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Risk factors for human papillomavirus positivity in a tertiary care center: A case–control study incorporating genotype distribution, co-infection patterns, and quantitative viral load analysis
(MDPI Publishing, 2026) Karalök, Mete Hakan; Dündar, Bağnu; Parmaksız, Ayhan; Gök Yurttaş, Asiye
Background/Objectives: Human papillomavirus (HPV) is the leading cause of cervical cancer and anogenital malignancies, yet its clinical presentation, genotype distribution, co-infection patterns, and viral load are poorly characterised in tertiary-care referrals. This study aimed to identify predictors of HPV positivity and describe genotype, co-infection, and relative viral copy number (Cq values) in this setting. Methods: A retrospective case–control study of 234 patients (97 HPV-positive, 137 HPV-negative) used a 37-genotype qPCR platform at a tertiary-care hospital between January-December 2025. Demographic data, clinical diagnosis categories, genotype profiles, co-infection patterns, and cycle quantification (Cq) values were recorded, and multivariable logistic regression identified independent predictors of HPV positivity. Results: HPV positivity was 41.5% (97/234). Only the clinical diagnosis category independently predicted HPV status. Compared with non-specific presentations, patients with anogenital or viral warts (aOR: 4.25; 95% CI: 1.49–12.14; p = 0.007) and vaginal or vulvar inflammation (aOR: 2.08; 95% CI: 1.19–3.63; p = 0.010) had higher odds of positivity. High-risk genotypes were the second most frequently detected category (40.00% of detections), after low-risk genotypes (48.21%), with HPV-16 leading among high-risk types. Co-infection occurred in 44.3% of HPV-positive patients, mostly involving mixed-risk genotypes. Patients with anogenital warts had lower Cq values than those with urinary tract complaints (p = 0.011), reflecting higher relative viral copy numbers per swab. Conclusions: HPV positivity and relative viral copy number (as approximated by Cq values) tracked more closely with clinical presentation than with demographic background. The dominance of low-risk and high-risk genotypes and the prevalence of mixed-risk co-infections were consistent with the symptomatic profile of the cohort. These findings support interpreting HPV results in light of clinical presentation and extended genotyping with relative viral copy number quantification in tertiary settings.
Microbiota signatures and genetic risk in pediatric celiac disease
(Baishideng Publishing Group Inc., 2026) Akçin, Rüveyda; Sarıbaş, Suat; Kocazeybek, Bekir
Celiac disease (CD) is a chronic, immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals, most commonly those carrying human leukocyte antigen-DQ2 or human leukocyte antigen-DQ8 hap lotypes. However, because these haplotypes are prevalent in the general population while only a minority of carriers develop disease, additional factors are likely to contribute to disease onset and progression. In recent years, the gut microbiota has emerged as a potential mediator between host genetic suscept ibility and environmental triggers, particularly in pediatric CD. Current evidence suggests that children with CD exhibit reduced microbial diversity, depletion of beneficial commensals, enrichment of proinflammatory taxa, and broader alte rations extending to fungal and viral communities. However, these findings re main heterogeneous, largely due to variability in study design, sampling sites, diet, age, and analytical methods. This review examines the interplay between host genetic risk and the intestinal microbiota in pediatric CD, with emphasis on bacterial, fungal, and viral components. Moreover, it highlights the importance of longitudinal, functionally oriented, and multi-omics approaches, particularly in genetically at-risk yet clinically unaffected children, to better clarify causality and identify early microbial markers of disease susceptibility.
Age and follicle-stimulating hormone as variables independently associated with serum anti-müllerian hormone in women attending a tertiary gynaecology clinic: A retrospective cross-sectional study using censoring-aware modelling
(MDPI Publishing, 2026) Karalök, Mete Hakan; Dündar, Bağnu; Parmaksız, Ayhan; Elgün, Tuğba; Koçyiğit Sevinç, Sevgi; Gök Yurttaş, Asiye
Objective: Anti-Müllerian hormone (AMH) is the most widely used biochemical marker of ovarian reserve, but its associations with other reproductive hormones are usually examined one hormone at a time and without accounting for values reported at the assay floor. This study examined the associations between serum AMH and age, follicle-stimulating hormone (FSH), luteinising hormone (LH), estradiol, progesterone and prolactin in women attending a tertiary gynaecology clinic. Materials and Methods: In this retrospective, cross-sectional, single-centre study, the records of women who underwent serum AMH testing together with a reproductive hormone panel between 1 January 2020 and 31 December 2025 were reviewed. Women with polycystic ovary syndrome, primary ovarian insufficiency, pregnancy or previous ovarian surgery were excluded. Bivariate associations were assessed with Pearson and Spearman correlation coefficients on raw and Box–Cox-transformed variables. Because 12.82% (n = 15) of AMH results were left-censored at the analytical reporting floor of 0.02 ng/mL, a multivariable Tobit model with the censoring limit specified on the Box–Cox-transformed scale (λ = 0.309, threshold = −2.270) was fitted, with predictors selected a priori on clinical grounds. Sensitivity analyses examined the influence of high AMH values, an alternative transformation of AMH, and flexible modelling of age. Results: The analysis included 117 women aged 18–45 years. Mean AMH was 2.22 ± 2.24 ng/mL [median 1.61 ng/mL (Q1–Q3, 0.36–3.20)]. In bivariate correlation analysis, AMH showed statistically significant inverse associations with age (r = −0.376, p < 0.001) and FSH (r = −0.445, p < 0.001), whereas LH, estradiol, progesterone, and prolactin showed no statistically significant correlations with AMH (all p > 0.10). In the multivariable Tobit model, only age (β = −0.068; 95% CI [−0.117, −0.018]; p = 0.007) and transformed FSH (β = −3.582; 95% CI [−4.846, −2.317]; p < 0.001) remained independently associated with transformed AMH. LH, estradiol, progesterone, and prolactin were not independently associated with AMH in the multivariable model (all p > 0.05). The standardised association was greater for transformed FSH (β* = −0.559) than for age (β* = −0.234). The associations of age and FSH were consistent in direction and magnitude across all sensitivity analyses. Conclusions: In this selected clinical sample, age and FSH were the only variables independently associated with serum AMH after mutual adjustment. LH, estradiol, progesterone, and prolactin showed no statistically significant associations with AMH in either the unadjusted bivariate analyses or the multivariable model. The absence of independent associations for these hormones should be interpreted cautiously because hormone sampling was not standardised to menstrual cycle day, which may have introduced measurement variability. These findings describe associations within the study population and do not establish causal relationships, reference intervals, or a basis for modifying testing strategies. The analysis also highlights the importance of accounting for left-censoring when modelling AMH data containing a substantial proportion of results at the assay reporting floor.
DNA methylation of ANKRD23 as a novel biomarker for early diagnosis of ovarian cancer
(Women's Health and Action Research Centre, 2026) Alizada, Aydan; Şükrüoğlu Erdoğan, Özge; Kılıç Erciyas, Seda; Çelik Demirbaş, Betül; Pasin, Özge; Dinç, Ahmet; Saip, Pınar; Yazıcı, Hülya; Tuncer, Şeref Buğra
Ovarian cancer (OC) is a leading cause of gynecologic cancer-related mortality and is frequently diagnosed at advanced stages due to the absence of effective early detection tools. Epigenetic alterations, particularly DNA methylation, play a critical role in tumorigenesis and represent promising non-invasive biomarkers. This study investigated the methylation status of the ANKRD23 gene in OC and evaluated its diagnostic potential using peripheral blood samples. A total of 385 serous OC patients, 50 individuals with benign ovarian conditions, and 99 healthy controls were included. DNA methylation was assessed using methylation-sensitive restriction enzymes followed by real-time PCR. ANKRD23 methylation was significantly associated with clinical stage (p = 0.029), histological grade (p = 0.009), and ethnicity (p = 0.024). Moreover, methylation levels differed significantly among OC patients, benign cases, and healthy controls (p = 0.026). These findings support blood-based ANKRD23 methylation as a promising biomarker for non-invasive ovarian cancer diagnosis and risk stratification. (Afr J Reprod Health 2026; 30 [15] 16-25).
Association of vestibule depth with peri-implant inflammation and soft tissue stability independent of keratinized mucosa width: A cross-sectional study
(Korean Academy of Periodontology, 2026) İnan, Berkin; Parlak, Hanife Merva; Akçiçek, Gökçen; Güncü, Mustafa Barış; Akman, Abdullah Cevdet; Parmaksız, Ayhan; Keçeli, Hüseyin Gencay; Güncü, Güliz Nigar
Purpose: This study evaluated whether vestibule depth (VD) affects peri-implant inflammation and mucosal margin stability in the posterior mandible independently of keratinized mucosa width (KMW). Methods: A total of 129 patients, each with a single implant in the mandibular premolar or molar region, were included. Clinical variables, including gingival index, plaque index (PI), peri-implant probing depth, clinical attachment level (CAL), gingival bleeding time index (GBTI), VD, KMW, mucosal thickness (MT), mucosal recession (MR), peri-implant soft tissue phenotype, and peri-implant soft tissue dehiscence (PISTD), were assessed. Multiple linear regression analysis was performed to determine the associations of GBTI, MR, and PISTD type with the independent variables PI, KMW, age, implant diameter, sex, function time, implant location, CAL, MT, VD, and phenotype classification. Results: Implants with adequate KMW (≥2 mm) displayed greater VD and MT, less MR, and a thicker phenotype than implants with inadequate KMW (<2 mm) (P<0.001 for all). PISTD class II defects were observed more frequently in the group with adequate KMW, whereas class III defects were more common among the patients with inadequate KMW (P=0.001). Implants with sufficient VD (≥6 mm) showed greater KMW and MT and less MR than implants with insufficient VD (<6 mm) (P=0.026 for MR; P<0.001 for all other comparisons). Based on the multiple regression analysis, KMW was significantly associated with GBTI, MR, and PISTD types and subtypes (P<0.05 for all), whereas VD was not significantly associated with any of these variables. Conclusions: VD was not significantly associated with peri-implant inflammation or soft tissue stability, whereas KMW showed a stronger association with these parameters. These findings suggest that KMW, independent of VD, plays an important role in peri-implant soft tissue health in the posterior mandible.
Strain-dependent differences in neuroplasticity markers related to memory
(İnönü University Faculty of Medicine, 2026) Dursun, İlknur; Kılıç, Ertuğrul; Elibol, Birsen
Aim: Spatial learning and memory both rely critically on hippocampal plasticity which are a core feature of several neurological and psychiatric disorders; but commonly used different rat strains might exhibit differences in these processes which may influence the translational relevance of preclinical findings Herein, we examined the long-term spatial memory of adult Wistar (n=5), Sprague Dawley (n=6), and Long Evans (n=5) rats, and their hippocampalexpressionoftwo plasticity markers: brain-derivedneurotrophicfactor (BDNF) and doublecortin (DCX). Materials and Methods: TheanimalsweretrainedintheMorriswatermazeforfourdays, followed by a probe trial with no platform. Hippocampal BDNF and DCX protein levels were quantified by Western blotting. Results: All strains learned the task, as indicated by a decrease in escape latency and swim distance over time. Sprague Dawley rats swam faster than the other strains, sug gesting that swim distance evaluates learning independently of speed. On the first train ing day, Wistar rats swam the shortest distances, whereas by the final day Long Evans rats did. In the probe trial, Sprague Dawley rats spent a greater proportion of time in the target quadrant than Wistar rats did. Long Evans rats displayed an intermediate pattern. At the molecular level, Sprague--Dawley rats had higher hippocampal BDNF levels than Wistar and Long-Evans rats. DCX levels were higher in Sprague Dawley and Long Evans rats than in Wistar rats. Conclusion: These findings suggest that although all three strains can acquire and retain spatial memory under identical conditions, they differ in behavioral strategies and hip pocampal plasticity. Therefore, strain background should be carefully considered when designing and interpreting rodent studies of learning and memory.
Heterogeneous fatty acid-binding protein 4 (FABP4) responses after Roux-en-Y gastric bypass reveal adipokine remodeling dissociated from weight loss, inflammation, and incretin dynamics
(Oxford University Press, 2026) Çalıkoğlu, Bedia Fulya; Örskaya, Handan Hanım; Yenidünya Yalın, Gülşah; Barbaros, Umut; Bingül, İlknur; Aydın, Fatih
Background Fatty acid–binding protein 4 (FABP4) is an adipokine closely linked to adipose tissue mass, low-grade inflammation, and cardiometabolic risk. Following bariatric surgery, FABP4 is generally expected to decrease in parallel with weight loss and improvements in inflammation. However, whether postoperative FABP4 dynamics uniformly reflect these changes or exhibit heterogeneous patterns independent of anthropometric and hormonal adaptations remains unclear. Methods Twenty-eight adults undergoing Roux-en-Y gastric bypass (RYGB) were prospectively followed at baseline, 3 months, and 6 months. Anthropometric measures, body composition, metabolic indices, hsCRP, IL-6, fasting GLP-1 and PYY, and serum FABP4 were assessed. The 3-month time point was included to capture early postoperative metabolic and adipokine dynamics, whereas primary analyses focused on baseline-to-6-month changes to reflect more stable biological adaptations. Patients were classified as FABP4 responders (decrease from baseline to 6 months) or rebound/non-responders. Longitudinal changes were analyzed using Friedman tests, and between-group comparisons were performed using nonparametric methods. Results RYGB induced early and progressive anthropometric improvement, with BMI decreasing from 51.5 [48.1-55.2] kg/m2 at baseline to 42.8 [39.6-46.9] at 3 months and 35.6 [32.4-38.9] at 6 months (P < .001). Systemic inflammation improved in parallel: IL-6 declined from 3.18 [2.27-4.44] pg/mL at baseline to 2.95 [2.31-3.82] at 3 months and 1.68 [0.96-2.95] at 6 months (P = .00015), while hsCRP decreased significantly over time (P < .001). In contrast, FABP4 trajectories demonstrated marked inter-individual variability. At 3 months, FABP4 changes showed no consistent directional pattern, despite early weight loss and improvement in inflammation. By 6 months, 46% of patients exhibited no decrease or a rebound in FABP4 levels. FABP4 responders experienced less pronounced BMI reduction compared with rebound/non-responders (ΔBMI −14.2 [−16.8 to −11.9] vs −18.6 [−21.4 to −15.1] kg/m2; P = .03). Changes in FABP4 were not significantly correlated with changes in BMI, fat mass, hsCRP, or IL-6 (all P > .05). Fasting GLP-1 and PYY levels did not differ between FABP4 response groups. Conclusions Despite expected improvements in weight and systemic inflammation after RYGB, FABP4 responses are heterogeneous and only weakly related to anthropometric, inflammatory, or fasting incretin changes. These findings suggest that FABP4 reflects individualized adipose tissue–specific adaptive remodeling rather than a simple surrogate of weight loss or of improvements in inflammation following bariatric surgery.
Age-adjusted associations between routine systemic inflammatory markers and anti-müllerian hormone in reproductive-age women: A retrospective cross-sectional study
(MDPI Publishing, 2026) Karalök, Mete Hakan; Dündar, Bağnu; Parmaksız, Ayhan; Elgün, Tuğba; Gündoğan, Gül İpek; Gök Yurttaş, Asiye
Background: Anti-Müllerian hormone (AMH) is widely used as a marker of ovarian reserve and is strongly influenced by chronological age. Although inflammation has been implicated in ovarian aging and follicular dysfunction, whether routinely measured peripheral inflammatory markers provide additional information regarding AMH concentrations remains unclear. Objective: This study aimed to evaluate the age-adjusted associations of C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) with serum AMH concentrations in reproductive-age women. Methods: This retrospective cross-sectional study included women aged 18–45 years with available AMH, complete blood count, and CRP measurements. After reapplying the prespecified eligibility criteria and excluding confirmed data-entry or analytical errors, 819 women were included in the final analysis. NLR was calculated from absolute neutrophil and lymphocyte counts. Because CRP and NLR showed right-skewed distributions, Box–Cox transformations were applied. Associations with Box–Cox-transformed AMH were evaluated using an age-adjusted left-censored Tobit regression model. Results: The mean age of the participants was 34.07 ± 6.94 years, and the median AMH concentration was 1.07 ng/mL (interquartile range, 0.29–2.50). Chronological age was inversely associated with AMH (β = −0.123, 95% CI: −0.135 to −0.111, p < 0.001). After adjustment for age, neither CRP (β = −0.038, 95% CI: −0.085 to 0.009, p = 0.114) nor NLR (β = −0.012, 95% CI: −0.222 to 0.198, p = 0.912) was independently associated with AMH. Conclusions: In this retrospective outpatient cohort, routine peripheral inflammatory markers did not explain additional variation in AMH beyond chronological age. These results do not exclude a potential role for local ovarian inflammation, which may not be adequately captured by peripheral CRP or NLR measurements.
Blood-based RBBP7 and RIBC1 methylation as a candidate epigenetic biomarker for ovarian cancer epigenetic markers RBBP7 and RIBC1 in ovarian cancer
(Springer Nature Link, 2026) Şükrüoğlu Erdoğan, Özge; Kılıç Erciyas, Seda; Çelik Demirbaş, Betül; Dinç, Ahmet; Ünal, Elif; Güngör Uğurlucan, Funda; Akdeniz Ödemiş, Demet; Pasin, Özge; Saip, Pınar Mualla; Yazıcı, Hülya; Tuncer, Şeref Buğra
Background: Ovarian cancer (OC) remains one of the leading causes of gynecological cancer-related mortality, with limited biomarkers for early detection and prognosis. Changes in DNA methylation-stable and detectable in blood-are potential candidates for clinical application. In our earlier genome-wide methylation study involving monozygotic twins where one had ovarian cancer and the other did not, we identified two genes, RBBP7 and RIBC1, as differentially methylated. These findings laid the groundwork for further targeted investigation. Methods and results: Peripheral blood methylation of RBBP7 and RIBC1 was evaluated in 387 ovarian cancer patients, 50 benign ovarian disease patients, and 100 healthy controls using a bisulfite-free, methylation-sensitive restriction enzyme (MSRE)-based qPCR assay. In this approach, DNA is divided into digested and undigested reactions, and methylation levels are calculated from Ct differences. Methylation levels differed across groups, with RBBP7 showing a clearer discriminatory pattern (p < 0.001) and associations with disease severity (p < 0.001) and CA125 levels (p = 0.05). RIBC1 also differed between ovarian cancer and healthy controls (p < 0.001) but showed no significant associations with clinicopathological parameters. Conclusion: RBBP7 methylation appears to be a potential candidate biomarker associated with disease characteristics and progression patterns of ovarian cancer. These findings suggest that RBBP7 methylation may have potential for integration into future multi-marker diagnostic and risk-stratification approaches, pending further validation. While RIBC1 methylation also showed differential patterns, its clinical relevance appears limited and requires further investigation. These findings support the integration of RBBP7 methylation assessment into early-stage diagnostic workflows and risk-stratification strategies for ovarian cancer, enabling more precise clinical decision-making. Future multicenter prospective studies are warranted before clinical implementation.
Circulating microRNAs as promising biomarkers in parkinson’s disease
(Springer Nature Link, 2026) Kaya, İbrahim Alper; Demircan, Berna; Özdilek, Fatma Betül; Baran, Mustafa; Doğan, Emine Sena; Koç Ada, Saniye; Bursa, Muhammet Çağlar; Kaya Bursa, Aslı Pelin; Öztekin, Zeynep; Gürvit, İbrahim Hakan
Our study aims to examine possible Parkinson Disease (PD)-related circulating microRNAs (miRNA) and their potential roles and use cases in screening, diagnosis, and the disease progress in Turkish population. For this purpose, we selected 7 promising candidates namely miR-16–1, miR-24-3p, miR-30a, miR-30e, miR-34a, miR-34b, miR-331 from multiple studies and bioinformatic web tools. For our study, 51 PD patients with no other severe disease except for hypertension and 20 healthy matching controls were included. Serum samples were collected from venous blood and stored properly. RNA extraction, reverse transcription and real-time polymerase chain reaction (qPCR) for each pre-determined miRNA were applied to all samples with a strong normalization method to determine expression levels. Additionally, validated miR-24-3p target genes were intersected against publicly available CSF proteomics (PXD011216), PBMC transcriptomics (GSE22491), and serum metabolomics (MTBLS10958) datasets. miR-24-3p expression was also examined in two independent miRNA datasets (GSE269775; GSE16658). Statistical analyses were done using SPSS and Qiagen GeneGlobe webtools. Between PD and the control group, miR-24-3p serum levels were found increased 1.7 times (p = 0.0001). Among patients, miR-331 serum levels changed significantly with UPDRS scores (p = 0.027). Multi-omics analysis identified 21 differentially abundant miR-24-3p target proteins in PD CSF (81% downregulated), three cross-platform concordant targets, and five metabolically linked pathways. miR-24-3p levels may differ in different biological compartments in PD. In serum, miR-24-3p may provide significant value as a diagnostic biomarker with 80.4% sensitivity and 85% specificity. miR-331 might be a candidate for predicting the severity of the disease.
Neurodevelopmental outcomes relevant to autism in juvenile mice exposed to PCB 11 in the maternal diet throughout gestation and lactation
(Frontiers Media S. A., 2026) Wilson, Rebecca J.; Panesar, Harmanpreet K.; Dursun, İlknur; Mendieta, Rosalia; Andrew, Peter M.; Li, Xueshu; Lehmler, Hans-Joachim; Lein, Pamela J.
Polychlorinated biphenyls (PCBs) pose a significant risk to the developing human brain, and recent epidemiological data suggest PCBs increase the risk and/or severity of neurodevelopmental disorders (NDD), including autism spectrum disorder (autism). Experimental animal studies confirm that PCBs disrupt neurodevelopment, resulting in behavioral deficits. Historically, research on the developmental neurotoxicity of PCBs has focused on the higher-chlorinated PCBs found in legacy commercial mixtures; however, lower-chlorinated PCBs (LC-PCBs), including congeners not present in commercial mixtures, predominate in contemporary human exposures. Previous in vitro studies demonstrated that one such LC-PCB, PCB 11, altered dendritic arborization, a cellular phenotype common to multiple NDD. Whether PCB 11 modulates dendritic morphogenesis in vivo is not known. In this study, we investigated how gestational and lactational exposure to PCB 11 in the maternal diet affected critical neurodevelopmental processes in juvenile male and female mice. C57BL/6J mouse dams were exposed to vehicle or PCB 11 at 0.1 or 1.0 mg/kg/d in their diet for 2 weeks prior to mating and throughout gestation and lactation. Brain tissue was collected from offspring at postnatal day (P)4 and P21 to assess dendritic arborization, apoptosis, glial reactivity, and neurogenesis in the hippocampus and neocortex. PCB 11 dose-dependently reduced the dendritic arborization of pyramidal neurons in the neocortex by 13-25% but had no significant effect on the dendritic morphogenesis of pyramidal neurons in the hippocampus. Apoptosis was not altered by PCB 11 in either brain region of either sex at either age. While PCB 11 had no effect on neurogenesis at P4, it dose-dependently decreased neurogenesis by 15-70% in the dentate gyrus at P21. GFAP immunoreactivity and the morphological complexity of astrocytes were increased by 40-60% and 20-60%, respectively, in the CA1 hippocampus of female mice exposed to 0.1 mg/kg/day PCB 11; in contrast, PCB 11 had no effect on IBA1 immunoreactivity. These findings demonstrate that developmental exposure to PCB 11 promoted NDD-relevant cellular phenotypes in a dose, sex, and region-dependent manner, providing experimental evidence in support of epidemiological data identifying PCBs as potential NDD risk modifiers. Ongoing studies are investigating behavioral responses in weanling mice developmentally exposed to PCB 11.
Chronic pantoprazole exposure induces behavioral deficits and region‑specific molecular changes in the rat motor cortex and cerebellum
(Nencki Institute of Experimental Biology, 2026) Çaglar, Emine; Elibol, Birsen; Polat, Nurhayat; Dursun, İlknur
Proton pump inhibitors are widely used, but their long‑term effects on the central nervous system are not well understood. In this study, we investigated whether chronic pantoprazole use alters sensorimotor function, oxidative stress, inflammatory response, and apoptosis in the motor cortex and cerebellum. Twenty‑one female Wistar rats were randomized to control (C), gavage control (GC), or pantoprazole (P; 20 mg/kg/day for 12 weeks) groups. Sensorimotor coordination (rotarod), water‑maze swim velocity, and open‑field locomotion were assessed as behavioral parameters. The cortical and cerebellar tissues were analyzed by Enzyme‑Linked Immunosorbent Assay (ELISA) for apoptosis, inflammation, and oxidative stress. Pantoprazole impaired sensorimotor coordination compared to both control groups. However, its effects on swim velocity and locomotor activity were primarily significant when compared to the naive control group, suggesting that gavage‑related stress may have contributed to these behavioral outcomes. Bcl‑2‑associated X protein (BAX) and Bcl‑2 associated agonist of cell death (BAD) protein levels and the BAX/Bcl‑2 ratio increased with pantoprazole, particularly in the motor cortex, indicating enhanced pro‑apoptotic activity. While tumor necrosis factor levels did not change, interleukin (IL)‑6 and IL‑1β levels were significantly higher in the cerebellum, suggesting neuroinflammatory activation associated with both pantoprazole and gavage‑induced stress. Furthermore, oxidative stress analyses revealed elevated malondialdehyde and oxidative stress index levels, as well as increased total antioxidant status, in specific regions, suggesting an imbalance between oxidative and antioxidant responses. Chronic pantoprazole administration resulted in modest motor deficits and region‑specific molecular alterations, including a pro‑apoptotic shift in the motor cortex. In addition, an inflammatory/compensatory antioxidant response in the cerebellum was observed due to both gavage‑induced stress and pantoprazole administration. These findings highlight the need for further studies on dose‑response, reversibility, and synaptic consequences, and suggest the importance of considering the risks of prolonged proton pump inhibitors exposure.
Fluoxetine attenuates hepatic ischemia–reperfusion injury through antioxidant, anti‑inflammatory and anti‑apoptotic mechanisms
(Springer Nature Link, 2026) Işık, Musab; Şahin, Gülderen; Kervancıoğlu, Gülnaz; Güner, İbrahim; Yaman, Muhittin Onur; Yelmen, Nermin
Hepatic ischemia–reperfusion injury is a major clinical problem associated with liver surgery, trauma, and transplantation, characterized by oxidative stress, inflammation, microcirculatory dysfunction, and apoptosis. Fluoxetine, a selective sero tonin reuptake inhibitor, has been reported to exert antioxidant, anti-inflammatory, and antiapoptotic effects. The present study aimed to investigate the potential protective effects of fluoxetine against experimental hepatic ischemia–reperfusion injury in rats. Male Wistar rats were randomly assigned to three groups: control, ischemia–reperfusion and fluoxetine-treated ischemia–reperfusion (n = 7 each). Hepatic ischemia–reperfusion injury was induced by infrarenal abdominal aortic cross clamping for 60 min followed by 120 min of reperfusion. Fluoxetine (20 mg/kg/day, intraperitoneal) was administered for three consecutive days prior to ischemia. Oxidative stress markers, antioxidant parameters, inflammatory and anti-inflamma tory cytokines, apoptotic markers, and specific tissue injury biomarkers were measured in liver homogenates using ELISA. Histopathological alterations were evaluated by light microscopy. Ischemia–reperfusion significantly increased oxidant markers, inflammatory cytokines, NF-κB activation, apoptotic indices, liver enzyme levels, and histological damage, while reducing antioxidant capacity. Fluoxetine treatment markedly restored antioxidant defenses, suppressed oxidative stress, inflammation, apoptosis, and microcirculatory injury, and significantly improved histopathological findings compared with the untreated ischemia–reperfusion group. Fluoxetine exerts a protective effect against hepatic ischemia–reperfusion injury through antioxidant, anti-inflammatory and antiapoptotic mechanisms, suggesting its potential as a therapeutic agent in conditions associated with hepatic ischemia–reperfusion.
Inhibition of c-jun n-terminal kinase attenuates diabetic testicular damage via endoplasmic reticulum stress reduction
(Universidad de la Frontera, 2026) Bayram, Şinasi; Ersoy, Onur; Deveci, Engin; Kızılay, Gülnur
The underlying causes of many diabetes-related complications are well known. However, the reasons for the complication related to male reproductive health remain unclear. Hyperglycemia disrupts the balance between oxidants and antioxidants, causing damage to cells, especially ER stress. ER stress triggered by the proteins accumulating in the ER lumen causes apoptosis by activating various pathways. c-Jun N-terminal kinase (JNK) is a key protein in systemic diseases like diabetes, and SP600125 is a widely used JNK inhibitor. This study focuses on whether JNK inhibition by SP600125 prevents diabetic testicular damage by reducing ER stress. In our study, animals were divided into three groups: Control group, the diabetes group, and the JNK inhibition group. Blood glucose level, body and testicular weights, and seminiferous tubule diameters were measured. Seminiferous tubules were evaluated by the Johnsen score in Hematoxyline and Eosin stained sections. Protein expressions of caspase 3, phospho (p)-JNK, caspase 12, and CHOP were evaluated. The Inhibitor group had significantly decreased active caspase-3, (p)-JNK, caspase-12, CHOP values, and blood glucose levels, increased body and testicular weights, seminiferous tubule diameter, and Johnsen score values compared to the diabetes group. JNK inhibition significantly ameliorated the histopathological damage in testicular tissue by preventing diabetes-induced ER stress and apoptosis.
The effects of early postnatal alcohol exposure on bone molecular composition in a mouse model
(Wiley, 2026) Dursun, İlknur; Elibol, Birsen; Garip Ustaoğlu, Şebnem
Background: Perinatal exposure to alcohol is a critical risk factor for long- term skeletal health in humans and has been demon strated in rodent models. Early postnatal alcohol gavage exposure in mice is used to study third trimester toxicity in humans. However, further research is required to fully characterize the effects of alcohol on bone molecular composition and distinguish them from the alterations associated with gavage- related stress in mouse models. Methods: Female mouse pups were assigned to untreated control (C), gavage control (GC), and alcohol- treated (A) groups. Between postnatal days 3 and 20, the A group received ethanol (3.0 g/kg/day) by intragastric gavage, while the GC group under went the same gavage procedure without any solution (neither milk nor ethanol). At postnatal day 90, femoral bone molecular composition and bone metabolism were evaluated by attenuated total reflection Fourier- transform infrared (ATR- FTIR) spec troscopy and biochemical studies. Results: Several ATR- FTIR- derived matrix and mineral- related alterations, including reduced total protein- related indices, lower collagen cross- link ratio, reduced mineral- to- matrix ratio, and increased crystallinity, were observed in both GC and A groups rel ative to untreated controls, indicating a substantial long- term influence of the gavage procedure itself. Compared with the GC, the A group showed additional selective differences, most notably reduced relative carbonate content and increased CTX- I levels. In the C group, serum 25(OH)D, PTH, and calcitonin levels differed from both GC and A groups, whereas osteocalcin was increased in the GC group relative to the C group, and no significant difference was observed between the GC and A groups. Conclusion: Prolonged neonatal gavage was associated with substantial long- term changes in bone molecular composition and several circulating bone- related hormonal markers. Against this background, postnatal alcohol exposure was associated with additional selective differences, particularly in CTX- I and relative carbonate content. These findings highlight the importance of discriminating between the effect of the procedure and the effect of alcohol in developmental models based on repeated neonatal gavage.
Investigation of volumetric alterations in thalamic subnuclei in progressive and stable mild cognitive impairment using magnetic resonance imaging
(İstanbul University Press, 2026) Harı, Emre; Soylu, Can
Objective: This study aimed to evaluate the volumes of thalamic subnuclei known to function in large-scale cognitive networks between progressive mild cognitive impairment (pMCI) and stable MCI (sMCI) groups progressing to dementia. Materials and Methods: Magnetic resonance imaging and clinical data of 31 pMCI (Age: 68.66±6.86; education: 15.71±2.46; gender: 15 female) and 31 sMCI (Age: 70.18±7.24; education: 16.23±2.68; gender: 13 female) patients with no statistically significant differences in age, gender, education, and follow-up interval (mean 21 months) from the Alzheimer's Disease Neuroimaging Initiative database were used. FreeSurfer software was used for individual thalamus segmentation and volume calculation. Thalamic nuclei were divided into anterior, medial, posterior, lateral, ventral, and intralaminar nucleus groups. The volumes of each nucleus were normalised using intracranial volume. Normalised volumes were compared between groups using independent samples t-test, and false discovery rate (FDR) correction was applied. Correlation analysis was performed using florbetapir (AV45) PET scores to evaluate the relationship between amyloid burden in the brain and volumetric decrease. Results: Statistically significant volumetric decreases were detected in the bilateral anterior (Right: t=2.432 pFDR=0.048; Left: t=2.327 pFDR=0.048) and lateral (t=2.372 pFDR=0.048) nucleus groups in pMCI compared to sMCI. A negative correlation was found between PET scores and bilateral anterior nucleus groups (Right: r=-0.353 p=0.026, left: r=-0.350 p=0.026). Conclusion: In our study, the anterior thalamic nucleus group, closely associated with memory, showed reduced volume in MCI patients who progressed to dementia, and this reduction correlated with amyloid burden in the brain. Based on the findings of our study, the anterior thalamic nucleus group may provide supportive value to other MRI biomarkers in predicting conversion to dementia.
Corrugator supercilii muscle and its relationship with neurovascular structures of the frontal region: A cadaveric study
(Springer Nature Link, 2026) Yıldız, Nilay; Nteli Chatzioglou, Gkionoul; Coşkun, Osman; Kale, Ayşin; Gayretli, Özcan
Background The corrugator supercilii muscle (CSM) is a critical anatomical target for botulinum toxin injections and surgical interventions in migraine treatment and facial rejuvenation. However, complications such as sensory loss or vascular injury may arise due to its proximity to neurovascular structures. This study aims to delineate the precise anatomy of the CSM and its relationship with the supratrochlear (STN) and supraorbital nerves (SON) to enhance procedural safety. Methods A cadaveric dissection was performed on 44 hemifaces of 22 formalin-fixed cadavers (11 male and 11 female). The CSM and adjacent neurovascular structures were dissected, photographed, and measured using ImageJ software. Morphometric parameters included distances related to the CSM, as well as branching patterns of the STN and SON were evaluated. Results The CSM length was significantly longer in females (30.53 ± 2.60 mm; 28.93 ± 2.15 mm, p = 0.032). The STN exhibited complex branching (> 3 branches) in 48% of cases, with 13.6% piercing the CSM anteriorly. The SON medial branch pierced the CSM’s lateral segments (46.5% 3rd segment; 53.5% 2nd segment). The supratrochlear artery crossed the CSM 14.84 ± 2.05 mm (females) and 15.43 ± 2.04 mm (males) from the midline, while the supraorbital artery lay 25.38 ± 3.76 mm (females) and 24.49 ± 4.55 mm (males) lateral to the midline. Conclusions The CSM’s intimate relationship with the STN, SON, and associated vessels underscores the risk of iatrogenic injury during forehead procedures. Anatomical variations in nerve branching and muscle morphology highlight the need for individualized approaches to botulinum toxin injection and surgical resection. These findings may reduce complications and improve outcomes in migraine surgery and aesthetic interventions. No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Grup D β-laktamazlar
(Akademisyen Kitabevi, 2026) Hasdemir Gökboğa, Münevver Ufuk; Gür, Deniz; Süzük, Serap
Class D β-lactamases, according to the Ambler molecular classification, are serine hydrolases like class A and C enzymes. Although evolutionarily related, they share less than 20% homology with classes A and C. Most class D β-lactamases are not inhibited by classical inhibitors like tazobactam, clavulanic acid, or sulbactam, but newer inhibitors such as avibactam and vaborbactam can be effective. Clinically important class D enzymes, especially OXA-type β-lactamases in gram negative bacteria, are mainly plasmid-encoded. OXA group β-Lactamases can be divided into three subgroups according to their action spectrum; 1. Narrow-spectrum OXA enzymes: they hydrolyze oxacillin and cloxacillin and are not inhibited by classical inhibitors, 2. Extended-spectrum OXA enzymes: they can hydrolyze third-generation cephalosporins, 3. Carbapenem-hydrolyzing OXA enzymes: they are clinically significant (e.g., OXA-23 in A. baumannii, OXA-48 in K. pneumoniae). Commercial immunochromatographic tests and MALDI-TOF MS can detect OXA enzymes. PCR-based methods, RT-qPCR, isothermal PCR, and microarrays remain the gold standard for specific detection.
LuminaConsent: AI-driven standardization and quality enhancement of urological informed consent documentation
(Kare Publishing, 2026) Topçu, İbrahim; Soylu, Tuncay; Şimşekoğlu, Muhammed Fatih; Tuzcu, Esra Melis; Salman, Zeynep; Demir, Perihan; Kaç, Beyzanur; Kartal, Muhammed Yusuf; Suzan, Serhat; Karaman, Muhammet İhsan
Objective: Informed consent is the cornerstone of modern medical ethics, but current documentation systems negatively impact patient autonomy and clinical quality due to deficiencies in readability, comprehensibility, and standardization. These is sues hinder patient participation and require innovative solutions. This study introduces the AI-powered LuminaConsent system to address standard deficiencies, comprehensibility issues, and efficiency constraints in urological informed consent documents. Methods: In a three-armed comparative study, LuminaConsent (artificial intelligence), Turkish Urological Surgery Asso ciation standard forms, and expert-developed documents were evaluated in 10 urological procedures. The system is based on the RAG architecture, which uses OpenAI’s GPT-4o-mini model and a special knowledge base consisting of 12 clinical publications. Three independent urology specialists conducted a blind evaluation using a 100-point scale across five areas: scientific content accuracy, patient communication effectiveness, quality of risk-benefit information, perioperative guidance, and legal-ethical compliance. RESULTS: LuminaConsent achieved higher performance with mean scores of 82.33 points (SD±4.2) versus 78.77 points (SD±6.1) for professional society standards and 57.43 points (SD±3.8) for specialist documentation, representing statisti cally significant improvements of 43.3% over specialist practices (p<0.001) and 4.5% over professional society standards (p<0.05). The system demonstrated consistent high-quality output across all procedures while generating comprehensive documentation within 96-180 seconds compared to traditional processes requiring multiple days. Conclusion: LuminaConsent offers a pioneering model for systematic AI integration in clinical practice with its evidence based content generation and bilingual processing capabilities. The findings support the potential to empower patient auton omy, reduce application variations, and improve ethical standards.
Comparative evaluation of a new-generation HBsAg assay versus a conventional method in occult HBV infection and low-level HBsAg positivity
(Ankara Microbiology Society, 2026) Daşdemir, Ferhat Osman; Dinç, Harika Öykü; Sirekbasan, Serhat; Hamzeli, Nur; Alaçam, Sema; Karabulut, Nuran; Türk, Süreyya; Dereli, Nida; Akçin, Rüveyda; Kocazeybek, Bekir
This study aimed to comparatively evaluate the conventional hepatitis B surface antigen (HBsAg) assay and the next-generation HBsAg NEXT (HBsAgNx) assay in samples with low-level HBsAg positivity and in cases of occult hepatitis B infection (OBI). A total of 497 individuals were included in the study, comprising 300 individuals with low-level HBsAg positivity, 100 OBI cases (64 seropositive and 36 seronegative) and 97 healthy controls. Serum samples were analyzed using the Abbott ARCHITECT HBsAg Qualitative II assay (Abbott Diagnostics, Wiesbaden, Germany) and the Abbott Alinity i HBsAg NEXT assay (Abbott Diagnostics, Wiesbaden, Germany). The presence of HBV DNA was confirmed by real-time polymerase chain reaction (Rt-PCR) using the COBAS AmpliPrep/COBAS TaqMan HBV test v2.0 (Roche Diagnostics, Mannheim, Germany). HBV DNA (Rt-PCR) was accepted as the gold standard reference for diagnostic performance evaluation. To minimize potential bias arising from sample selection, individuals with low level HBsAg positivity and OBI cases were analyzed separately. In the low-level HBsAg-positive group, semi-quantitative S/CO values of the assays were compared, whereas in the OBI group, only the detection rates of HBV DNA–positive cases were evaluated. A total of 17 OBI cases (17%) were identified that were tested negative by the conventional assay but positive by the HBsAgNx assay. Differences between the assays were evaluated using the McNemar test and p< 0.05 was considered statistically significant. Median values obtained with the HBsAgNx assay were significantly higher than those obtained with the conventional assay (p< 0.001). The HBsAgNx assay provides clinically significant contributions particularly in the OBI group, by detecting cases that cannot be identified by conventional assays. These findings indicate that the integration of high-sensitivity HBsAg assays into current HBV diagnostic algorithms would increase case detection and contribute to both transfusion safety and the clinical management of OBI.

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