Male- and female-specific microRNA expression patterns in a mouse model of methanol poisoning.

The aims of this study were to determine the miRNAs involved in the methanol poisoning, and identify the male- and female-specific miRNA expression patterns in mice. Methanol was applied orally at the doses of 4 g/kg and 8 g/kg to induce mild and severe methanol poisoning in Balb/c mice. miRNA expression levels were detected at 3 different time periods (30, 60, and 180 min) following methanol exposure. miRNA expression profiles were determined using the high-throughput Fluidigm BioMark real-time PCR. We observed that serum miR-206 expression in male mice and miR-6357 expression in female mice could be an indicator of methanol poisoning. miR-9-3p downregulation and miR-1187 upregulation could be important for liver tissue. miR-3106-5p and miR-133a-5p upregulations and miR-122-3p downregulation could be poison biomarkers for ocular tissue in male mice. However, miR-194-5p downregulation could be a biomarker for ocular tissue in female mice. miR-122-5p and miR-124-3p downregulations and miR-499a-5p upregulation appeared to be important for kidney tissue in male mice. miR-543 and miR-6342 upregulations could be potential candidate biomarkers for kidney tissue in female mice. Our study is the first to report that differential miRNA expressions are involved in blood and tissues in male and female mice after methanol treatment.

Predicting Progression of Autosomal Dominant Polycystic Kidney Disease by Changes in the Telomeric Epigenome.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of chronic kidney disease with Polycystin (PKD) 1 and 2 gene mutation. However, the intra-familial variability in symptoms further suggests a non-Mendelian contribution to the disease. Our goal was to find a marker to track the epigenetic changes common to rapidly progressing forms of the disease. The risk of ADPKD increases with age, and aging shortens the telomere length (TL). Telomeres are a nucleoprotein structure composed mainly of three complexes, shelterin, CST and RNA-containing telomere repeat(TERRA), which protects the ends of chromosomes from degradation and fusion, and plays a role in maintaining cellular stability and in the repair of telomeric damage. TERRAs are transcribed from telomeric regions and a part of them is engaged in a DNA/RNA hybrid (R-loop) at each chromosome end. We tracked TL and TERRA levels in blood samples of 78 patients and 20 healthy control. Our study demonstrates that TL was shortened and TERRA expression levels in the DNA-attached fraction increased in autosomal dominant polycystic kidney patients with mutations in PKD1 and PKD2 compared to the control group. Moreover, it was observed that the expression of TERRA engaged in the R-loop was higher and the length of telomeres shorter in patients with ADPKD who showed rapid disease progression. Intrafamilial variation in TL and TERRA levels with the same mutation would indicate reliable epigenetic potential biomarkers in disease monitoring.

Mouse Paternal RNAs Initiate a Pattern of Metabolic Disorders in a Line-Dependent Manner.

A wide range of diseases result from environmental effects, and the levels of many native transcripts are altered. The alteration of non-coding RNAs (ncRNAs) and transmission of the variation to the next generation is increasingly recognized as a marker of disease. However, the determining signals and mechanisms of RNA-induced heritability remain unclear. We performed functional tests with four different genotypes of mice maintained on a high-fat diet to trace the transfer of the obesity/diabetes phenotype to the next generation in order to detect common signals. Two founders of four mouse lines (B6/D2 hybrid and Dnmt2 -/-C57BL/6 ) resist and do not change their phenotype while their sperm RNAs after microinjection into fertilized mouse eggs transfer the newly acquired phenotypes in a susceptible inbred line (C57BL/6 or Balb/c). Unexpectedly, in the same line of experiments, sperm RNA from animals raised on a normal diet when mixed with the sperm RNA from animals raised on a diet high in fat or synthetic miR-19b (inducer of obesity) affects or prevents the development of obesity and diabetes. However, it remains unclear what happens to ncRNA signaling under diet. With a comprehensive new analysis of the transcripts maintained as an RNA/DNA hybrid in sperm, we suggest that a fraction of the RNAs are stably attached to the genome. Thus, we propose that changes in the dynamics of ncRNA retention on DNA by factors such as transcriptional variations or lack of adequate methylation could serve as molecular markers to trace these epigenetics events.

The Characterization of Sex Differences in Hypoglycemia-Induced Activation of HPA Axis on the Transcriptomic Level.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis using an insulin tolerance test (ITT) is a medical diagnostic procedure that is frequently used in humans to assess the HPA and growth-hormone (GH) axes. Whether sex differences exist in the response to ITT stress is unknown. Thus, investigations into the analysis of transcripts during activation of the HPA axis in response to hypoglycemia have revealed the underlying influences of sex in signaling pathways that stimulate the HPA axis. We assessed four time points of ITT application in Balb/c mice. After insulin injection, expression levels of 192 microRNAs and 41 mRNAs associated with the HPA, GH and hypothalamic-pituitary-gonadal (HPG) axes were determined by real-time RT-PCR in the hypothalamus, pituitary and adrenal tissues, as well as blood samples (Raw data accession: https://drive.google.com/drive/folders/10qI00NAtjxOepcNKxSJnQbJeBFa6zgHK?usp=sharing ). Although the ITT is commonly used as a gold standard for evaluating the HPA axis, we found completely different responses between males and females with respect to activation of the HPA axis. While activation of several transcripts in the hypothalamus and pituitary was observed after performing the ITT in males within 10 min, females responded via the pituitary and adrenal immediately and durably over 40 min. Additionally, we found that microRNA alterations precede mRNA responses in the HPA axis. Furthermore, robust changes in the levels of several transcripts including Avpr1b and Avpr2 observed at all time points strongly suggest that transcriptional control of these genes occurs mostly via differential signaling in pituitary and blood between males and females. Male and female HPA axis responses to ITT involve a number of sophisticated regulatory signaling pathways of miRNAs and mRNAs. Our results highlight the first robust markers in several layers of HPA, HPG and GH axis involved in ITT/hypoglycemia stress-induced dynamics.

Comparison of Transoral/Transnasal Endoscopic-Guided Adenoidectomy with Endoscopic Nasopharyngeal Inspection at the End of Curettage Adenoidectomy.

The purpose of this study was to evaluate the efficacy of transoral or transnasal endoscopic-guided adenoidectomy compared with endoscopic nasopharyngeal inspection at the end of curettage adenoidectomy. A prospective case series of patients who had adenoidectomy. A total of 27 girls and 34 boys (age range 2.5-18 years) in whom adenoidectomy with or without tonsillectomy procedure was planned were included in the study. The cases were divided into three groups. Group 1 Transoral endoscopic-guided adenoidectomy performed patients. Group 2 Transnasal endoscopic-guided adenoidectomy performed patients. Group 3 Transnasal endoscopic nasopharyngeal exploration performed at the end of the conventional curettage adenoidectomy. The study was completed on 61 children. Mean age and sex frequency were not significant different between the groups. Mean operative time were 11.6 ± 2.9, 15.6 ± 4.4 and 9.7 ± 2 min, respectively (p > 0.05). On the other hand, significant differences were observed in operative time between group 1 and group 2 (p < 0.05), and between group 2 and group 3 (p < 0.05). Transnasal endoscopic examination at the end of curettage adenoidectomy is an appropriate method to assess the residual adenoid tissue after conventional curettage adenoidectomy. Also, operative time of this method is shorter than transoral or transnasal endoscopic-guided adenoidectomy. We recommend transnasal endoscopic inspection in all patients after conventional curettage adenoidectomy.

[Nasal foreign bodies: an analysis of 130 patients]. / Burunda yabanci cisim: 130 hastanin degerlendirilmesi.

OBJECTIVES: This study aims to investigate clinical manifestations and treatment protocols in patients with a diagnosis of nasal foreign bodies. PATIENTS AND METHODS: We retrospectively evaluated 130 patients (72 males, 58 females; mean age 3.65±2.31 years; range 15 month to 72 years) who were diagnosed with nasal foreign bodies and received treatment between November 2008 and July 2013. Age and sex of the patients, type of foreign body, side of presentation, signs and symptoms, management practices, and outcomes were recorded. RESULTS: Most of the patients were children between the ages of 2 and 5 (n=113, 86.9%). The most common foreign bodies were small plastic toys (43.8%), nut, walnut, corn, bean and the other seed grains (29.2%). Foreign bodies were detected in the right nasal passage in 74 patients (56.9%), left nasal passage in 54 patients (41.6%) and both nostrils in two patients (1.5%). Of the patients, 92.3% were admitted to our clinic within 24 hours. CONCLUSION: Nasal foreign bodies are frequent encountered in the emergency setting of ear, nose, and throat diseases. Although they are not life-threatening conditions, they require urgent intervention, as they may lead to several complications in the long-term. Parents and caregivers of children should keep objects which can be put into the nose away and be instructed that they should consult a physician in case of nasal foreign bodies.

Evaluation of middle ear pressure in the early period after adenoidectomy in children with adenoid hypertrophy without otitis media with effusion.

OBJECTIVE: Our aim was to analyze the changes in middle ear pressure in the early period after adenoidectomy in children with adenoid hypertrophy without otitis media with effusion. METHODS: This prospective, descriptive study was performed on 64 patients (with normal tympanic membranes and tympanograms) undergoing adenoidectomy or adenotonsillectomy. All patients were operated by single experienced team using curettage technique. First tympanometry was done on the day before surgery. Tympanometry was repeated on the first-, third-, and seventh-day after the operation. Patients are separated into two groups according to age as patients younger than 6 years (Group A) and patients older than 6 years (Group B). All data were separately evaluated for each ear using Jerger Classification. RESULTS: Of the 64 patients included in the study, 35 were male and 29 were female, and the average age was 91.01 ± 37.4 (35-178) months. Pathological decreases in the middle ear pressures of at least one ear were determined in 48 (75%) patients on the first postoperative day and in 10 (15.6%) patients on the third postoperative day. Middle ear pressures returned to preoperative values by the seventh postoperative day except in two patients. There were statistically significant differences (p<0.0001) among preoperative and first, third, and seventh postoperative day mean middle ear pressure. There were no statistically significant differences between Groups A and B in terms of tympanometry values of both ears obtained preoperatively and on the first, third, and seventh postoperative day. CONCLUSION: In our study, temporary eustachian dysfunction and aural fullness occur in the early period after adenoidectomy and/or adenotonsillectomy. This situation may be due to post-surgery clots and edema in nasopharynx. We consider that tubal orifice can be exposed to surgical trauma as adenoidectomy surgeries are done by curettage technique. There is a need for comparative studies using microdebrider or laser adenoidectomy accompanied by an endoscope.