Evaluation of Plasma miR-17-5p, miR-24-3p and miRNA-223-3p Profile of Hepatitis C Virus-Infected Patients after Treatment with Direct-Acting Antivirals.

The expression of miR-223-3p, miR-17-5p, and miR-24-3p was evaluated in hepatitis C virus (HCV) patient serum samples, collected before DAA treatment and after a sustained virological response (SVR). Fifty HCV patients were stratified based on their liver damage stages into three different subgroups (21 with chronic hepatitis-CH, 15 with cirrhosis, and 14 with hepatocellular carcinoma-HCC). Considering the entire HCV population, the miRNA expression levels were significantly downregulated after the SVR compared to pre-treatment ones (p < 0.05). Stratifying the patients based on liver damage, the post-SVR values of the three miRNAs were significantly downregulated compared to the pre-treatment levels for both cirrhosis and HCC patients. No significant differences emerged from the analysis of the CH group. To our knowledge, this is the first study to detail the behavior of miR-223-3p, miR-17-5p, and miR-24-3p levels in patients with HCV-related CH, cirrhosis, and HCC after DAA therapy. Our findings show that HCV-infected patients have different miRNA profiles before and after treatment with DAAs, strongly suggesting that miRNAs may be involved in the pathogenesis of HCV-related damage. In this respect, the correlation observed among the three studied miRNAs could imply that they share common pathways by which they contribute the progression of HCV-induced chronic liver damage.

Maternal separation increased memory function and anxiety without effects of environmental enrichment in male rats.

Maternal separation is a detrimental postnatal influence, whereas environmental enrichment is a therapeutic and protective agent. It is unclear if long-term environmental enrichment can compensate for the effects of maternal separation stress on memory-related alterations. This study examined how environmental enrichment affected memory functions, anxiety level, Grin2a, Grin2b, BDNF, and cFos expressions in the maternally separated rats. There are seven groups in this study: control (C), maternal separation+standard cage (MS), maternal separation + enriched cage (MSE), enriched cage (E), the maternal separation that decapitated at postnatal 21 (MS21) and standard cage that decapitated at PN21 (C21) for hormone and gene expression analysis. The maternal separation procedure consisted of postnatal 21 days. Learning and memory performance were determined with the Morris water tank test; anxiety and locomotor activity were examined with the open field and elevated plus-maze test. The expression levels of genes were measured by the RT-PCR method. Blood corticosterone level was evaluated by the ELISA method. Results showed that MS increased memory performance, locomotor activity, and anxiety, but it did not change gene expression levels. An enriched environment did not change the memory performance, locomotor activity, and related gene expression levels. MSE group increased their memory performance, but the anxiety, locomotor activity, and gene expression level did not change. Grin2a, Grin2b, and BDNF gene expression and corticosterone levels increased in the MS21 group. Maternal separation increased memory performance, but it also increased anxiety. Environmental enrichment alone was insufficient to cause alterations in the memory performance.

Retrospective analysis of patients diagnosed with severe hyponatraemia in the emergency department.

Background . We investigated the demographic, aetiological and clinical characteristics of patients who presented to the emergency department and had severe hyponatraemia. Methods . We retrospectively evaluated 1171 patients who presented to the emergency department and were diagnosed with severe hyponatraemia. Results . Over half the patients studied were women (53.5%). The mean age of women was higher (p<0.0001). The most common complaint was dyspnoea (16.8%) and 42.5% of the patients had an oral intake disorder. In addition, 22.3% of the patients were on loop diuretics. About 76.3% of patients were conscious, and the mean sodium level of these patients was higher than the mean sodium level of those who responded to verbal and painful stimuli (p<0.001). Severe isolated hyponatraemia was observed in 61.8% of the patients. The mortality rate was 12.8%. There was no difference between the mean sodium levels of the deceased and discharged patients (p=1.0). The mortality rate was higher in patients who had a history of cirrhosis and cancer, but was lower in patients with a history of coronary artery disease (p=0.0002, p<0.0001 and p=0.04, respectively). Conclusion . Severe hyponatraemia was more prevalent in women, serum sodium levels were higher in conscious patients, and the mortality rate was higher in patients who had a history of cirrhosis and cancer. We found that the mean serum sodium levels did not help in distinguishing between the deceased and discharged patients.

hsa-miR-17-5p: A Possible Predictor of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir ± Ribavirin Therapy Efficacy in Hepatitis C Infection.

Although persistent sustained viral response rates are increased in hepatitis C infection following administration of direct-acting antiviral (DAA) agents, the pre-use predictive parameters of these antivirals and the clinical progression in patients post-treatment remain unknown. To obtain data pertaining to the predictive parameters prior to the use of ombitavir/paritaprevir/ritonavir + dasabuvir and the clinical progression in patients following antiviral treatment. The expression profiles of miR-223-3p, miR-17-5p, miR-24-3p, and TLR2 - 196 to - 174 del/ins polymorphisms from the blood/serum of 34 hepatitis C virus (HCV)-infected patients pre- and post-ombitavir/paritaprevir/ritonavir + dasabuvir treatment were determined by RT-qPCR. The expression levels of miR-17-5p (P < 0.001) and miR-24-3p (P = 0.011) were significantly downregulated post-treatment as compared with those pre-treatment; however, there was no significant difference between these two groups in terms of miR-223-3p expression. In addition, there was no significant difference in TLR2 genotype or allele distribution between pre-and post-treatment (P > 0.05); nevertheless, the TLR2 del allele was decreased post-treatment (16.2%) as compared with that pre-treatment (19.1%), although the difference was not statistically significant. Moreover, a significant difference was found between the mRNA levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and HCV RNA pre-and post-treatment (P < 0.05). Further, miR-17-5p expression correlated with both ALT and AST mRNA levels post-treatment (P.

Endoscopic endonasal dacryocystorhinostomy learning curve / Curva de aprendizagem de dacriocistorrinostomia endonasal endoscópica

ABSTRACT Purpose: To compare the learning curves of the specialists in two different fields without previous endoscopic endonasal dacryocystorhinostomy experience as well as to reveal the related complications with surgical success rates. Methods: We retrospectively investigated 90 patients who received consecutive endoscopic endonasal dacryocystorhinostomy with mucosa preservation by an ophthalmologist (Group 1, n=45) and an otorhinolaryngologist (Group 2, n=45) between October 2017 and October 2019. Patients who were admitted with epiphora complaints and diagnosed with primary acquired nasolacrimal duct obstruction through lacrimal irrigation test and aged >18 years with at least 6 months of follow-up were included in the study. In all cases, additional pathologies such as septum deviation were evaluated by performing maxillofacial imaging. Patients' medical records were evaluated in terms of surgery duration, complications, and functional achievements. Results: The mean surgical duration of the patients in Group-2 was 36.27 ± 11.61 min, while it was 43.62 ± 16.89 min in Group-1; the difference was statistically significant (p=0.018). Functional achievements in Group 1 was 84.4% (73.3% in the first set of 15 cases, 93.3% in the last set of 15 cases) in Group 2; this rate was 88.9% (80% in the first set of 15 cases, 93.3% in the last set of 15 cases), and the difference was not statistically significant (p=0.53). Septum intervention in addition to endoscopic surgery in both the groups (p=0.03, p=0.005, respectively) and intense bleeding during surgery (for both the groups, p<0.0001) significantly decreased the functional success. Conclusion: Endoscopic endonasal dacryocystorhinostomy, performed after the necessary training, can provide high success and low complication rates when even conducted by ophthalmologists who are unfamiliar with endoscopic surgery after an experience of 30 cases.

RESUMO Objetivos: O objetivo deste estudo é comparar as curvas de aprendizagem dos especialistas em dois campos diferentes sem experiência prévia de dacriocistorrinostomia endonasal endoscópica e revelar as complicações com as taxas de sucesso cirúrgico. Métodos: Foram investigados retrospectivamente 90 pacientes que receberam dacriocistorrinostomia endonasal endoscópica consecutiva com preservação da mucosa realizada por um oftalmologista (Grupo 1, n=45) e realizada por um otorrinolaringologista (Grupo 2, n=45) entre outubro de 2017 e outubro de 2019. Foram incluídos no estudo pacientes admitidos com epífora e diagnosticados com obstrução primária do ducto nasolacrimal adquirido como resultado do teste de irrigação lacrimal, com idade superior a 18 anos e com, pelo menos, 6 meses de acompanhamento. Em todos os casos, patologias adicionais, como o desvio do septo, foram avaliadas por meio da realização de imagens maxilofaciais. Os prontuários dos pacientes foram avaliados quanto à duração da cirurgia, complicações e desempenho funcional. Resultados: A média de duração cirúrgica dos pacientes no Grupo-2 foi de 36,27 ± 11,61 minutos, enquanto no Grupo-1 foi de 43,62 ± 16,89 minutos, sendo a diferença estatisticamente significativa (p=0,018). O desempenho funcional no Grupo 1 foi de 84,4% (73,3% nos primeiros 15 casos, 93,3% nos últimos 15 casos) no Grupo 2, essa taxa foi de 88,9% (80% nos primeiros 15 casos, 93,3% nos últimos 15 casos) e a diferença não foi estatisticamente significativa (p=0,53). A intervenção do septo além da cirurgia endoscópica em ambos os grupos (p=0,03, p=0,005, respectivamente) e sangramento intenso durante a cirurgia (para ambos os grupos, p<0,0001) diminuiu significativamente o sucesso funcional. Conclusão: A dacriocistorrinostomia endonasal endoscópica, realizada após o treinamento necessário, pode ser realizada com alto sucesso e com baixas taxas de complicações por oftalmologistas que não estão familiarizados com a cirurgia endoscópica após adquirirem experiência com trinta casos.

Endoscopic endonasal dacryocystorhinostomy learning curve.

PURPOSE: To compare the learning curves of the specialists in two different fields without previous endoscopic endonasal dacryocystorhinostomy experience as well as to reveal the related complications with surgical success rates. METHODS: We retrospectively investigated 90 patients who received consecutive endoscopic endonasal dacryocystorhinostomy with mucosa preservation by an ophthalmologist (Group 1, n=45) and an otorhinolaryngologist (Group 2, n=45) between October 2017 and October 2019. Patients who were admitted with epiphora complaints and diagnosed with primary acquired nasolacrimal duct obstruction through lacrimal irrigation test and aged >18 years with at least 6 months of follow-up were included in the study. In all cases, additional pathologies such as septum deviation were evaluated by performing maxillofacial imaging. Patients' medical records were evaluated in terms of surgery duration, complications, and functional achievements. RESULTS: The mean surgical duration of the patients in Group-2 was 36.27 ± 11.61 min, while it was 43.62 ± 16.89 min in Group-1; the difference was statistically significant (p=0.018). Functional achievements in Group 1 was 84.4% (73.3% in the first set of 15 cases, 93.3% in the last set of 15 cases) in Group 2; this rate was 88.9% (80% in the first set of 15 cases, 93.3% in the last set of 15 cases), and the difference was not statistically significant (p=0.53). Septum intervention in addition to endoscopic surgery in both the groups (p=0.03, p=0.005, respectively) and intense bleeding during surgery (for both the groups, p<0.0001) significantly decreased the functional success. CONCLUSION: Endoscopic endonasal dacryocystorhinostomy, performed after the necessary training, can provide high success and low complication rates when even conducted by ophthalmologists who are unfamiliar with endoscopic surgery after an experience of 30 cases.

Possible relationship between IL28B rs12979860 and TLR2 -196 to -174 del/ins polymorphisms and the liver fibrosis stage in hepatitis C patients.

It has been shown that host factors play an important role in the progression of hepatitis C virus (HCV) infection. Toll-like receptor 2 (TLR2) del and interleukin 28B (IL28B) T alleles can mediate liver inflammation and pathogenesis of hepatocellular carcinoma. In the present study, the possible relationship between the IL28B rs12979860 C/T and TLR2 -196 to -174 del/ins gene variants and different fibrosis stages and host factors in hepatitis C patients was investigated. IL28B and TLR2 polymorphisms in the blood of 50 hepatitis C patients at different stages of fibrosis (24 mild/moderate, 26 advanced) and 24 healthy controls were examined by RT-qPCR. The highest frequency of the TLR2 del (26.9%) and IL28B T (46.2%) alleles was found in hepatitis C patients with the most advanced fibrosis, and the lowest frequency was found in healthy controls. There was a statistically significant difference between hepatitis C patients with advanced fibrosis and healthy controls in terms of the TLR2 del (p = 0.0062) and IL28B T (p = 0.0017) allele frequencies. However, no statistically significant difference was found between the mild/moderate fibrosis and severe fibrosis patient groups in terms of genotype or IL28B and TLR2 polymorphisms (p > 0.05). In addition, there was a significant difference between patients with mild/moderate or advanced fibrosis who carried the TLR2 del allele together with the IL28B CT genotype and healthy controls. The present study emphasizes that the TLR2 and IL28B gene variants cannot be single biomarkers for the determination of fibrosis stage in hepatitis C infection but together can play an important role in predicting severe disease.

Association between acute kidney injury and mortality after successful cardiopulmonary resuscitation: a retrospective observational study.

BACKGROUND AND OBJECTIVES: Acute Kidney Injury (AKI) affect mortality and morbidity in critically ill patients. There have been few studies examining the prevalence of AKI and mortality after successful cardiopulmonary resuscitation. In the present study, we investigated the association between AKI and mortality in post-cardiac arrest patients admitted to the Intensive Care Unit (ICU). METHODS: Our retrospective analysis included 109 patients, admitted to the ICU following successful cardiopulmonary resuscitation between 2014 and 2016. We compared two scoring systems to estimate mortality. RESULTS AND DISCUSSION: AKI were diagnosed in 46.7% (n = 51) of the patients based on the RIFLE criteria and 66.1% (n = 72) using the KDIGO. Mortality rate was significantly higher among patients with AKI diagnosed according to the RIFLE criteria (p = 0.012) and those with AKI diagnosed using KDIGO criteria (p = 0.003). Receiver Operating Characteristic (ROC) analysis showed that both scoring systems were able to successfully detect mortality (Area under the ROC curve = 0.693 for RIFLE and 0.731 for KDIGO). CONCLUSION: AKI increases mortality and morbidity rates after cardiac arrest. Although more renal injury and mortality were detected with KDIGO, the sensitivity and specificity of both scoring systems were similar in predicting mortality in patients with Return of Spontaneous Circulation (ROSC).

The Usefulness of Platelet Distribution Width and Platelet Distribution Width to Lymphocyte Ratio in Predicting Severity and Outcomes in Patients with Snakebite.

INTRODUCTION: Tissue damage, inflammatory response, and hematologic abnormalities may occur in snakebite envenomation. This study aimed to evaluate the predictive ability of platelet distribution width (PDW) and platelet distribution width to lymphocyte ratio (PDWLR) in the severity and outcome of envenomation in patients with snakebites in the emergency department (ED). METHODS: All adult patients admitted to the ED after a snakebite were retrospectively evaluated. Patients were classified according to the severity of envenomation. The relationship between the PDW and PDWLR and envenomation severity and patient outcomes was analyzed. Multivariate logistic regression analysis was performed to determine the predictors of severe envenomation. Results were presented as 95% CIs with odds ratios. Statistical significance was accepted at P<0.05. RESULTS: Envenomation was classified as none/minimal in 42 patients and moderate/severe in 29. PDW and PDWLR were significantly higher in the moderate/severe group (P=0.016 and P<0.001, respectively). Cut-off values of 16.5 for PDW and 6.15 for PDWLR were related to more severe envenomation (area under the curve 0.67, 95% CI 0.55-0.78 and area under the curve 0.85, 95% CI: 0.74-0.92, respectively). Blood product replacement, thrombocytopenia, hematologic abnormality, advanced local findings, compartment syndrome/fasciotomy, antivenom dosing, and moderate/severe envenomation were associated with PDWLR >6.15 (P<0.05). In multivariate analysis, PDWLR (odds ratio 1.19 [95% CI 1-1.4]; P=0.04) was an independent predictor of severe envenomation. CONCLUSIONS: Higher PDW and PDWLR were associated with severe envenomation in patients with snakebites in the ED. PDWLR may be used as a predictor of severe envenomation and adverse outcomes.

Circulating vascular adhesion protein-1(VAP-1): a possible biomarker for liver fibrosis associated with chronic hepatitis B and C.

Vascular adhesion protein-1 (VAP-1) is a multifunctional protein that plays a role in chronic liver diseases and fibrogenesis. The present study aimed to investigate the possible association of VAP-1 levels with the severity of disease progression in chronic hepatitis (CH) B and C patients with differing stages of fibrosis (F0-4), CHB/CHC-related cirrhosis, and hepatocellular carcinoma (HCC). The VAP-1 concentration in patient sera was determined by ELISA. The VAP-1 levels were compared between the F0 group and the F1, F2, F3, F4, cirrhosis, and HCC groups of CHB patients and between the F1 group and the F2, F3, F4, cirrhosis, and HCC groups of CHC patients. The levels of VAP-1 were significantly increased in CHB patients with progressive stages of fibrosis, with the highest concentration being found in those with stage F4 (severe fibrosis). A statistically significant difference was found between F0 and F4 in patients with CHB, but no statistically significant difference was observed between F1 and F4 in patients with CHC. Interestingly, there was no statistically significant difference in VAP-1 levels between patients with cirrhosis and HCC (either CHB or CHC, independently). Moreover, no relationship was found between VAP-1 and ALT levels in either CHC or CHB patients. In general, the VAP-1 levels were significantly higher in CHB than in CHC patients (P < 0.01). In conclusion, we suggest that the VAP-1 level may be a noninvasive biomarker for monitoring the severity of fibrogenesis in patients with hepatitis B infection.

The role of COL6A1and PD-1 expressions in renal cell carcinoma.

OBJECTIVE: The COL6A1 is a gene encoding the alpha 1 polypeptide subunit of collagen 6 (COL6A1), an extracellular matrix protein subunit. Programmed cell death receptor-1 (PD-1) and its ligand, programmed cell death receptor ligand-1 (PD-L1) have been shown to have a prognostic significance in clear cell renal cell carcinomas (RCCs). In this study, we evaluated the expressions of COL6A1 and PD-1 in four different RCC subtypes. MATERIALS AND METHODS: A total of 161 radical nephrectomy and nephron-sparing surgery cases with RCCs from five different health care centers were included in this study. Clinical data of the cases were taken from electronic records of the institutions. The pathological data were collected by an expert uropathologist and re-evaluated with slides obtained from paraffin blocks of the cases. The correlation of COL6A1 and PD-1 expression with sex, age, tumor type, lymphovascular invasion (LVI), World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade, and tumor stage (pT) was analyzed with the Pearson chi-squared test. RESULTS: Patients with sarcomatoid RCC and clear cell RCC had significantly higher COL6A1 scores and intensities than in other types of RCC (p=0.004 and p=0.002, respectively). WHO/ISUP grade and, COL6A1 and PD-1 staining scores also showed positive correlation (r=0.230, p=0.004 and r=0.277, p=0.001, respectively for COL6A1 and r=0.191, p=0.018 and r=0.166, p=0.041, respectively for PD-1). The staining scores and intensities of COL6A1 and PD-1 were not different between the patients with positive and negative LVI (p>0.05). CONCLUSION: In high-grade RCCs, we found the relationship between immunohistochemical staining scores of COL6A1 and PD-1 proteins and clinical, demographic, and histopathological parameters. Our results proved that COL6A1 and PD-1 are really promising proteins as prognostic parameters and for targeted immunotherapy.

No Association between Polymorphisms of Vitamin D and Oxytocin Receptor Genes and Autistic Spectrum Disorder in a Sample of Turkish Children.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature. METHODS: Eighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Baskent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method. RESULTS: No significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found. CONCLUSION: Knowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey.

Primary headaches in pediatric patients with chronic rheumatic disease.

OBJECTIVES: To assess the presence, prevalence and clinical characteristics of primary headaches in pediatric patients with chronic rheumatic diseases such as juvenile idiopathic arthritis (JIA) and familial Mediterranean fever (FMF), and to analyze the common pathophysiological mechanisms. STUDY DESIGN: In this noncontrolled, cross-sectional study, a semi-structured 53 item headache questionnaire was administered to subjects with FMF and JIA, and interviewed a total sample size of 601 patients younger than16years of age. The questionnaires were then analyzed according to the International Headache Society's diagnostic criteria. RESULTS: Children with FMF (n=378) and JIA (n=223) were studied. Each group was then divided into two subgroups according to whether the subjects reported headache or not. 29.5% of subjects with FMF reported having migraine, 37.6% probable migraine and 32.9% tension type headache (TTH). In JIA group 28.2% were diagnosed with migraine; 41.2% with probable migraine and 30.6% with TTH. No significant difference was found between all subjects with (n=258) and without (n=343) headache for variables such as living in a crowded family (p=0.95), being the first child in the family (p=0.63), academic achievement of the child (p=0.63), high education level (higher than high school) of the mother (p=0.52) and father (p=0.46). The presence of systemic disease was reported not to be effecting the daily life at the time of evaluation by 90.2% of the children with headache and 91.0% of the children without headache (p=0.94). 81.4% of the children reported their headaches were not aggravating with the exacerbation periods of their systemic disease. Family history of hypertension was reported higher by the subjects with headache (13.5% with headache and 4.0% without headache p=0.001). Diabetes mellitus was also reported higher (5.8% with headache; 0.5% without headache; p=0.006). Family history of headache was reported in 28.2% of the patients with headache whereas it was 17.4% of the patients without headache (p<0.001). Family history of headache was reported in 28.2% of the FMF subjects with headache whereas it was 17.4% of the patients without headache (p<0.001). For JIA patients a positive family history for headache was obtained in 25.9% of children with headache notably in migraineurs (81.8%). CONCLUSION: Patients with JIA and FMF should be asked specifically about accompanying primary headaches particularly migraine headaches as they may be additional disabilities for these patients.

Affected States soft independent modeling by class analogy from the relation between independent variables, number of independent variables and sample size.

OBJECTIVE: The aim of study is to introduce method of Soft Independent Modeling of Class Analogy (SIMCA), and to express whether the method is affected from the number of independent variables, the relationship between variables and sample size. STUDY DESIGN: Simulation study. MATERIAL AND METHODS: SIMCA model is performed in two stages. In order to determine whether the method is influenced by the number of independent variables, the relationship between variables and sample size, simulations were done. Conditions in which sample sizes in both groups are equal, and where there are 30, 100 and 1000 samples; where the number of variables is 2, 3, 5, 10, 50 and 100; moreover where the relationship between variables are quite high, in medium level and quite low were mentioned. RESULTS: Average classification accuracy of simulation results which were carried out 1000 times for each possible condition of trial plan were given as tables. CONCLUSION: It is seen that diagnostic accuracy results increase as the number of independent variables increase. SIMCA method is a method in which the relationship between variables are quite high, the number of independent variables are many in number and where there are outlier values in the data that can be used in conditions having outlier values.