Differentiated or HPV‐independent vulvar intraepithelial neoplasia (dVIN) can progress rapidly to invasive cancer and accurate pathological diagnosis is essential to facilitate appropriate interventions. Histological similarities of dVIN with non‐neoplastic lesions, however, often make the diagnosis less reproducible. We investigated among a diverse group of pathologists whether the diagnostic agreement improves with the use of p53 immunohistochemistry (IHC) interpreted using the pattern‐based schema.

Spondylosis deformans (SD) is a common form of degenerative spinal disease in dogs, characterized byosseous bridging between vertebral bodies. This study focused on the lumbar and lumbosacral regions ofthe spine and analyzed radiographic records of 35 dogs of various breeds and age groups over a 12-monthperiod. Computed tomography (CT) was selectively employed in cases where radiographic interpretationwas inconclusive. The objective was to determine lesion localization and assess associations with breed, age,and gender. Findings showed that German Shepherds were most frequently diagnosed with SD, followedby Labrador Retrievers and mixed-breed dogs. Age distribution indicated that no cases were observed indogs aged 1-2 years, while the highest prevalence occurred in the 7-10-year age group. Lesion localizationdata revealed that the L4-L6 region was most commonly affected. These results highlight the age-relatedprogression of SD and its predilection for the lumbar spine, offering valuable insights for clinical assessmentand management in veterinary practice.

This study focuses on evaluating the antioxidant activity of pomegranate (lat. Punica granatum L.) peel extracts obtained through various extraction methods, including ultrasound-assisted extraction (UAE), Soxhlet extraction, and maceration, using methanol and 96% ethanol as solvents. These techniques were chosen for their differing effects on the preservation of thermosensitive phytochemicals. Antioxidant potential was assessed using the DPPH radical scavenging assay, with absorbance measured at 517 nm using a UV-Vis spectrophotometer. The results demonstrated that the efficiency of antioxidant activity largely depended on the extraction method and solvent used. A lower IC50 value indicates higher antioxidant activity, as it reflects a greater efficiency in neutralizing free radicals at a lower concentration. Extracts obtained by ultrasound-assisted extraction exhibited the highest radical scavenging capacity with an IC50 value of 19.049 μg/mL, while those obtained by Soxhlet extraction with ethanol showed comparatively weaker activity with an IC50 value of 34.210 μg/mL, likely due to the thermal degradation of sensitive bioactive compounds. The maceration method, although mild and solvent-efficient, yielded moderate antioxidant activity, highlighting the balance between extraction intensity and preservation of functional constituents. The study emphasizes the importance of optimizing extraction conditions to maximize the recovery of bioactive compounds from plant materials. Given the phytochemical richness and biological potential of pomegranate peel, the findings support its application as a natural source of antioxidants in the development of dermocosmetic and pharmaceutical formulations aimed at combating oxidative stress and disorders related to hyperpigmentation and skin aging.

BACKGROUND It has long been hypothesized that increasing heritability with age of cognitive and educational performance is partly attributable to evocative gene-environment correlation. However, this hypothesis has not been widely tested. METHODS We addressed this gap by examining whether children's education polygenic scores (PGSedu) were associated with maternal self-reported positive and literacy-focused parenting when children were 5 years old, and if evoked parenting differences mediated genetic effects on children's educational outcomes (mother-reported at 6-8 years of age), while controlling for parental PGSedu. We also investigated whether maternal reports of children's language at 5 years old were associated with parenting and mediated genetic effects on educational performance. These questions were addressed in a sample of 83,627 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study, a longitudinal population-based pregnancy cohort. RESULTS Children's PGSedu were significantly associated with maternal literacy-focused (β = .03, 95% CI [0.01, 0.05], p = .021) but not positive parenting (β = 0.01, 95% CI [-0.02, 0.05], p = .410), and literacy-focused parenting significantly mediated the effects of children's PGSedu on their educational performance (β = 0.01, 95% CI [1 × 10-3, 0.01], p = .023). Children's language was associated with maternal parenting and mediated the effects of children's PGSedu on their educational performance (β = 0.01, 95% CI [3 × 10-3, 0.02], p = .002). CONCLUSIONS These findings support our hypotheses and suggest early language and parenting may be mechanisms implicated in the pathways from children's genetics to their educational outcomes.

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.