Yeditepe University

Purpose: To describe clinical and virologic outcomes after topical 5% imiquimod for VaIN (vaginal intraepithelial neoplasia) within routine clinical practice, including the assessment of available post-treatment high-risk HPV status, and to evaluate its relationship with treatment outcomes. Methods: In this retrospective-cohort study, twenty patients with histologically confirmed VaIN (low-grade VaIN = 10, high-grade VaIN = 10) were evaluated between October 2020 and October 2022. The treatment varied based on the initial VaIN grade. The primary endpoint was complete response, defined as negative cytology and/or benign follow-up biopsy. Secondary endpoints included partial response (downgrading from high-grade to low-grade), persistence/progression, adverse events, and available post-treatment high-risk HPV status. Results: Among seventeen evaluable patients, a complete response was observed in 69.2% (9/13) imiquimod-treated patients. In high-grade VaIN imiquimod-treated patients, complete response was observed in 66.7% (6/9), while 33.3% (3/9) downgraded to low-grade VaIN on biopsy as a secondary outcome, with no persistence over a median follow-up of 24 months. Low-grade VaIN showed 75% clearance with either imiquimod or observation at a median follow-up of 24 months. In one low-grade imiquimod-treated, persistent HPV16 was observed, and the lesion progressed to high-grade VaIN; however, no invasive cancers were observed during follow-up. Adverse events related to imiquimod were mild; there were no discontinuations. Among baseline high-risk HPV positive imiquimod-treated patients, post-treatment follow-up HPV testing was available in a limited subset group, and clearance was confirmed in 44% (4/9) among those with follow-up testing and presented descriptively as exploratory. Conclusions: In this single-center retrospective cohort, outcomes after topical 5% imiquimod are reported as observed findings. Complete and partial responses were observed in high-grade VaIN with acceptable tolerability and no invasive events at available intermediate follow-up (median 24 months). Post-treatment HPV testing provided complementary virologic information alongside clinical outcomes, consistent with recommendations incorporating HPV testing into VaIN follow-up, and longer surveillance is required to assess long-term oncologic outcomes.

Gold nanoparticles (AuNPs) are used in biomedical applications. Due to data gap for safety of them, this research aimed to evaluate both AuNPs and oligonucleotide coated AuNPs (O-AuNPs) at 100, 500, and 2500 µg/kg doses in rats. Oxidative stress parameters, cytokines, 3-Nitrotyrosine, and metallothionein levels were also measured. There were significant changes in catalase, superoxide dismutase and malondialdehyde in erythrocyte, liver, kidney and brain tissues of rats. Liver metallothionein decreased in the lowest dose AuNPs, lowest and mid-dose O-AuNPs. As a result, AuNPs seem to have some adverse effects on oxidative stress parameters. Further researches are needed to elucidate the safety of AuNPs and O-AuNPs.

This ethnographic case study investigates the home–school transition of bilingual children from under-schooled multilingual households in Türkiye, with attention to families' and teachers' perspectives on literacy and schooling. Guided by ecological theory and a sociocritical literacy framework, the study examines the reconstruction of relationships among participants as they encounter converging or conflicting messages about literacy and schooling across home and school settings during the first year of education. Data from semi-structured interviews and participatory observations were analyzed through discourse analysis to explore the role of language in constructing social identities and practices. Findings show that participants negotiate positions across contexts and how possibilities for agency are enabled or constrained through the interaction of home and school practices.

White matter microdissection represents a valuable method for studying the three-dimensional organization of the human brain. Building on Klingler's classical technique, this approach has regained importance as both a research and educational tool in microneurosurgery. While the white matter dissection of the lateral aspect of the brain has been extensively described, the medial surface has received comparatively less attention. This article represents the second part of a three-paper series on white matter microdissection. It provides a structured, step-by-step demonstration of the dissection of the medial aspect of the brain, with a specific focus on the limbic lobe. As in the first paper, the core content is the supplementary video, which, through editing and annotation, has an enhanced didactic value. The dissection was performed according to the Klingler technique and recorded during the 8th Sulci, Gyri, Ventricles and Fiber Dissection Hands-on Course (Taipei, 2025). The procedure was conducted under microscopic magnification and edited into a didactic video presentation. All identifiable participants provided informed consent for publication. The dissection proceeds through nine main stages, beginning with the identification of the medial sulci and gyri and continuing with the sequential removal of cortical layers and white matter bundles. This systematic approach exposes the cingulum, inferior longitudinal fasciculus, callosal fibers, hippocampal formation, tapetum, thalamic peduncles, and mammillothalamic tract, illustrating the organization of the limbic lobe and the relationships between major white matter tracts and the ventricular walls. This work presents a comprehensive and didactic video demonstration of the medial hemispheric white matter dissection, highlighting the continuity and spatial relationships of limbic and periventricular structures. It contributes to a systematic and anatomically grounded understanding of cerebral white matter organization and supports the educational role of white matter microdissection in neurosurgical anatomy.

We investigate the initial-boundary value problem for the nonlinear viscoelastic Kirchhoff-type wave equation\begin{equation*}u_{tt} - \left(1 + \|\nabla u(t)\|^2 \right) \Delta u + \int_0^t g(t - s) \Delta u(s) \, ds + \alpha u_t = |u|^{p-1} \ln |u|, \quad x \in \Omega, t > 0,\end{equation*}with homogeneous Dirichlet boundary conditions. Local existence and uniqueness of weak solutions are established via a Banach fixed-point argument. Moreover, we prove a finite-time blow-up result: if the initial energy is positive and the data satisfy a compatibility condition, the solution’s $H_0^1$-norm becomes unbounded in finite time. This work extends existing results by capturing the combined effects of Kirchhoff-type nonlinearity, viscoelastic damping, and a logarithmic source.

Hydrolyzed collagen peptides (HCP) are widely used as bioactive ingredients in anti-aging and skin rejuvenation formulations due to their role in supporting skin hydration, elasticity, and extracellular matrix integrity. However, their high hydrophilicity limits effective incorporation into lipid-based systems, and restricts controlled release from formulations. In this study, ethosomal nanocarriers were designed as a phospholipid-ethanol-based system to promote favorable molecular interactions with hydrophilic peptides, aiming to enhance the encapsulation, stability, and controlled release of HCP for dermocosmetic applications. HCP-loaded ethosomes were prepared using phospholipid (Lipoid P75) and ethanol and optimized by varying high-pressure homogenization cycles. Physicochemical properties, including vesicle size, distribution uniformity, zeta potential, pH, and long-term stability, were monitored for up to 180 days. Vesicle morphology and peptide-lipid interactions were characterized using cryo-scanning electron microscopy and FTIR spectroscopy. Encapsulation efficiency was determined by ultrafiltration, while cytocompatibility was assessed in HaCaT keratinocyte cells. In vitro release behavior was investigated using Franz diffusion cells and compared with aqueous HCP solutions. All formulations exhibited nanoscale size distribution and high colloidal stability, with negative zeta potentials ranging from -42.9 to -76.7 mV. The optimized formulation demonstrated sustained encapsulation efficiency (73% after 180 days) and preservation of peptide structure, as confirmed by FTIR, indicating effective chemical stabilization within the ethosomal matrix. Cytotoxicity studies confirmed good skin cell compatibility. In vitro release studies revealed a controlled and prolonged release profile from ethosomal carriers compared with free HCP solutions, suggesting improved topical bioavailability of collagen peptides. To the best of our knowledge, this work provides one of the first systematic investigations of optimized ethosomal systems for the stabilization of hydrophilic collagen peptides as anti-aging dermocosmetic ingredients. These findings demonstrate that optimized HCP-loaded ethosomes represent a promising ingredient formulation platform enabling bioactive preservation, formulation stability, and controlled topical performance for collagen-based skin rejuvenation applications.

<title>Abstract</title> Breast cancer is among the leading causes of cancer mortality worldwide, with aging as a major risk factor. Caloric restriction (CR) is a well-established non-pharmaceutical intervention that extends healthspan and delays tumorigenesis, yet the systemic molecular mechanisms remain elusive. Both chronic and intermittent CR influence metabolic homeostasis, but their long-term effects on circulating miRNAs in breast cancer predisposition are unclear. Here, we examined how chronic and intermittent CR and subsequent refeeding remodel circulating miRNA networks in a tumor-free, breast cancer-prone transgenic mouse model. Blood samples were collected and circulating miRNA expression levels were determined at weeks 10 (baseline), 49 (adult), and 81 (old) using GeneChip miRNA 4.1 Array. Differential expression and target enrichment analysis were performed to identify age- and diet-associated modulatory patterns. Aging was associated with notable alterations in circulating miRNAs, and validated targets were enriched in the regulation of neurogenesis, MAPK, and FoxO signaling. Both chronic and intermittent CR reshaped these age-associated alterations, with the regulation of neurogenesis emerging as a key regulatory pathway. The effects were most pronounced at adult age rather than old age, while refeeding phase of the intermittent CR partially preserved the CR-induced miRNA patterns. Integrative analyses identified ten core miRNAs, where CR counteracted the expression patterns induced by aging, suggesting shared molecular mechanisms connecting aging, diet, and breast cancer risk. Our findings demonstrate that chronic and intermittent CR modulate circulating miRNAs in an age-dependent manner. These circulating miRNAs may act as systemic mediators linking to CR to neuroendocrine homeostasis and reduced breast cancer susceptibility.