CAG repeat expansion in the Huntington’s disease gene shapes linear and circular RNAs biogenesis

Alternative splicing (AS) appears to be altered in Huntington’s disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD). The expanded Htt CAG repeats further reflect on a previously neglected, global impairment of back-splicing, leading to decreased circular RNAs production in neural progenitors. Integrative transcriptomic analyses unveil a network of transcriptionally altered micro-RNAs and RNA-binding proteins (CELF, hnRNPS, PTBP, SRSF, UPF1, YTHD2) which might influence the AS machinery, primarily in neural cells. We suggest that this unbalanced expression of linear and circular RNAs might alter neural fitness, contributing to HD pathogenesis

Effect of Mitomycin - C and Triamcinolone on Preventing Urethral Strictures

Urethral stricture is a common disease with high recurrence rate. Several manipulations were defined to prevent the recurrence but the results were disappointing. This study aimed to evaluate the efficacy of triamcinolone and mitomycin-C on urethral stricture formation and their effect on inhibition of urethral fibrosis. A total of 24 New Zealand rabbits were divided into 3 groups. Urethras of rabbits were traumatized with pediatric resectoscope. Resection area was irrigated with 10mL saline, swapped with a cotton wool soaked with 0.5mg/mL MMC and injected by 40mg triamcinolone in groups 1, 2 and 3 respectively. Retrograde urethrogram was performed at 28th day of procedure and the urethra was removed for histopathologic evaluation. There were significant differences in urethral diameters and in lumen reduction rate between the control and study groups (p< 0.001). Compared to control group, all treatment groups showed mild fibrosis, less collagen bundle irregularity, and lower numbers of fibroblasts (p= 0.003). The Tunnel assay showed that the number of apoptotic cells in the submucosal connective tissue was quantitatively higher in control groups (p= 0.034). In the view of efficacy and safety, MMC and triamcinolone have the potential to replace the use of stents, clean intermittent catheterization, or long term catheters following internal urethrotomy. There were no statistically significant differences between two agents in terms of preventing urethral stricture formation in the present study. Mitomycin C and triamcinolone decreased the recurrence rates of urethral stricture

Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. � 2016 Michal Lotem et al

Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review

Toy M, Önder FO, Wörmann T, et al. Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: a systematic review. BMC infectious diseases. 2011;11(1): 337.BACKGROUND: To provide a clear picture of the current hepatitis B situation, the authors performed a systematic review to estimate the age- and region-specific prevalence of chronic hepatitis B (CHB) in Turkey. METHODS: A total of 339 studies with original data on the prevalence of hepatitis B surface antigen (HBsAg) in Turkey and published between 1999 and 2009 were identified through a search of electronic databases, by reviewing citations, and by writing to authors. After a critical assessment, the authors included 129 studies, divided into categories: 'age-specific'; 'region-specific'; and 'specific population group'. To account for the differences among the studies, a generalized linear mixed model was used to estimate the overall prevalence across all age groups and regions. For specific population groups, the authors calculated the weighted mean prevalence. RESULTS: The estimated overall population prevalence was 4.57, 95% confidence interval (CI): 3.58, 5.76, and the estimated total number of CHB cases was about 3.3 million. The outcomes of the age-specific groups varied from 2.84, (95% CI: 2.60, 3.10) for the 0-14-year olds to 6.36 (95% CI: 5.83, 6.90) in the 25-34-year-old group. CONCLUSION: There are large age-group and regional differences in CHB prevalence in Turkey, where CHB remains a serious health problem

The impact of biologics and tofacitinib on cardiovascular risk factors and outcomes in patients with rheumatic disease: a systematic literature review

Introduction Rheumatic diseases are autoimmune, inflammatory diseases often associated with cardiovascular (CV) disease, a major cause of mortality in these patients. In recent years, treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), either as monotherapy or in combination with other drugs, have become the standard of treatment. In this systematic literature review, we evaluated the effect of treatment with biologic or tofacitinib on the CV risk and outcomes in these patients. Methods A systematic search was performed in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for articles reporting on CV risk and events in patients with rheumatic disease treated with a biologic agent or tofacitinib. Articles identified were subjected to two levels of screening. Articles that passed the first level based on title and abstract were assessed on full-text evaluation. The quality of randomized clinical trials was assessed by Jadad scoring system and the quality of the other studies and abstracts was assessed using the Downs and Black instrument. The data extracted included study design, baseline patient characteristics, and measurements of CV risk and events. Results Of the 5722 articles identified in the initial search, screening yielded 105 unique publications from 90 unique studies (33 clinical trials, 39 prospective cohort studies, and an additional 18 retrospective studies) that reported CV risk outcomes. A risk of bias analysis for each type of report indicated that they were of good or excellent quality. Importantly, despite some limitations in data reported, there were no indications of significant increase in adverse CV events or risk in response to treatment with the agents evaluated. Conclusions Treatment with biologic or tofacitinib appears to be well-tolerated with respect to CV outcomes in these patients

The expression and relationship of adipo R1/R2 in gastric intestinal metaplasia

Background: Adiponectin (ApN) is a 244-amino acid protein mainly secreted from the adipose tissue and involved in various physiological functions. ApN exerts its metabolic effects by binding to two major receptors: adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Recent studies have reported ApN's involvement in the progression of cancer. However, there are no studies evaluating the relationship between Adipo-R1/R2 expression and gastric intestinal metaplasia (IM), which is a predisposing factor in gastric cancer (GC) development, and Helicobacter pylori H. pylori infection. Aims: In this study we aimed to investigate the relationship between the Adipo-R1/-R2 expression and H. pylori infection in patients with GC and gastric IM. Materials and Methods: Forty patients that underwent gastric resection and 56 patients that developed gastric IM were included in the study. The Adipo-R1/-R2 expression and the presence of H. pylori were examined immunohistochemically. The univariate analyses showed that the expression of Adipo-R1/-R2 in GC patients was significantly lower compared to both complete metaplasia (CM) and incomplete metaplasia (ICM) patients (p <0.0001 for both). Results: According to multiple multinomial logistic regression analysis, Adipo-R1/-R2 expression in the CM group was significantly higher than in the GC group (p = 0.05, p = 0.014, respectively). Moreover, Adipo-R1/-R2 expression was significantly higher in ICM group compared to the GC group (p=0.012, p=0.045, respectively). However, in both analyses no significant difference was determined in terms of H. pylori positivity between the groups.Conclusion: The resulting data suggests that ApN plays a role in GC processes via Adipo-R1/-R2 receptors

Source and reservoir rock potential of tertiary units in the Kozakli Basin, Central Anatolia, Turkey

The authors present the hydrocarbon source rock potential and reservoir properties of the Eocene Formations in the Central Anatolian Kozakli Basin. Potential source and reservoir rocks in the Kozakli basin include transgressive-regressive bank carbonates, fore-bank, deep-marine shales and sandstones, and coal and bituminous facies. The organic geochemical data of the Middle Eocene shales (Sarilar Formation) show that inadequate to marginal source rock qualities, and marginally mature to overmature characteristics, resulting from heat flow regime of the studied area. Alemli Member of the ¯ncik Formation is good to excellent according to TOC wt% and immature to mature source rock from Tmaxvalues. Sedimentological features and age data indicate that the Uzunlu Formation was deposited under the control of antecedent topography. Reservoir properties of the Uzunlu Formation and Keklicek member indicate that the carbonate unit is not adequate for reservoir rock. However, siliciclastics of the Sarilar Formation could be reservoir potential due to its high porosity and permeability values. © 2015 Taylor and Francis Group, LLC.12B4343017This study is funded by a grant from by Scientific Research Project Directory of Ankara University under project number 12B4343017

Evaluation of the effectiveness of training with nebulizer type toy in three-six year old children receiving nebulizer therapy [Nebülizatör tedavisi alan üç-altı yaş grubu çocuklarda oyuncak tipi nebülizatör ile verilen eğitimin etkinliğinin değerlendirilmesi]

Objective: The application training given to the mothers of 3-6 year old group nebulizer by toys type nebulizer determines the maternal application skill behavior, level of anxiety and the effect of the child on anxiety. Material and Methods: The randomized controlled study was carried out in the children’s services of Okmeydanı Training and Research Hospital in İstanbul between February 2017-January 2018. The sample of the study consisted of 60 children and their mothers aged 3-6 who took nebulizer treatment. In the collection of research data, descriptive information form, Children’s Emotional Manifestation Scale, State and Trait Anxiety Scale, steps to evaluate the patient’s ability to use devices, nebulizer training brochure, toy type nebulizer was used. Results: The mean anxiety scores of children in the experimental group were decreased during inhaler treatment, and the anxiety scores of children in the control group were increased during the operation. There was no statistically significant difference between the mean scores of the control and experiment group pre-training application and evaluation stages, the second and the third evaluation. There was no statistically significant difference between pre- and post-treatment anxiety scores of mothers in the working and control group. Conclusion: Educational training with toy type nebulizer was found to have positive effects on children’s anxiety during nebu-lization treatment, it was determined that there was an increase in the mothers’ post-training skills and no effect on their anxiety. Copyright © 2019 by Türkiye Klinikleri

Modern halolites (halite oolites) in the Tuz Golu, Turkey

Halite oolites (halolites) and pisoids (halopisoids) precipitate yearly (in summer) in the brine conduits of the saltpans in the Tuz Golu saline lake (Central Anatolia, Turkey). These hatolites are well rounded and spherical, ranging between 0.7 and 2 cm in size. They are composed of coarse-grained halite crystals as the nucleus, and by concentric halite laminae with a radial fabric as the cortex. The cortex is subdivided into inner, middle, and outer zones, each zone showing different mineralogical and morphological features. These features include the presence of. organic matter particles, native sulphur globules, gypsum-anhydrite-calcite laminae, quartz-chlorite-celestite-then-nonatrite laminae, submicroscopic halite crystals, and microborings, cavities and corrosion-like structures