"Predicting diabetic kidney disease in youth with type 1 diabetes: Insights from genetic risk assessment".

OBJECTIVE: Diabetic kidney disease (DKD) is influenced by multiple factors, yet its precise progression mechanisms remain largely unclear. This study aimed to create a clinical risk-scoring system based on genetic polymorphisms in the AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, and ZMIZ1 genes. METHODS: The study included a DKD group diagnosed with diabetic kidney disease before age 18 and a WDC group matched by age, gender, and age at diabetes diagnosis. Genetic data and clinical data from diabetes diagnosis to moderately increased albuminuria (MIA) detection were compared between the groups. RESULTS: Among 43 DKD cases, 22 were girls and 21 were boys. At MIA diagnosis, mean body weight SDS was -0.24 ± 0.94, height SDS was 0.34 ± 1.15, and BMI SDS was -0.26 ± 0.94. Systolic blood pressure was at the 72nd percentile (2-99), and diastolic blood pressure was at the 74th percentile (33-99). Significant differences in rs267734, rs267738, and rs942263 polymorphisms were found between DKD and non-complication diabetic groups (13[30.2 %] vs 5[11.6 %], p = 0.034; 14[32.6 %] vs 5[11.6 %], p = 0.019; 26[60.5 %] vs 40[93 %], p < 0.001). CONCLUSION: Several factors were identified as significant in DKD onset, including low follow-up weight SDS, elevated diastolic blood pressure, presence of rs267734, and absence of rs942263 polymorphisms. The model demonstrated a specificity of 81.4 % and a sensitivity of 74.4 %.

Effects of apelin on neonatal brain neurogenesis in L-NAME-induced maternal preeclampsia.

The aim of this study was to investigate the possible protective effects of apelin, which is known to have antioxidant and anti-inflammatory effects, on changes in neurogenesis in newborns of pregnant rats with L-NAME-induced preeclampsia. Wistar albino female rats were divided into four experimental groups: Control, Apelin, Preeclampsia and Preeclampsia + Apelin. Blood pressure was measured on the 5th, 11th and 17th days of gestation, urine protein was analyzed from urine samples collected for 24 h on the 6th, 12th and 18th days and serum creatinine was analyzed from serum samples. Maternal kidney and placenta tissues were obtained to establish the preeclampsia model, and neonatal brain tissues including the cortex, hippocampus and cerebellum regions were obtained to investigate neurogenesis and examined by histological and immunohistochemical methods. The number of newborns, body weight and brain weight of the newborns were measured. eNOS, IL-10, nNOS and NO levels in the brain analyzed via ELISA. Mean arterial pressure, urine protein and serum creatinine increased in the preeclampsia. Newborn weight decreased in the Preeclampsia group, the values in the Preeclampsia + Apelin group were closer to the Control and Apelin groups. In the Preeclampsia group, edema and dilatation in the proximal and distal tubules of kidneys, perivillous fibrin deposition and increase in syncytial nodules of placenta were observed. VEGF immunoreactivity decreased and iNOS immunoreactivity increased in both kidney and placenta. In neonatal brain tissue examinations, cytotoxic edema accompanied by thinning of cortex, delayed migration and lower cell counts in the hippocampus, and increase in intercellular spaces and EGL thickening in the cerebellum were observed in the preeclampsia. Expression of NeuN, GFAP, MBP, IL-10, eNOS, nNOS and NO levels decreased, whereas expression of Iba-1 increased in the preeclampsia. In the Preeclampsia + Apelin group, these findings were similar to the Control and Apelin groups. Apelin administration was found to be beneficial for preventing the adverse consequences of preeclampsia, but further experimental and clinical studies are needed to better understand these effects.

Gingival crevicular fluid levels of TLR-9, AIM-2, and ZBP-1 in periodontal diseases.

OBJECTIVES: Toll-like receptor (TLR)-9, may play a role in periodontal disease inflammation. This study measured TLR-9 and its related molecules, absence in melanoma-2 (AIM-2) and Z-DNA-binding protein-1 (ZBP-1), in gingival crevicular fluid (GCF) from patients with varying stages of periodontal disease to assess the role of pathogen-derived nucleic acids in inflammation. MATERIALS AND METHODS: The study comprised 80 participants: 20 with Stage III Grade C periodontitis, 20 with Stage III Grade B periodontitis (P-Stage III-B), 19 with gingivitis, and 21 with periodontal health. Parameters including probing depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP) were recorded. ELISA was used to analyze TLR-9, AIM-2, and ZBP-1 levels in GCF. Nonparametric tests were used for statistical comparisons. RESULTS: The total amount of TLR-9 was higher in P-Stage III-B than in the healthy group (p < 0.05). Similarly, the gingivitis group exhibited elevated GCF TLR-9 levels compared to the healthy group (p < 0.05). GCF AIM-2 and ZBP-1 levels remained consistent across groups (p > 0.05). Significant correlations were found between GCF TLR-9 and CAL (p < 0.05), BOP (p < 0.05), PI (p < 0.01), and GCF volume (p < 0.001). CONCLUSION: These findings suggested that the TLR-9-mediated inflammatory process plays a role in periodontal disease, as evidenced by the increased levels of TLR-9 in GCF.

Gingival phenotype classification by visual and probe visibility assessments: Relationship with thickness and probe design.

BACKGROUND: This study investigated the agreement among dentists in classifying gingival phenotype (GP) through periodontal probe visibility (PPV) assessment with various probe types and the visual method. Additionally, the relationship between GP classifications and gingival thickness (GT) was evaluated. METHODS: Photographs were taken with standard periodontal probe (SPP), color-coded periodontal probe (CCPP) tips in white, green, and blue, as well as metal phenotype probe (MPP) tips in gray and black. Evaluators (periodontist, periodontics resident, endodontics resident, dental student) assessed the photographs and classified the GPs. GT was measured by trans gingival probing. RESULTS: Visual method showed poor to fair agreement to classify GP. The lowest agreement regarding PPV was noted with white-tipped CCPP. The highest agreement in singular PPV was observed with CCPP blue (κ = 0.932), followed by CCPP green (κ = 0.791), MPP black (κ = 0.783), SPP (κ = 0.730), and MPP gray (κ = 0.690). Combined PPV data revealed fair to moderate agreement with CCPP and moderate to substantial agreement with MPP in GP classification. The corresponding GT to different GP classifications based on combined PPV were comparable. The agreement between SPP and CCPP in classifying non-thin phenotypes was 89.8%, while the agreement between SPP and MPP was 75.4%. Based on PPV, no significant GT cutoff value was found to distinguish between thin and non-thin phenotypes. CONCLUSION: Determining a precise GT that guarantees the visibility of a given probe can be difficult when evaluating GP. Regardless of the type of probe, the PPV method has a high potential for misclassifying GP, despite having an acceptable agreement. PLAIN LANGUAGE SUMMARY: Gingival phenotype (GP) is constituted by thickness of the gums and width of keratinized tissue around teeth. Direct visual evaluation or evaluating a periodontal probe's visibility beneath gums are established techniques to classify gingival phenotype. This study investigated how dentists classify GP using visual assessments and different types of periodontal probes, while also exploring the relationship between GP classifications and gingival thickness. Results showed varied agreement among dentists in classifying GP, with lower agreement observed when using certain types of probes, notably the white-tipped phenotype probe. The highest agreement was found with the blue phenotype probe. Data from periodontal probe visibility assessments indicated fair to moderate agreement with certain probes, suggesting some inconsistency in classification methods. Interestingly, GP classification with visual assessments or probes did not correlate with gingival thickness, which may highlight the importance of considering both factors in clinical practice. These findings underline the need for attention when relying solely on visual assessments or specific probe types for accurate GP classification.

Protective effects of E-CG-01 (3,4-lacto cycloastragenol) against bleomycin-induced lung fibrosis in C57BL/6 mice.

Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell aging is oxidative stress and it is known to have a role in idiopathic pulmonary fibrosis. In this paper, the protective effect of the E-CG-01 (3,4-lacto-cycloastragenol) molecule in terms of its antioxidant properties was evaluated in the bleomycin induced mice lung fibrosis model. Bleomycin sulfate was administered as a single dose (2.5 U/kg body weight) intratracheally to induce lung fibrosis. E-CG-01 was administered intraperitoneally in three different doses (2 mg/kg/day, 6 mg/kg/day, and 10 mg/kg/day) for 14 days, starting three days before the bleomycin administration. Fibrosis was examined by Hematoxylin-Eosin, Masson Trichrome, and immunohistochemical staining for TGF-beta1, Type I collagen Ki-67, and gama-H2AX markers. Activity analysis of catalase and Superoxide dismutase enzymes, measurement of total oxidant, total glutathione, and Malondialdehyde levels. In histological analysis, it was determined that all three different doses of the molecule provided a prophylactic effect against the progression of fibrosis compared to the bleomycin control group. However, it was observed that only the molecule applied in the high dose decreased the total oxidant stress level. Lung weight ratio increased in the BLM group but significantly reduced with high-dose E-CG-01. E-CG-01 at all doses reduced collagen deposition, TGF-ß expression, and Ki-67 expression compared to the BLM group. Intermediate and high doses of E-CG-01 also significantly reduced alveolar wall thickness and edema formation. These findings suggest that E-CG-01 has potential therapeutic effects in mitigating lung fibrosis through its antioxidant properties.

Salivary inflammatory burden in pre- and postmenopausal women: Associations with body mass index, patient-reported health, serum cytokines, and periodontal parameters.

BACKGROUND: The decline of estrogen levels during menopause impacts weight, mood, and overall health, both orally and systemically. This study assessed salivary levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-10, and IL-7 in postmenopausal (PMW) and regularly menstruating premenopausal (RMPW) women, while considering serum cytokine levels, body mass index (BMI), periodontal health, and self-reported physical and emotional well-being. METHODS: In this study, 75 PMW and 71 RMPW were included. Clinical and periodontal parameters were evaluated, and perceived health was assessed with the Women's Health Questionnaire (WHQ). Cytokine levels in both saliva and serum were quantified by enzyme-linked immunosorbent assay (ELISA). Covariate evaluations of salivary cytokines were conducted using hierarchical linear regression modeling. RESULTS: Cytokines were detectable in saliva from 71 PMW and 67 RMPW. In the initial unadjusted model, IL-7, IL-10, and TNF-α exibited significant differences between RMPW and PMW. However, these differences became non-significant (p > 0.05) in the final model after adjusting for age, which implies a negligible effect of the investigated covariates on salivary cytokine levels when age was considered. Lower levels of IL-6 in PMW, which initially showed no significant difference, became borderline (p = 0.054) in the final model after adjusting for age. CONCLUSIONS: After adjusting for multiple factors, no significant difference was found in the salivary levels of the investigated cytokines between RMPW and PMW. Factors such as BMI, perceived health, serum cytokine levels, and periodontal parameters seem to minimally influence these levels in PMW. However, age may be a stronger confounding factor.

Psychosocial Effects of the Pandemic on MS Patients at a University Hospital Following Patients with Telemedicine, Cross-sectional Study.

Introduction: The psychosocial effect of the pandemic on people with a disease such as multiple sclerosis (MS) that can cause disability and which medications that affect the immune system are used in treatment should be evaluated by physicians. We aimed to determine the psychosocial effects of the pandemic on MS patients and to evaluate the working and treatment continuation status, compliance with pandemic rules, and their perceptions regarding coronavirus disease 2019 (COVID-19). Methods: This study was designed as a cross-sectional and descriptive survey study. A total of 315 MS patients' demographic data, comorbidities, and degrees of disability, Beck Depression Inventory (BDI), Coronavirus Anxiety Scale (CAS), and compliance scores with pandemic restrictions were evaluated. Results: In the first period of the pandemic, approximately one-third of the patients were found to have major depression, and approximately 10% to have COVID anxiety. Both COVID anxiety and BDI scores were significantly higher in patients with symptoms suggestive of an attack during the pandemic process (p:0.0001 and p:0.002). CAS was higher in those who had a COVID-19 contact (p:0.045). BDI scores were significantly higher (respectively p:0.034, p:0.006, p:0.0001) in married/cohabiting patients, in patients who went on unpaid leave or lost their job, and in patients who described worsening of their previous MS-related complaints. Conclusion: Although the pandemic negatively affects the psychosocial status of MS patients, this effect can be reduced by identifying the groups that may be affected via telemedicine and taking necessary interventions.

Value of gingival crevicular fluid TREM-1, PGLYRP1, and IL-1ß levels during menopause.

OBJECTIVE: This study aimed to investigate the association of GCF TREM-1, PGLYRP1, and IL-1ß levels with periodontal health in pre- and postmenopausal women. BACKGROUND: Triggering receptor expressed on myeloid cells 1 (TREM-1), activated through its ligand peptidoglycan recognition protein 1 (PGLYRP1), stimulates proinflammatory cytokine production, such as interleukin (IL)-1ß, during periodontal inflammation. Postmenopausal changes may modulate these immune-inflammatory functions. No clinical study has yet investigated the effect of menopause on TREM-1, PGLYRP1, and IL-1ß levels in gingival crevicular fluid (GCF). METHODS: This cross-sectional study included 148 women (age range = 35-65 years), divided into postmenopausal women (PMW) (n = 76, mean age = 54 ± 5 years) and regularly menstruating premenopausal women (RMPW) (n = 72, mean age = 40 ± 4 years). Clinical periodontal parameters were recorded. TREM-1, PGLYRP1, and IL-1ß levels were quantified with enzyme-linked immunosorbent assays. Pearson's Chi-squared test and Mann-Whitney-U test were used to compare categorical and numerical variables, respectively. Spearman's Rho correlation analysis was used to test the linear relationship between variables. Analyte level data were categorized based on the periodontal diagnosis and menopause status (2 × 2 nonparametric factorial ANOVA). RESULTS: No significant differences in TREM-1, PGLYRP1, and IL-1ß levels between PMW and RMPW were observed (p > .05). Mean values of periodontal indexes including probing depth did not differ significantly between PMW and RMPW groups (p = .474). TREM-1 levels were significantly higher in both PMW and RMPW with periodontitis, compared to gingivitis or health (p = .0021). CONCLUSION: Menopause-related changes have no observable effect on GCF levels of TREM-1, PGLYRP1, and IL-1ß. Higher GCF TREM-1 levels in women with periodontitis regardless of their menopausal status indicate that TREM-1 may be an indicator for periodontitis both in premenopausal and postmenopausal women.

The solubility, pH value, chemical structure, radiopacity, and cytotoxicity of four different root canal sealers: an in vitro study.

OBJECTIVE: The aim of this study was to investigate solubility, pH value, chemical structure, radiopacity, and cytotoxicity of AH Plus BC, TotalFill BC, AH Plus, and AH Plus Jet sealers. MATERIALS AND METHODS: Cytotoxicity analysis with direct and extraction tests at 3 different concentrations (1:1, 1:2, 1:4 v/v%) and time (24 h, 48 h, and 72 h) on Saos-2, PdLF, and THP-1 cell lines, chemical structure with scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analysis, solubility, pH, and radiopacity values of AH Plus BC, TotalFill BC, AH Plus, and AH Plus Jet were evaluated. For statistical analyses of the groups, repeated measures, factorial, and one-way ANOVA tests were used. The statistical significance level was set at p < .05. RESULTS: Resin-based sealers showed higher cytotoxicity values than the bioceramic-based sealers (p < 0.05). Time and concentrations were effective on the cell viabilities for cell lines. Higher peaks of calcium were detected bioceramic-based sealers and higher amount of zirconium was detected in AH Plus BC (p < 0.05). AH Plus BC showed similar radiopacity value with AH Plus, AH Plus Jet, whereas TotalFill BC showed the lowest radiopacity (p < 0.05). Bioceramic-based sealers had higher pH values in all experiment periods, and the difference between resin- and bioceramic-based sealer groups was significant (p < 0.05). However, the solubility values of the tested root canal sealers revealed no differences (p > 0.05). CONCLUSIONS: The newly produced AH Plus BC Sealer showed similar properties with TotalFill BC, and their biological properties were better than AH Plus and AH Plus Jet. CLINICAL RELEVANCE: AH Plus BC could be a possible alternative to other bioceramic- or resin-based sealers.

Identification of Normal Fornix Depth Dataset Generated with a Validated Fornix Meter in Healthy Turkish Population.

PURPOSE: To provide an age and sex-classified reference dataset for normal fornix depth by measuring the lower and upper conjunctival fornix depth (FD) in healthy volunteers. METHODS: An epidemiological, prospective, cross-sectional study evaluates conjunctival FDs in 301 healthy Turkish volunteers aged 20-83. Fornix measurements were made using a validated fornix depth measurer (FDM). RESULTS: The mean age was 49.2 ± 19 in males and 48.6 ± 16.2 in females. The mean upper and lower conjunctival FDs were 15.9 (12-21) mm and 10.1 (6-13) mm, respectively. The mean upper and lower FDs were 15.4 (13-20) mm and 9.7 (6-13) mm in females, and 16.3 (12-21) mm and 10.5 (8-13) mm in males, respectively. . CONCLUSION: When the normative dataset created in healthy Turkish volunteers, it was observed that both the upper and lower FDs were shallower in females and that they gradually became shallower with age. Accordingly, when an evaluation for conjunctival pathology is to be made, the expected normal FD value for both age and sex should be considered.

Gingival crevicular fluid periodontal ligament-associated protein-1, sclerostin, and tumor necrosis factor-alpha levels in periodontitis.

BACKGROUND: In periodontitis, the equilibrium between bone formation and resorption skews in favor of bone loss. Periodontal ligament-associated protein-1 (PLAP-1) and sclerostin play a significant role in the suppression of bone formation. Tumor necrosis factor-alpha (TNF-α) is a central proinflammatory cytokine related to periodontal bone loss. This study aims to assess gingival crevicular fluid (GCF) PLAP-1, sclerostin, and TNF-α levels in individuals with periodontal disease. METHODS: Seventy-one individuals diagnosed with generalized stage III grade C periodontitis (n = 23), gingivitis (n = 24), and periodontal health (n = 24) were included in the study. Full-mouth clinical periodontal measurements were performed. PLAP-1, sclerostin, and TNF-α total amounts in GCF were quantified by ELISA. Nonparametric methods were used for the data analyses. RESULTS: Periodontitis group exhibited significantly higher GCF PLAP-1, sclerostin and TNF-α levels compared with gingivitis and periodontally healthy groups (p < 0.05). GCF PLAP-1 and TNF-α levels of gingivitis group were higher than healthy controls (p < 0.05) whereas GCF sclerostin levels were similar in two groups (p > 0.05). Significant positive correlations were found between GCF PLAP-1, sclerostin and TNF-α levels and all clinical parameters (p < 0.01). CONCLUSIONS: To our knowledge, this is the first study showing GCF PLAP-1 levels in periodontal health and disease. Increased GCF PLAP-1 and sclerostin levels and their correlations with TNF-α in periodontitis imply that those molecules might be involved in the pathogenesis of periodontal disease. Further studies in larger mixed cohorts are needed to enlighten the possible role of PLAP-1 and sclerostin in periodontal bone loss.

Gingival crevicular fluid galectin-3 and interleukin-1 beta levels in stage 3 periodontitis with grade B and C.

OBJECTIVES: This study aims to evaluate GCF Galectin-3 and Interleukin-1 beta (IL-ß) levels in different grades (B and C) of stage 3 periodontitis, concurrently, and also to investigate their discriminative efficiencies in periodontal diseases. MATERIALS AND METHODS: A total of 80 systemically healthy and non-smoker individuals, 20 stage 3 grade C (S3GC) periodontitis 20 stage 3 grade B (S3GB) periodontitis, 20 gingivitis, and 20 periodontally healthy were enrolled. Clinical periodontal parameters were recorded and GCF Galectin-3 and IL-1ß total amounts were measured by ELISA. Receiver operating characteristics curve was used for estimating the area under the curve (AUC). RESULTS: Galectin-3 and IL-1ß were detected in all participants. Both periodontitis groups had significantly higher GCF Galectin-3 total amounts than periodontally healthy controls (p <0.05). S3GC periodontitis group had also significantly higher GCF Galectin-3 levels than gingivitis group (p <0.05). GCF IL-1ß levels in periodontitis groups were higher than gingivitis and periodontally healthy groups (p <0.05). Galectin-3 exhibited an AUC value of 0.89 with 95% sensitivity to discriminate S3GC periodontitis from periodontal health, an AUC value of 0.87 with 80% sensitivity to discriminate S3GC periodontitis versus gingivitis, while an AUC value of 0.85 with 95% sensitivity to discriminate S3GB periodontitis from healthy controls. CONCLUSIONS: GCF Galectin-3 levels are involved in the pathogenesis of periodontal diseases. Galectin-3 showed excellent diagnostic performances to discriminate S3GB and S3GC periodontitis from periodontal health and gingivitis. CLINICAL RELEVANCE: The present findings suggest that GCF Galectin-3 levels may be useful in the diagnosis of the periodontal diseases.

Psychometric tests, critical flicker frequency, and inflammatory indicators in covert hepatic encephalopathy diagnosis.

Background and Aim: Hepatic encephalopathy (HE) is a frequent complication of liver diseases. Systemic inflammation is key for HE pathogenesis. The main goal of the study was to investigate the role of psychometric tests, critical flicker frequency (CFF), and comparative evaluation of inflammatory indicators for the diagnosis of covert HE (CHE). Materials and Methods: The study was a prospective, nonrandomized, case-control study with a total of 76 cirrhotic patients and 30 healthy volunteers. The West Haven criteria were used to determine the occurrence of CHE in cirrhotic patients. Psychometric tests were applied to healthy and cirrhotic groups. CFF, venous ammonia, serum endotoxin, IL-6, IL-18, tumor necrosis factor alpha (TNF-α) levels, and hemogram parameters were evaluated for cirrhotic patients. Results: CFF values and psychometric tests were found to accurately discriminate CHE positives from CHE negatives (p<0.05). When the control group was excluded, the digit symbol test and the number connection A test failed, unlike CFF and other psychometric tests. Using CFF, a 45 Hz cutoff value had 74% specificity and 75% sensitivity. Basal albumin levels (p=0.063), lymphocyte-to-monocyte ratio (LMR) (p=0.086), and neutrophil-to-lymphocyte ratio (p 0.052) were significant, albeit slightly, among CHE groups. Basal albumin levels had 50% sensitivity and 71% specificity when 2.8 g/dL was used as a cutoff value to determine CHE. Conclusion: Both psychometric tests and CFF can be useful in diagnosing CHE. Using cytokine and endotoxin levels seems to be inadequate to diagnose CHE. Using LMR and albumin levels instead of psychometric tests for diagnosing CHE can be promising.

Fluvastatin alleviates doxorubicin-induced cardiac and renal toxicity in rats via regulation of oxidative stress, inflammation, and apoptosis associated genes expressions.

Doxorubicin (DOXO) is a cytostatic agent used in the chemotherapy protocol of several cancers for more than 40 years, but usage of this drug in cancer treatment has been limited due to severe renal and cardiac tissue toxicities that may result in death in patients. Fluvastatin (FV) is a fully synthetic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor used as a cholesterol-lowering agent in patients with hypercholesterolemia. Previous studies revealed that FV also exhibits antioxidant, anti-inflammatory, and antitumor activity. Additionally, our previous study indicated that FV exerts a prophylactic effect on DOXO-induced testicular toxicity by preventing lipid peroxidation, supporting the antioxidant system, and regulating the blood-testis barrier-associated genes expression. Herein, we purposed to evaluate the possible therapeutic and the protective effects of FV on the DOXO-induced cardiac and renal toxicitiy model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction (real-time PCR) analyses. Results point out protective use of FV exerts a beneficial effect by repressing lipid peroxidation and by regulating the inducible nitric oxide synthase (iNOS), nitric oxide synthase endothelial (eNOS), nuclear factor kappa-B (NF-κB), and Caspase-3 (Casp3) protein and mRNA expressions, which play an important role in mediating DOXO-induced renal and cardiac toxicity mechanisms. In conclusion, FV may be a candidate agent for the prevention of renal and cardiac toxicities in cancer patients receiving DOXO chemotherapy.

Salivary secretory leukocyte protease inhibitor levels in patients with stage 3 grade C periodontitis: a comparative cross-sectional study.

Secretory leukocyte protease inhibitor (SLPI) is an anti-protease that protects mucosal tissue integrity owing to its anti-microbial and immunomodulatory properties. This study aimed to investigate SLPI levels in periodontal diseases, and analyze the potential correlation with clinical periodontal parameters. Whole saliva samples were obtained from healthy (n = 24), gingivitis (n = 24) and patients with stage 3 grade C periodontitis (n = 24). SLPI was measured by ELISA and normalized by total protein. Receiver operating characteristics (ROC) curve was used for estimating the area under the curve (AUC). The normalized SLPI levels were significantly reduced in periodontitis compared with gingivitis (4.84-fold) or health (1.83-fold) and negatively correlated with periodontal parameters. The ROC curves showed a good predictor value of the SLPI for differentiation of periodontitis versus health or gingivitis (AUC ≥ 0.80). This study demonstrates that the levels of SLPI are high in periodontal health, further elevated in gingivitis, but eventually decreased in severe periodontitis beyond the former two states. This observation may have broader implications in the context of inflammatory diseases affecting the oral mucosa, as it shows that the bacterial burden is disturbing the homeostatic balances of anti-microbial and anti-protease factors in the oral cavity.

Effect of interval between neoadjuvant chemoradiotherapy and surgery on disease recurrence and survival in rectal cancer: long-term results of a randomized clinical trial.

BACKGROUND: The optimal timing of surgery following chemoradiotherapy (CRT) is controversial. This trial aimed to assess disease recurrence and survival rates between patients with locally advanced rectal adenocarcinoma (LARC) who underwent total mesorectal excision (TME) after a waiting interval of 8 weeks or less (classic interval; CI) versus more than 8 weeks (long interval; LI) following preoperative CRT. METHODS: This was a phase III, single-centre, randomized clinical trial. Patients with LARC situated within 12 cm of the anal verge (T3-T4 or N+ disease) were randomized to undergo TME within or after 8 weeks after CRT. RESULTS: Between January 2006 and January 2017, 350 patients were randomized, 175 to each group. As of February 2022, the median follow-up time was 80 (6-174) months. Among the 322 included patients (CI, 159; LI, 163) the cumulative incidence of locoregional recurrence at 5 years was 10.1 per cent in the CI group and 6.9 per cent in the LI group (P = 0.143). The cumulative incidence of distant metastasis at 5 years was 30.8 per cent in the CI group and 18.6 per cent in the LI group (sub-HR = 1.78; 95 per cent c.i. 1.14 to 2.78, P = 0.010). The disease-free survival (DFS) in each group was 59.7 and 69.9 per cent respectively (P = 0.157), and overall survival (OS) rates at 5 years were 73.6 versus 77.9 per cent (P = 0.476). CONCLUSION: Incidence of distant metastasis decreased with an interval between CRT and surgery exceeding 8 weeks, but this did not impact on DFS or OS. REGISTRATION NUMBER: NCT03287843 (http://www.clinicaltrials.gov).

The Influence of the Intraductal Carcinoma of the Prostate on the Short-Term Oncological Outcomes.

AIM: The presence of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens correlates with adverse prognostic factors such as worse biochemical recurrence-free survival, higher grade and stage disease. This study aimed to investigate the effect of IDC-P in radical prostatectomy specimens on short-term oncological outcomes. MATERIALS AND METHODS: Patients who underwent RP at our clinic for prostate cancer between May 2016 and November 2019 were included in the study. They were divided into two groups based on the presence of IDC-P in RP specimens. Their clinical, pathological, and oncologic data were evaluated retrospectively. RESULTS: A total of 98 patients underwent RP with a mean age of 65.5 years (50-83) and a mean follow-up time of 31.2 months (6-52). Seventy and 28 patients were evaluated in the group without IDC-P and group with IDC-P, respectively. Surgical margin positivity (p=0.307) and lymph node metastasis (p=0.017) rates were higher in the group with IDC-P. Although there were no statistical differences between the groups, at follow-up biochemical recurrence rate (p=0.052) was higher, and mean time to biochemical recurrence rates were lower (p=0.057) in the group with IDC-P. The group with IDC-P was associated with a 3-fold increase in prostate cancer-specific mortality to the group without IDC-P (p=0.037). CONCLUSIONS: Patients with IDC-P at RP specimens have more advanced disease, shorter biochemical recurrence-free, and cancerspecific survival than those without IDC-P. Defining the presence of IDC-P in RP specimens is critical in choosing the appropriate treatment strategy and predicting the prognosis.

"Double hit" strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells.

Cancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44+/CD24-/low breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.

A transcranial magnetic stimulation study for the characterization of corticospinal pathway plasticity in children with neurological disorders.

We aimed to investigate cortical and radicular TMS-evoked motor evoked potentials (MEPs) in children with neurological disorders (n = 57, mean age: 5.45 years) and agematched healthy controls (n = 46). Four TMS parameters were analyzed: MEP amplitudes, the latencies of MEP, the latency jump (cortical MEP latency at rest - cortical active-MEP latency at with slightly contracted targeted muscle), and central motor conduction time. Children with neurological disorders were categorized according to the two major types of neuronal plasticity; excessive plasticity: 29 children with cerebral palsy and impaired plasticity: 28 children with neurodegenerative diseases, stroke, and central nervous system infections. The active-MEP abnormalities (absent and prolonged latencies) were correlated with the location of cortical involvement on MRI patterns. We obtained a significantly increased rate of abnormal cortical active-MEPs in children with impaired plasticity (21/28, 75%) compared with excessive plasticity (18/29, 62%). The rate of absent MEP response is three times more in children with impaired plasticity (43%) than in children with excessive plasticity (14%). A more reduced latency jump was measured in children with impaired plasticity compared to children with excessive plasticity. TMS-evoked active-MEPs and latency jumping are valuable parameters for characterizing neuronal plasticity in children with neurological disorders.

The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS. METHODS AND RESULTS: Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05). CONCLUSIONS: In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.