury aligns with axonotmesis, characterized by spontaneous recovery over time. To accurately evaluate functional recovery, a minimum postoperative observation period of 4 weeks is recommended. This model is best suited for assessing rapid-acting agents, as spontaneous recovery may obscure the effects of slower-acting treatments.

Objectives: This study aimed to analyze the clinical presentation, diagnostic process, therapeutic approaches, pathological features, and treatment outcomes of children diagnosed with Wilms tumor (WT) and evaluate the time intervals from symptom onset to seeking medical attention and subsequent diagnosis. Patients and methods: This retrospective study reviewed the records of 18 children (11 males, 7 females; median age: 3.72 years; range, 0.13 to 8.33 years) diagnosed with WT who underwent surgery between January 1, 2010, and December 31, 2023. Data on demographics, clinical presentation, treatment, and outcomes were collected and analyzed. All patients underwent radical nephrectomy and received preoperative and postoperative chemotherapy as per the UMBRELLA protocol of the International Society of Pediatric Oncology Renal Tumor Study Group. Results: The median age at diagnosis was 37 months. The most common presenting sign was a palpable abdominal mass (100%), followed by abdominal swelling (61%) and distension (67%). The mixed histopathological type was most prevalent (50%). The median time from symptom onset to seeking medical attention was 13.9 days, and the median from initial medical consultation to diagnosis was 9.9 days. Complications occurred in three (17%) patients, and one (6%) patient experienced relapse. The survival rate was 94%. Conclusion: This study's survival and relapse rates are comparable to global data, reflecting advances in the diagnosis and management of WT at our institution. However, further research is needed to address the study’s limitations and enhance outcomes, particularly in resource-limited settings.

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  .

Melanoma is a malignant tumor derived from melanocytes, predominantly located in the skin and mucosal surfaces. Although this cancer can spread to multiple organs, isolated metastasis to the spleen is exceptionally uncommon. When splenic involvement does occur, it typically forms part of widespread systemic dissemination, rather than appearing as a solitary lesion. This report discusses a 62-year-old male who underwent elective splenectomy following the discovery of a suspicious splenic mass. Three years earlier, he underwent excision of a pigmented nodular lesion in the right pectoral region. Histopathology revealed superficial spreading melanoma, Clark III, Breslow II, with 0.8 mm margins and no lymphovascular invasion, microsatellitosis, or mitoses. Re-excision and right axillary dissection confirmed metastatic melanoma in one of eight lymph nodes. Examination of the resection margins of the re-excised specimen showed no evidence of increased melanocytic activity. A follow-up abdominal CT identified a 7 mm, well-circumscribed, hypodense lesion in the inferior pole of the spleen, which lacked contrast enhancement. Due to inconclusive findings on both CT and ultrasound, surgical removal of the spleen was performed. Subsequent histological and immunohistochemical evaluation confirmed the lesion to be metastatic amelanotic melanoma (ICD-O code M8770/6). Solitary metastasis to the spleen from melanoma remains a clinical rarity and often manifests several years after the initial diagnosis. In such cases, surgical excision is considered the preferred treatment, offering potential for extended survival in the absence of additional metastatic disease.

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 assess Qualitiy of life (QoL) in adults by comparing two groups, the one with diagnosed hearing loss (HL) and the other without hearing complaints. Methods This cross-sectional study included 110 consecutive voluntary adult  patients divided in two groups: patients with hearing loss and control group. All participants , after examination , answered to a questionnaires on sociodemographic, clinical data and the World health Organization Quality of Life- Short version (WHOQOL-BREF). Results: Among 110 adults  participants, 59  were with hearing loss (hearing loss group – HLG) and 19  in hearing loss  with hearing aid group (HLHAG) and 51 in control group.  Consistently  higher score  in the domains of physical health (p=0.036) and psychological health (p=0.024) in control group was found; other domains did not reach statistical significance Significant differences between the HLHAG and control group in physical health (mean difference = -11.3; p=0.036) and psychological health (mean difference = -11.3; p=0.029) was confirmed. Conculsion Hearing loss could decrease QoL. Therefore, it is very important to recognize hearing impairment in a timely manner and to take a serious approach to treatment.

There is little research on sexting in the LGBTQ+ population, especially among LGBTQ+ adolescents and emerging adults who face particular challenges such as body image concerns. The aim of this study was therefore to investigate the role of body image factors (body surveillance, body shame, control beliefs) in predicting sexting motivations and behavior in LGBTQ+ youth, adolescents and emerging adults. A total of 847 LGBTQ+ individuals (366 adolescents and 481 emerging adults) from Bosnia and Herzegovina and Croatia participated in the online study. The results suggest that, on average, LGBTQ+ adolescents are more motivated to sext than LGBTQ+ emerging adults, but do not differ in the frequency of sexting behavior. The body shame was significantly positively correlated with sexting motivation, while other body-related variables were not correlated with sexting (motivation and behavior). Additionally, among adolescents, control beliefs were negatively correlated with sexting motivation. The strength of these correlations differs between adolescents and emerging adults and is stronger in adolescents. The results of this study provide novel evidence of the complex interplay between body image and sexting motivation and behavior in adolescents and emerging adults, highlighting that body variables are generally more important for adolescents than for emerging LBTQ+.