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Background: Autophagy is a catabolic process whereby organelles and long-lived proteins are recycled through lysosomes to maintain cellular homeostasis. This process is being widely studied using culture techniques and animal models; however, cervicovaginal smears have not been used to detect autophagy. Aims: Our study aims to detect and evaluate autophagy in normal, malignant, infectious, and atypical cells in cervicovaginal smears by using cytological and immunocytochemical methods. Materials and Methods: Papanicolaou-stained 200 cervicovaginal smears were examined and 55 of 200 (27.5%) smears containing negative for intraepithelial lesion or malignancy (NILM) with identifiable infections and/or reactive/reparative changes (INF); briefly, NILM-INF (n = 31, 56.4%), atypical (n = 4, 7.3%), and malignant cells (n = 20, 36.3%) were evaluated as a study group. One hundred forty-five of 200 (72.5%) normal smears were accepted as the NILM without any identifiable infections (control group). The autophagy marker protein Microtubule-associated protein 1 light chain 3 A (MAP1LC3A) was used for immunocytochemical examination. Results: The staining intensity of the MAP1LC3A protein and autophagy positivity were lower in the malignant cells; however, they were higher in the NILM-INF and atypical cells. A statistically significant correlation between the malignant and normal cells was obtained for the autophagy positivity (P = 0.012). In view of the staining intensity of MAP1LC3A protein by the H-score method, a significant correlation was found between the NILM-INF and the normal cells (P = 0.015). Conclusions: Autophagy was detected in various cervicovaginal smears for the first time in this study. Our findings indicate that an autophagy process is essential in infectious cells as well as in the transformation of atypical cells into malignant cells in carcinogenesis.

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OBJECTIVE: We aimed to investigate the factors associated with UTI in patients with T2D whether being treated with SGLT-2i or not. METHODS: Adult patients with T2D, whose urine culture results were available, were analyzed retrospectively. Urine culture was obtained from mid-flow urine. Antibacterial treatment was given to the patients with UTI, which was defined by positive urine cultures and/or clinical findings. We grouped the patients as follows: Group A, those treated with SGLT-2i; and Group B, those not treated with SGLT-2i. RESULTS: A total of 101 patients were included. Median age was 56 (45-67), 56.4% (n = 57) of the patients were female. Urine culture was positive in 54.9% (n = 28) and 16% (n = 8) of Group A (n = 51) and Group B (n = 50), respectively. Of those for whom urine culture was positive, Escherichia coli was isolated in 83.3% (n = 30), and both Escherichia coli and Klebsiella pneumoniae (K.pneumoniae) were isolated in 16.7% (n = 6). Klebsiella pneumoniae was isolated only from Group A. The need for and duration of hospitalization were higher in Group A (p < 0.001). UTI was detected in 60 patients. ROC analysis showed that a HbA1c of > 5.8% was associated with UTI with good accuracy (AUC: 0.835, p < 0.001). In multiple logistic regression analysis, SGLT-2i use and glucosuria were positive predictors for UTI (p = 0.004, Odds Ratio: 1984.013; and p = 0.028, and Odds Ratio: 12.480, respectively). CONCLUSION: Besides the association of HbA1c and BMI with UTI, SGLT-2i use and glucosuria predicted UTI. Urine culture is important with respect to the choice of antibacterial treatment, especially in those patients under SGLT-2i treatment. The effect of SGLT-2i on the development of UTI is independent of baseline BMI score or HbA1c.

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Pigeon aviadenovirus A and Pigeon circovirus are both DNA viruses, infect and cause severe clinical diseases in pigeons. These viruses are associated with an immunosuppression syndrome similar to 'Young Pigeon Disease Syndrome' (YPDS). This study reports the identification of a natural co-infection, with severe clinical signs (crop vomiting, watery diarrhoea, anorexia and sudden death) of Pigeon aviadenovirus A and Pigeon circovirus in a breeding pigeon flock in Central Anatolia, Turkey. Both viruses were isolated from pigeons pooled internal organs using primary chicken embryo kidney cell cultures (CEKC) and specific pathogen-free (SPF) embryonated chicken eggs. Also, both viruses were identified by PCR amplification followed by Sanger sequencing whereas histopathological examination showed degenerated hepatocytes with basophilic intranuclear viral inclusions. As known, both viruses typically have similar transmission characteristics and common clinical manifestations; however, co-infection may exacerbate the disease with devastating outcomes. This is the first report of its kind in Turkey for those viruses and is essential for the protection against these kinds of infections in pigeons.

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PURPOSE: Familial neurohypophyseal diabetes insipidus (FNDI), a rare disorder, which is clinically characterized by polyuria and polydipsia, results from mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The aim of this study was to perform functional analyses of three different mutations (p.G45C, 207_209delGGC, and p.G88V) defined in the AVP-NPII gene of patients diagnosed with FNDI, which are not included in the literature. METHODS: For functional analysis studies, the relevant mutations were created using PCR-based site-directed mutagenesis and restriction fragment replacement strategy and expressed in Neuro2A cells. AVP secretion into the cell culture medium was determined by radioimmunoassay (RIA) analysis. Fluorescence imaging studies were conducted to determine the differences in the intracellular trafficking of wild-type (WT) and mutant AVP-NPII precursors. Molecular dynamics (MD) simulations were performed to determine the changing of the conformational properties of domains for both WT and 207-209delGGC mutant structures and dynamics behavior of residues. RESULTS: Reduced levels of AVP in the supernatant culture medium of p.G45C and p.G88V transfected cells compared to 207_209delGGC and WT cells were found. Fluorescence imaging studies showed that a substantial portion of the mutant p.G45C and p.G88V AVP-NPII precursors appeared to be located in the endoplasmic reticulum (ER), whereas 207_209delGGC and WT AVP-NPII precursors were distributed throughout the cytoplasm. CONCLUSIONS: The mutations p.G45C and p.G88V cause a failure in the intracellular trafficking of mutant AVP-NPII precursors. However, 207_209delGGC mutation does not result in impaired cellular trafficking, probably due to not having any significant effect in processes such as the proper folding, gain of three-dimensional structure, or processing. These results will provide valuable information for understanding the influence of mutations on the function of the AVP precursor hormone and cellular trafficking. Therefore, this study will contribute to elucidate the mechanisms of the molecular pathology of AVP-NPII mutations.

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This study aims to show the changing effects of Androctonus crassicauda venom and A. crasicauda specific antivenom during pregnancy in brain tissue of dams and their pups. Totally, 12 pregnant-Wistar Albino rats were randomly divided into two groups as venom-antivenom administration (n = 6) and control groups (n = 6). In venom-antivenom administration group (VAV), the sublethal dose of A. crassicauda venom dissolved in 1 mL physiological saline solution was subcutaneously (s.c.) injected into pregnant rats during organogenesis period (between 7 and 13 days of pregnancy). Four hours after each venom injection, 1 mL/s.c. dose of the specific anti-venom was administered to rats of VAV group. The rats in control group were given sterile saline solution 1 mL/s.c. In both groups, the fetuses were surgically delivered on the 21st day of pregnancy; dams and pups were sacrificed on postnatal 21 days, and their brain tissues were removed. The brain tissue of dams and their pups were evaluated histopathologically and immunohistochemically. To show the neuronal damages, 8-hydroxy-2-deoxyguanosine (8-OHDG) and amyloid beta precursor protein (ABPP) immunoexpressions were scored in cerebrum, cerebellum, pons and medulla oblongata of brain. To show the neuroprotection, reelin and beta-arrestin immunoexpressions were scored again in the same way. In this context, 8-OHDG immunoexpressions were increased in neocortex, hippocampus and nucleus accumbens when compared with that of control group. Amyloid beta precursor protein was negative in both groups. Reelin and beta-arrestin partly increased in fore and mid brain of VAV group as a reaction against neuronal damages when compared with that of control pups. The authors believe that prompt intervention using anti-venom to scorpion envenomation can partly stop neuronal damages. This neuroprotection may be increased to high and serial doses of anti-venom to save neonatal lives.

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Polycystic kidney disease (PKD) is one of the most common hereditary diseases in cats, with high prevalence in Persian and Persian-related cats. PKD is caused mainly by an inherited autosomal dominant (AD) mutation, and animals may be asymptomatic for years. We screened 16 cats from various breeds exhibiting a renal abnormality by ultrasound examination and genotyped them for the c.10063C>A transversion on exon 29 of the polycystin-1 (PKD1) gene, by PCR-restriction fragment length polymorphism (PCR-RFLP). Among these cats, a Siamese nuclear family of 4 cats with ancestral hereditary renal failure were screened by whole-genome sequencing (WGS) to determine novel variations in genes associated with both AD and autosomal recessive PKD in humans. During the study period, one cat died as a result of renal failure and was forwarded for autopsy. Additionally, we screened 294 cats asymptomatic for renal disease (Angora, Van, Persian, Siamese, Scottish Fold, Exotic Shorthair, British Shorthair, and mixed breeds) to determine the prevalence of the mutation in cats in Turkey. Ten of the symptomatic and 2 of the asymptomatic cats carried the heterozygous C → A transversion, indicating a prevalence of 62.5% and 0.68%, respectively. In the WGS analysis of 4 cats in the Siamese nuclear family, novel variations were determined in the fibrocystin gene (PKHD1), which was not compatible with dominant inheritance of PKD.

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Objective: Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by a renal insensitivity to arginine vasopressin (AVP). In the majority of the cases, CNDI is caused by mutations in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a novel mutation in the AVPR2 gene causing CNDI in a 6-year-old boy, presenting with growth failure and dull normal cognitive functions. Methods: The proband was the third off-spring of non-consanguineous parents and had polyuria (4.3 L/day), polydipsia (5 L/day). The diagnosis of CNDI was established by a water-deprivation test and a desmopressin challenge test. Genetic studies were also carried out in the mother, siblings and affected family members, since excessive fluid intake and diuresis were also reported in these individuals. All exons of the AVPR2 gene for all participants were amplified and sequenced. Bioinformatics analysis for wild-type and mutant AVPR2 were obtained with Swiss-Model and UCSF Chimera 1.10.2. Results: A novel, hemizygous, missense mutation was identified at the position 80th in exon 2 (p.H80Y) of AVPR2 in the proband. The proband's mother, maternal aunt and grandmother were heterozygous and his maternal uncle was hemizygous for this mutation. Bioinformatic analysis indicates this mutation would cause significant conformational changes in protein structure. Conclusion: p.H80Y mutation will cause inappropriate folding of the protein compromising water homeostasis via AVPR2 and AVP and leading to diabetes insipidus. We suggest that future functional investigations of the H80Y mutation may provide a basis for understanding the pathophysiology of the NDI in patients with this variant.

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