Activation of the alpha 7 nicotinic acetylcholine receptor by GTS-21 mitigates contrast nephropathy in a rat model.

INTRODUCTION: Contrast nephropathy (CN) is characterized by oxidative stress, vasoconstriction, tubular toxicity and hypoxia of the renal medulla. We aimed to test the therapeutic effects of an α7 nicotinic acetylcholine receptor (nAChR) agonist, GTS-21, in an experimental CN model. METHODS: Male Sprague‒Dawley rats (n=40) were divided into 4 groups: saline-treated control, GTS-21-treated control, contrast, and GTS-21-treated contrast groups. Starting on the 1st day, GTS-21 (4 mg/kg, intraperitoneally) or saline was administered twice a day for 3 days. CN was induced on the second day by intravenous injection of indomethacin (10 mg/kg), L-NAME (10 mg/kg), and a contrast agent with high osmolarity (6 ml/kg; Urografin 76%). At the 72nd hour, blood and kidney samples were obtained for the determination of biochemical, histological, and gene expression parameters. RESULTS: Compared to those in control rats, the elevated serum BUN level in the contrast group decreased with GTS-21 treatment, while H&E staining and TUNEL assays showed that contrast-induced renal injury was improved by GTS-21. Moreover, GTS-21 treatment in the CN also increased the antioxidant glutathione level. In the contrast group, a significant increase in IL-6 expression and a decrease in TGF-ß expression were observed; however, GTS-21 treatment decreased IL-6 expression and increased TGF-ß expression. CONCLUSION: GTS-21 significantly alleviated renal injury parameters through antioxidant, anti-inflammatory, and antiapoptotic mechanisms in the CN model.

Evaluation of the Diagnostic Value of Cell Population Data in Sepsis in Comparison to Localized Infection, Chronic Inflammation, and Noninfectious Inflammation Cases.

INTRODUCTION: Sepsis, defined as an increase of 2 points or more in the sequential organ failure assessment score, is a life-threatening organ dysfunction caused by the dysregulated host response to infection. Volume-conductivity-scatter (VCS) parameters of cell counters which are known as cell population data (CPD) have been suggested to be beneficial in diagnosing sepsis. We aimed to evaluate the diagnostic value of CPD parameters in sepsis in comparison to nonsystemic infection cases (NSI) and non-infectious acute and chronic inflammatory conditions. MATERIALS AND METHODS: We prospectively included four groups of patients" data: sepsis (n = 66), localized infection (pneumonia, n = 59), chronic inflammation (rheumatoid arthritis, n = 92) and noninfectious inflammation (coronary artery bypass graft operation, n = 56) groups, according to their clinical status and laboratory results. Samples for cell counting and serum markers were collected on the same day of culture collection. VCS parameters were measured by Unicel DxH800 Coulter Cellular Analyzer (Beckman Coulter, USA). RESULTS: Mean neutrophil volume (MN-V-NE), was highest in the sepsis group [155(149-168)] compared to the localized infection [148(140-158)], chronic inflammation [144.5(142-149)] and noninfectious inflammation [149(145.2-153.7)] (P = 0.001, P < 0.001, P < 0.001, respectively). Neutrophil volume SD (SD-V-NE) was higher in the sepsis [21(18.8-23.7)], significantly differentiating sepsis from other groups. The area under curves of procalcitonin and hs-C-reactive protein were 0.846 and 0.837, respectively, in the receiver-operating characteristic curves (ROC) . CPD combinations, (SD-V NE + SD-V LY + SD-V MO), (SD-V NE + SD-V MO), and (MN-V NE + SD-V NE + SD-C LY + SD-V MO) had greater AUC values than procalcitonin's. CONCLUSION: VCS parameters might be promising for differentiating sepsis and non-sepsis cases. Additionally, obtaining these data routinely makes their prospects promising without any additional cost and time.

Prevalence of Demodex folliculorum and Demodex brevis in patients with blepharitis and chalazion.

PURPOSE: Demodex folliculorum and Demodex brevis are common ectoparasites on skin that also can lead to blepharitis and chalazion. The aim of our study is to determine the prevalence of Demodex spp. in eyelashes of patients diagnosed with chronic blepharitis and chalazion. METHODS: This study included 330 patients diagnosed with chronic blepharitis, 70 patients diagnosed with chalazion and 130 volunteers without any ocular problems. Patient eyelashes were examined under a light microscope at magnifications of × 40, × 100 and × 400. Demodex spp. were determined. RESULTS: Parasite prevalence was significantly higher in blepharitis (75.5%) and chalazion groups (70%) compared to the control group (16.2%) (p < 0.001). The prevalence of D. folliculorum in the blepharitis group and D. brevis in the chalazion group was found to be significantly higher compared to other groups (p < 0.05). The average number of mites per eyelash was found to be significantly higher in patients with Demodex positive blepharitis (p = 0.001) and in chalazion patients (p = 0.047) than in the control group. It has been determined that mite positivity increases with age in blepharitis and control groups (p < 0.05). In the group with blepharitis, it was found that mite positivity was significant in the presence of symptoms (p = 0.0001) and Demodex positivity decreased as the education level of individuals increased (p = 0.039). CONCLUSION: The results of the study show that Demodex spp infestations should be considered in chronic blepharitis and chalazion.

Nesfatin-1 treatment preserves antioxidant status and attenuates renal fibrosis in rats with unilateral ureteral obstruction.

BACKGROUND: Nesfatin-1 (NES-1), an anorexigenic peptide, was reported to have anti-inflammatory and anti-apoptotic actions in several inflammation models. METHODS: To elucidate potential renoprotective effects of NES-1, unilateral ureteral obstruction (UUO) was induced in male Sprague Dawley rats by ligating left ureters. The rats were injected intraperitoneally with either saline (SL) or NES-1 (10 µg/kg/day) for 7 or 14 days (n = 8 in each group). On the 7th or 14th day, obstructed kidneys were removed for the isolation of leucocytes for flow-cytometric analysis and the assessments of biochemical and histopathological changes. RESULTS: Opposite to glutathione levels, renal myeloperoxidase activity in the SL-treated UUO group was significantly increased compared with the sham-operated group, while NES-1 treatment abolished the elevation. The percentages of CD8+/CD4+ T-lymphocytes infiltrating the obstructed kidneys were increased in the SL-treated groups but treatment with NES-1 did not prevent lymphocyte infiltration. Elevated tumour necrosis factor-alpha (TNF-α) levels in SL-treated UUO group were decreased with NES-1. Although total degeneration scores were similarly increased in all UUO groups, tubular dilatation scores were significantly increased in UUO groups and lowered by NES-1 only in the 7-day treated group. Elevated interstitial fibrosis scores in the SL-treated groups were decreased in both 7- and 14-day NES-1 treated groups, while alpha-smooth muscle actin (α-SMA) and apoptosis scores were depressed in both NES-1 treated groups. CONCLUSION: The present data demonstrate that UUO-induced renal fibrosis is ameliorated by NES-1, which appears to involve the inhibition of neutrophil infiltration and thereby amelioration of oxidative stress and inflammation. These data suggest that NES-1 may have a regulatory role in protecting the kidneys against obstruction-induced renal injury.

The Efficacy of Hydrodilatation for the Prevention of Vasospasm following Microsurgical Anastomosis.

BACKGROUND: Vasospasm is a major problem following microsurgical reconstruction which can result in the partial or complete loss of the flap tissue. The aim of this study was to investigate the efficiency of hydrodilatation for the prevention of vasospasm. METHODS: Thirty male Wistar rats were used for this experimental study. Femoral arteries of were exposed, photographed, and transected. In group 1, group 2, and group 3 papaverine solution, hydrodilatation, and minimal mechanical dilatation (control group) was performed, respectively. The anastomosis was completed and the arteries were photographed again 10 minutes after completion of the anastomosis. Following 7-day period samples for transmission electron microscopy (TEM) and light microscopy were obtained. RESULTS: The mean vessel diameters prior to transection were 0.43, 0.45, and 0.52 mm in the papaverine, hydrodilatation, and control groups, respectively. The mean vessel diameter 10 minutes following the completion of anastomosis was 0.76, 0.75, and 0.51 mm in the papaverine, hydrodilatation, and control groups, respectively. Median score for papaverine group regarding histological parameters of regular endothelial lining and lumen, neutrophil infiltration, vascular congestion, and edema in tunica adventitia was 2, 3, 2, and 3 positive, respectively. Median score for the papaverine group regarding histological parameters of regular endothelial lining and lumen, neutrophil infiltration, vascular congestion, and edema in tunica adventitia was 3, 3, 3, and 3 positive, respectively. All the histological scores were negative in the control group. The difference between the control group and the experiment groups 1 and 2 was significant regarding all four histological parameters (p < 0.05). CONCLUSION: Hydrodilatation and papaverine application were both effective in preventing vasospasm following microsurgical intervention but papaverine caused slightly less damage to the endothelial lining and less edema in the tunica adventitia when compared with the hydrodilatation. Hydrodilatation group showed a vasodilatory effect that was statistically similar to that of papaverine, which has a proven efficacy.

Association of Conductive Hearing Loss with the Structural Changes in the Organ of Corti.

OBJECTIVE: The aim of the study was to evaluate the association of conductive hearing loss (CHL) with the structural changes in the organ of Corti. METHODS: Twenty ears of 10 healthy adult Wistar albino rats were included in the study. The right ears (n = 10) of the animals served as controls (group 1), and no surgical intervention was performed in these ears. A tympanic membrane perforation without annulus removal was performed under operative microscope on the left ears (n = 5) in 5 of 10 animals (group 2). A tympanic membrane perforation with annulus removal was performed under operative microscope on the left ears (n = 5) of the remaining 5 animals (group 3). Auditory brainstem response testing was performed in the animals before the interventions. After 3 months, the animals were sacrificed, their temporal bones were removed, and inner ears were investigated using scanning electron microscopy (SEM). The organ of Corti was evaluated from the cochlear base to apex in the modiolar axis, and the parameters were scored semiquantitatively. RESULTS: In group 1, the pre- and post-intervention hearing thresholds were similar (p > 0.05). In group 2, a hearing decrease of at least 5 dB was encountered in all test frequencies (p > 0.05). In group 3, at the frequency range of 2-32 kHz, there was a significant hearing loss after 3 months (p < 0.01). After 3 months, the hearing thresholds in group 2 and 3 were higher than group 1 (p < 0.01). The hearing threshold in group 3 was higher than group 2 (p < 0.01). On SEM evaluation, the general cell morphology and stereocilia of the outer hair cells were preserved in all segments of the cochlea in group 1 with a mean SEM score of 0.2. There was segmental degeneration in the general cell morphology and outer hair cells in group 2 with a mean SEM score of 2.2. There was widespread degeneration in the general cell morphology and outer hair cells in group 3 with a mean SEM score of 3.2. The SEM scores of group 2 and 3 were significantly higher than group 1 (p < 0.05). The SEM scores of group 3 were significantly higher than group 2 (p < 0.05). CONCLUSION: CHL may be associated with an inner ear damage. The severity of damage appears to be associated with severity and duration of CHL. Early correction of CHL is advocated in order to reverse or prevent progression of the inner ear damage, which will enhance the success rates of hearing restoration surgeries. Subjective differences and compliance of the hearing aid users may be due to the impact of CHL on inner ear structures.

The Role of Extracellular Vesicles Secreted From Thermal Stress-Induced Adipose-Derived Stem Cells on Bone Regeneration.

PURPOSE: Extracellular vesicles (EVs) are responsible for intercellular communication. Mesenchymal stem cell-derived vesicles have been shown to have similar properties as functional mesenchymal stem cells. The aim of this study was to compare the therapeutic benefit of EVs obtained from adipose tissue-derived stem cells (ADSC) on bone repair whereas using ß-tricalcium phosphate (ß-TCP) biomaterial as a carrier. MATERIALS AND METHOD: A single critical size bone defect of 8 mm in diameter was created on the right side of rat calvarium using a custom-made punch needle. Animals were randomly divided into 5 groups: group 1 (no treatment), group 2 (bone graft), group 3 (ß-TCP + ADSC), group 4 (ß-TCP + EV), group 5 (ß-TCP). Eight weeks later, animals were sacrificed and histologic and radiologic evaluation was performed. RESULTS: Semiquantitative histologic scoring demonstrated significantly higher bone regeneration scores for groups 2, 3, and 4 compared to group 1. Radiologic imaging showed significantly higher bone mineral density for groups 2, 3, and 5 compared to group 1. There were no significant differences between treatment groups in either histologic or radiologic scoring. CONCLUSIONS: Our data showed that EVs provided from thermally induced ADSCs did not show any significant difference in bone regeneration when compared to ADSCs themselves. Future studies should focus on determining the optimum amount and content of EV application since these vary significantly depending on the microenvironment.

Acute dental pain elevates salivary oxytocin in women: a risk factor during pregnancy.

Irreversible pulpitis is an acute, brief, and painful condition. Oxytocin, cortisol, and secretory immunoglobulin A (sIgA) are released by the body in response to pain and emotional stress. The aim of this study was to investigate the expression of salivary cortisol, sIgA, and oxytocin among patients with irreversible pulpitis. This was an ethically approved case-control study comparing 90 cases of irreversible pulpitis and 40 healthy individuals. Five study groups were established: nonpregnant female pulpitis, pregnant female pulpitis, male pulpitis, healthy (nonpregnant) female control, and healthy male control. Pregnant women in the first trimester were enrolled in the study. Participants received both clinical and radiographic examinations, completed a simple questionnaire related to food intake, habits, and anxiety, and their pain levels were recorded on a visual analog scale in which 0 represented no pain and 10 represented the worst possible pain. Unstimulated saliva samples were collected to measure oxytocin, sIgA, and cortisol levels. Dental pulp specimens were obtained and stained with hematoxylin and eosin to evaluate the agreement between clinical and histologic pulpal diagnoses. The statistical analysis included analysis of variance and Tukey tests. The majority of patients (37%) recorded a score of 8 (severe pain) on the visual analog scale, while a score of 10 (worst possible pain) was recorded only by pregnant women (3%). There was no statistically significant difference among healthy subjects for all salivary samples. Oxytocin levels increased significantly in nonpregnant (P < 0.5) and pregnant (P < 0.001) women with pulpitis. Cortisol (P < 0.01) and sIgA (P < 0.001) levels were significantly elevated only in pregnant women with pulpitis. The results of the present study indicate that acute dental pain during pregnancy can be considered as a pregnancy risk factor because of the resulting elevated oxytocin and cortisol levels.

Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer.

Curcumin has a therapeutic potential activity through modulation of different signaling pathways in various types of cancer. However, the relationship between the efficacy of curcumin and the homologous recombination (HR) mechanism which plays important roles in the repair of double strand DNA (dsDNA) breaks remains uncertain. Herein, we explored curcumin-dependent dsDNA breaks and the association of curcumin with HR mechanism in triple negative breast cancer (TNBC). The cytotoxic and therapeutic activity of curcumin on HCC1937 (BRCA1 mutant), MDA-MB-231 (BRCA1 wild type) TNBC and HUVEC control cell lines were assessed. Then, the expression level and subcellular localization of H2AX, PARP1, BRCA1 and RAD51 were detected by RT-PCR and immunofluorescence analysis. Furthermore, ultrastructural changes of cell death were observed by TEM. Our findings for the first time demonstrated that curcumin's therapeutic activity was more pronounced in HCC1937 cells through the suppression of HR mechanism and the induction of dsDNA breaks. Consequently, curcumin based therapy could benefit in patients with TNBC particularly especially in women with a BRCA1 mutation.

Radiogenomics of lower-grade gliomas: machine learning-based MRI texture analysis for predicting 1p/19q codeletion status.

OBJECTIVE: To evaluate the potential value of the machine learning (ML)-based MRI texture analysis for predicting 1p/19q codeletion status of lower-grade gliomas (LGG), using various state-of-the-art ML algorithms. MATERIALS AND METHODS: For this retrospective study, 107 patients with LGG were included from a public database. Texture features were extracted from conventional T2-weighted and contrast-enhanced T1-weighted MRI images, using LIFEx software. Training and unseen validation splits were created using stratified 10-fold cross-validation technique along with minority over-sampling. Dimension reduction was done using collinearity analysis and feature selection (ReliefF). Classifications were done using adaptive boosting, k-nearest neighbours, naive Bayes, neural network, random forest, stochastic gradient descent, and support vector machine. Friedman test and pairwise post hoc analyses were used for comparison of classification performances based on the area under the curve (AUC). RESULTS: Overall, the predictive performance of the ML algorithms were statistically significantly different, χ2(6) = 26.7, p < 0.001. There was no statistically significant difference among the performance of the neural network, naive Bayes, support vector machine, random forest, and stochastic gradient descent, adjusted p > 0.05. The mean AUC and accuracy values of these five algorithms ranged from 0.769 to 0.869 and from 80.1 to 84%, respectively. The neural network had the highest mean rank with mean AUC and accuracy values of 0.869 and 83.8%, respectively. CONCLUSIONS: The ML-based MRI texture analysis might be a promising non-invasive technique for predicting the 1p/19q codeletion status of LGGs. Using this technique along with various ML algorithms, more than four-fifths of the LGGs can be correctly classified. KEY POINTS: • More than four-fifths of the lower-grade gliomas can be correctly classified with machine learning-based MRI texture analysis. Satisfying classification outcomes are not limited to a single algorithm. • A few-slice-based volumetric segmentation technique would be a valid approach, providing satisfactory predictive textural information and avoiding excessive segmentation duration in clinical practice. • Feature selection is sensitive to different patient data set samples so that each sampling leads to the selection of different feature subsets, which needs to be considered in future works.

Artificial Intelligence in Renal Mass Characterization: A Systematic Review of Methodologic Items Related to Modeling, Performance Evaluation, Clinical Utility, and Transparency.

OBJECTIVE. The objective of our study was to systematically review the literature about the application of artificial intelligence (AI) to renal mass characterization with a focus on the methodologic quality items. MATERIALS AND METHODS. A systematic literature search was conducted using PubMed to identify original research studies about the application of AI to renal mass characterization. Besides baseline study characteristics, a total of 15 methodologic quality items were extracted and evaluated on the basis of the following four main categories: modeling, performance evaluation, clinical utility, and transparency items. The qualitative synthesis was presented using descriptive statistics with an accompanying narrative. RESULTS. Thirty studies were included in this systematic review. Overall, the methodologic quality items were mostly favorable for modeling (63%) and performance evaluation (63%). Even so, the studies (57%) more frequently constructed their work on nonrobust features. Furthermore, only a few studies (10%) had a generalizability assessment with independent or external validation. The studies were mostly unsuccessful in terms of clinical utility evaluation (89%) and transparency (97%) items. For clinical utility, the interesting findings were lack of comparisons with both radiologists' evaluation (87%) and traditional models (70%) in most of the studies. For transparency, most studies (97%) did not share their data with the public. CONCLUSION. To bring AI-based renal mass characterization from research to practice, future studies need to improve modeling and performance evaluation strategies and pay attention to clinical utility and transparency issues.

Radiomics of Renal Masses: Systematic Review of Reproducibility and Validation Strategies.

OBJECTIVE. The purpose of this study was to systematically review the radiomics literature on renal mass characterization in terms of reproducibility and validation strategies. MATERIALS AND METHODS. With use of PubMed and Google Scholar, a systematic literature search was performed to identify original research papers assessing the value of radiomics in characterization of renal masses. The data items were extracted on the basis of three main categories: baseline study characteristics, radiomic feature reproducibility strategies, and statistical model validation strategies. RESULTS. After screening and application of the eligibility criteria, a total of 41 papers were included in the study. Almost one-half of the papers (19 [46%]) presented at least one reproducibility analysis. Segmentation variability (18 [44%]) was the main theme of the analyses, outnumbering image acquisition or processing (3 [7%]). No single paper considered slice selection bias. The most commonly used statistical tool for analysis was intraclass correlation coefficient (14 of 19 [74%]), with no consensus on the threshold or cutoff values. Approximately one-half of the papers (22 [54%]) used at least one validation method, with a predominance of internal validation techniques (20 [49%]). The most frequently used internal validation technique was k-fold cross-validation (12 [29%]). Independent or external validation was used in only three papers (7%). CONCLUSION. Workflow characteristics described in the radiomics literature about renal mass characterization are heterogeneous. To bring radiomics from a mere research area to clinical use, the field needs many more papers that consider the reproducibility of radiomic features and include independent or external validation in their workflow.

Machine learning-based unenhanced CT texture analysis for predicting BAP1 mutation status of clear cell renal cell carcinomas.

BACKGROUND: BRCA1-associated protein 1 (BAP1) mutation is an unfavorable factor for overall survival in patients with clear cell renal cell carcinoma (ccRCC). Radiomics literature about BAP1 mutation lacks papers that consider the reliability of texture features in their workflow. PURPOSE: Using texture features with a high inter-observer agreement, we aimed to develop and internally validate a machine learning-based radiomic model for predicting the BAP1 mutation status of ccRCCs. MATERIAL AND METHODS: For this retrospective study, 65 ccRCCs were included from a public database. Texture features were extracted from unenhanced computed tomography (CT) images, using two-dimensional manual segmentation. Dimension reduction was done in three steps: (i) inter-observer agreement analysis; (ii) collinearity analysis; and (iii) feature selection. The machine learning classifier was random forest. The model was validated using 10-fold nested cross-validation. The reference standard was the BAP1 mutation status. RESULTS: Out of 744 features, 468 had an excellent inter-observer agreement. After the collinearity analysis, the number of features decreased to 17. Finally, the wrapper-based algorithm selected six features. Using selected features, the random forest correctly classified 84.6% of the labelled slices regarding BAP1 mutation status with an area under the receiver operating characteristic curve of 0.897. For predicting ccRCCs with BAP1 mutation, the sensitivity, specificity, and precision were 90.4%, 78.8%, and 81%, respectively. For predicting ccRCCs without BAP1 mutation, the sensitivity, specificity, and precision were 78.8%, 90.4%, and 89.1%, respectively. CONCLUSION: Machine learning-based unenhanced CT texture analysis might be a potential method for predicting the BAP1 mutation status of ccRCCs.

Ultrastructural GABA immunogold labeling in the substantia nigra pars reticulata of kindled genetic absence epilepsy rats.

Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a well-known animal model of absence epilepsy and they are resistant to electrical kindling stimulations. The present study aimed to examine possible differences in gamma-aminobutyric acid (GABA) levels and synapse counts in the substantia nigra pars reticulata anterior (SNRa) and posterior (SNRp) regions between GAERS and Wistar rats receiving kindling stimulations. Animals in the kindling group either received six stimulations in the amygdala and had grade 2 seizures or they were kindled, having grade five seizures. Rats were decapitated one hour after the last stimulation. SNR regions were obtained after vibratome sectioning of the brain tissue. GABA immunoreactivity was detected by immunogold method and synapses were counted. Sections were observed by transmission electron microscope and analyzed by Image J program. GABA density in the SNRa region of fully kindled GAERS and Wistar groups increased significantly compared to that of their corresponding grade 2 groups. The number of synapses increased significantly in kindled and grade 2 GAERS groups, compared to kindled and grade 2 Wistar groups, respectively, in the SNRa region. GABA density in the SNRp region of kindled GAERS group increased significantly compared to that of GAERS grade 2 group. In the SNRp region, both kindled and grade 2 GAERS groups were found to have increased number of synapses compared to that of GAERS control group. We concluded that both SNRa and SNRp regions may be important in modulating resistance of GAERS to kindling stimulations.

Ultrastructural investigation of synaptic alterations in the rat hippocampus after irradiation and hyperthermia.

This study aimed to investigate ultrastructural synaptic alterations in rat hippocampus after in utero exposure to irradiation (IR) and postnatal exposure to hyperthermia (HT). There were four groups in each of the time points (3rd and 6th months). IR group: Pregnant rats were exposed to radiation on the 17th gestational day. HT group: Hyperthermia was applied to the rat pups on the 10th day after their birth. IR+HT group: Both IR and HT were applied at the same time periods. Control group: No IR or HT was applied. Rat pups were sacrificed after 3 and 6 months. Thin sections from the dentate gyrus (DG) and the CA3 of hippocampus were evaluated for synapse numbers by electron microscopy. Synapses were counted, and statistical analysis was performed. Abnormalities in myelin sheath, mossy terminals and neuropil were observed in the CA3 and DG of all groups. The synapses in the CA3 region were significantly increased in the IR-3rd month, IR-6th month, and IR+HT-3rd month groups vs control group. Synapses were significantly increased in the DG of HT-3rd month group. A trend for an increase in synapse numbers was seen in the CA3 and DG. Increased number of synapses in the rat hippocampus may be due to mossy fiber sprouting, possibly caused by in utero irradiation and/or postnatal hyperthermia.

Evaluation of clinical and demographic characteristics of Turkish and Syrian pediatric cutaneous leishmaniasis patients from Hatay, Turkey after the Syrian civil war.

INTRODUCTION: Cutaneous leishmaniasis (CL) is a skin disease affecting all ages but especially children. Cutaneous leishmaniasis exists in Turkey, and, especially together with emigration from Syria to Turkey in recent years due to the civil war in Syria, the incidence of the disease has increased. AIM: To investigate Syrian patients (SP) and Turkish patients (TP) in the pediatric age group who were diagnosed with CL and to compare the age, gender, clinical type, number of lesions, and lesion localizations of these patients. MATERIAL AND METHODS: We included CL patients aged 0-18 who were admitted to the outpatient clinic in the period 2015-2017 and in the first half of 2018. A total of 121 patients (SP, n = 87; TP, n = 34) were included in the study. RESULTS: The mean ages of TP and SP were 12.06 ±4.47 and 8.68 ±5.18 years and the disease durations were 6.25 ±3.86 and 4.73 ±3.39 months respectively (p = 0.049). The total number of lesions was 247. The mean lesion number per child was 2.35 ±2.28 in SP, and 1.23 ±0.55 in TP (p = 0.002). Two and multiple lesions were significantly higher in SP (p = 0.005). It was found that the lesions were most frequently located in the head/neck (HN) region (76.9%) and 44.1% of patients with HN localization belonged to the 7-12 age group. We also found that 57.1% of the HN lesions were of the papule type in the patients. CONCLUSIONS: We obtained similar results as in other studies in terms of age, gender, localization, and duration of lesions in general. When SP and TP were compared, we found that the number of lesions was higher, the disease duration was shorter, and the mean age was younger in SP.

The effects of antibiotics and melatonin on hepato-intestinal inflammation and gut microbial dysbiosis induced by a short-term high-fat diet consumption in rats.

High-fat diet (HFD) consumption leads to metabolic disorders, gastrointestinal dysfunction and intestinal dysbiosis. Antibiotics also disrupt the composition of intestinal microbiota. The aim of the present study was to investigate the impact of a short-term feeding with HFD on oxidative status, enteric microbiota, intestinal motility and the effects of antibiotics and/or melatonin treatments on diet-induced hepato-intestinal dysfunction and inflammation. Male Sprague-Dawley rats were pair-fed with either standard chow or HFD (45 % fat) and were given tap water or melatonin (4 mg/kg per d) or melatonin plus antibiotics (ABX; neomycin, ampicillin, metronidazole; each 1 g/l) in drinking water for 2 weeks. On the 14th day, colonic motility was measured and the next day intestinal transit was assessed using charcoal propagation. Trunk blood, liver and intestine samples were removed for biochemical and histopathological evaluations, and faeces were collected for microbiota analysis. A 2-week HFD feeding increased blood glucose level and perirenal fat weight, induced low-level hepatic and intestinal inflammation, delayed intestinal transit, led to deterioration of epithelial tight junctions and overgrowth of colonic bacteria. Melatonin intake in HFD-fed rats reduced ileal inflammation, colonic motility and perirenal fat accumulation. ABX abolished increases in fat accumulation and blood glucose, reduced ileal oxidative damage, suppressed HFD-induced overgrowth in colonic bacteria, and reversed HFD-induced delay in intestinal transit; however, hepatic neutrophil accumulation, hepatic injury and dysfunction were further enhanced. In conclusion, the results demonstrate that even a short-term HFD ingestion results in hepato-intestinal inflammatory state and alterations in bacterial populations, which may be worsened with antibiotic intake, but alleviated by melatonin.

Unenhanced CT Texture Analysis of Clear Cell Renal Cell Carcinomas: A Machine Learning-Based Study for Predicting Histopathologic Nuclear Grade.

OBJECTIVE. The purpose of this study is to investigate the predictive performance of machine learning (ML)-based unenhanced CT texture analysis in distinguishing low (grades I and II) and high (grades III and IV) nuclear grade clear cell renal cell carcinomas (RCCs). MATERIALS AND METHODS. For this retrospective study, 81 patients with clear cell RCC (56 high and 25 low nuclear grade) were included from a public database. Using 2D manual segmentation, 744 texture features were extracted from unenhanced CT images. Dimension reduction was done in three consecutive steps: reproducibility analysis by two radiologists, collinearity analysis, and feature selection. Models were created using artificial neural network (ANN) and binary logistic regression, with and without synthetic minority oversampling technique (SMOTE), and were validated using 10-fold cross-validation. The reference standard was histopathologic nuclear grade (low vs high). RESULTS. Dimension reduction steps yielded five texture features for the ANN and six for the logistic regression algorithm. None of clinical variables was selected. ANN alone and ANN with SMOTE correctly classified 81.5% and 70.5%, respectively, of clear cell RCCs, with AUC values of 0.714 and 0.702, respectively. The logistic regression algorithm alone and with SMOTE correctly classified 75.3% and 62.5%, respectively, of the tumors, with AUC values of 0.656 and 0.666, respectively. The ANN performed better than the logistic regression (p < 0.05). No statistically significant difference was present between the model performances created with and without SMOTE (p > 0.05). CONCLUSION. ML-based unenhanced CT texture analysis using ANN can be a promising noninvasive method in predicting the nuclear grade of clear cell RCCs.

Reliability of Single-Slice-Based 2D CT Texture Analysis of Renal Masses: Influence of Intra- and Interobserver Manual Segmentation Variability on Radiomic Feature Reproducibility.

OBJECTIVE. The objective of our study was to investigate the potential influence of intra- and interobserver manual segmentation variability on the reliability of single-slice-based 2D CT texture analysis of renal masses. MATERIALS AND METHODS. For this retrospective study, 30 patients with clear cell renal cell carcinoma were included from a public database. For intra- and interobserver analyses, three radiologists with varying degrees of experience segmented the tumors from unenhanced CT and corticomedullary phase contrast-enhanced CT (CECT) in different sessions. Each radiologist was blind to the image slices selected by other radiologists and him- or herself in the previous session. A total of 744 texture features were extracted from original, filtered, and transformed images. The intraclass correlation coefficient was used for reliability analysis. RESULTS. In the intraobserver analysis, the rates of features with good to excellent reliability were 84.4-92.2% for unenhanced CT and 85.5-93.1% for CECT. Considering the mean rates of unenhanced CT and CECT, having high experience resulted in better reliability rates in terms of the intraobserver analysis. In the interobserver analysis, the rates were 76.7% for unenhanced CT and 84.9% for CECT. The gray-level cooccurrence matrix and first-order feature groups yielded higher good to excellent reliability rates on both unenhanced CT and CECT. Filtered and transformed images resulted in more features with good to excellent reliability than the original images did on both unenhanced CT and CECT. CONCLUSION. Single-slice-based 2D CT texture analysis of renal masses is sensitive to intra- and interobserver manual segmentation variability. Therefore, it may lead to nonreproducible results in radiomic analysis unless a reliability analysis is considered in the workflow.

Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats.

The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 µg/mL/d), alendronate (70 µg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 µg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin- or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate- or melatonin-treated groups. Oxidative gastric damage was increased in saline- or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use. HIGHLIGHTS: Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.