An automated framework for evaluation of deep learning models for splice site predictions.

A novel framework for the automated evaluation of various deep learning-based splice site detectors is presented. The framework eliminates time-consuming development and experimenting activities for different codebases, architectures, and configurations to obtain the best models for a given RNA splice site dataset. RNA splicing is a cellular process in which pre-mRNAs are processed into mature mRNAs and used to produce multiple mRNA transcripts from a single gene sequence. Since the advancement of sequencing technologies, many splice site variants have been identified and associated with the diseases. So, RNA splice site prediction is essential for gene finding, genome annotation, disease-causing variants, and identification of potential biomarkers. Recently, deep learning models performed highly accurately for classifying genomic signals. Convolutional Neural Network (CNN), Long Short-Term Memory (LSTM) and its bidirectional version (BLSTM), Gated Recurrent Unit (GRU), and its bidirectional version (BGRU) are promising models. During genomic data analysis, CNN's locality feature helps where each nucleotide correlates with other bases in its vicinity. In contrast, BLSTM can be trained bidirectionally, allowing sequential data to be processed from forward and reverse directions. Therefore, it can process 1-D encoded genomic data effectively. Even though both methods have been used in the literature, a performance comparison was missing. To compare selected models under similar conditions, we have created a blueprint for a series of networks with five different levels. As a case study, we compared CNN and BLSTM models' learning capabilities as building blocks for RNA splice site prediction in two different datasets. Overall, CNN performed better with [Formula: see text] accuracy ([Formula: see text] improvement), [Formula: see text] F1 score ([Formula: see text] improvement), and [Formula: see text] AUC-PR ([Formula: see text] improvement) in human splice site prediction. Likewise, an outperforming performance with [Formula: see text] accuracy ([Formula: see text] improvement), [Formula: see text] F1 score ([Formula: see text] improvement), and [Formula: see text] AUC-PR ([Formula: see text] improvement) is achieved in C. elegans splice site prediction. Overall, our results showed that CNN learns faster than BLSTM and BGRU. Moreover, CNN performs better at extracting sequence patterns than BLSTM and BGRU. To our knowledge, no other framework is developed explicitly for evaluating splice detection models to decide the best possible model in an automated manner. So, the proposed framework and the blueprint would help selecting different deep learning models, such as CNN vs. BLSTM and BGRU, for splice site analysis or similar classification tasks and in different problems.

Neutrophil-lymphocyte ratio as a mortality predictor for Norwood stage I operations.

BACKGROUND: Hypoplastic left heart syndrome is a lethal congenital heart malformation when untreated resulting in a 95% mortality in the first month of life. In this study, we aimed to investigate the newly introduced inflammatory biomarker, neutrophil-lymphocyte ratio, as a mortality predictor in postoperative hypoplastic left heart syndrome patients. METHODS: Patients were divided into two groups; Group 1 consisted of 33 patients who were discharged and Group 2 including 20 patients who were deceased following surgery. Patients' preoperative demographic characteristics, total white blood cell counts, neutrophil counts, lymphocyte counts, neutrophil-lymphocyte ratio, C-reactive proteins, alanine aminotransferase, aspartate transaminase, urea, and creatinine levels were recorded. Studys' primary endpoint was all-cause patient mortality following surgery. RESULTS: The preoperative neutrophil-lymphocyte ratio was found to be significantly different between the groups (p = 0.001). High neutrophil-lymphocyte ratio was found to be associated with an increased risk of death. The ROC curves of neutrophil-lymphocyte ratio were found to be associated with mortality. The area under curve for the preoperative neutrophil-lymphocyte ratio was 0.74. Neutrophil-lymphocyte ratio predicted mortality with a sensitivity of 78% and a specificity of 65%. CONCLUSION: Neutrophil-lymphocyte ratio can contribute to the early identification of patients at high risk for complications. In addition, through the use of NLR, clinicians could implement measures for the optimal therapeutic approach of cardiac surgery patients and the elimination of adverse patient outcomes.

Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats.

BACKGROUND: Cisplatin (Cis) is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. AIMS: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. STUDY DESIGN: Animal experimentation. METHODS: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection. RESULTS: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhydrase (CA)-II and low carbamoyl phosphate synthetase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. CONCLUSION: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and CA-II enzyme levels.

Evaluation of aortic stiffness in Gilbert syndrome patients: a protective effect of elevated bilirubin levels.

OBJECTIVE: Gilbert's syndrome (GS) is an autosomal recessive disease that is characterized by an increase in indirect bilirubin (IB). The incidence of atherosclerotic heart disease is decreased in GS. This study aimed to investigate the relation between pulse wave velocity (PWV) and the presence of GS. METHODS: The study included 58 GS patients (32 females, age; 27.12 ± 7.27 years, 26 males, age; 26.63 ± 5.84 years) admitted to the internal medicine clinic of the hospital. The control group included 58 healthy individuals (35 females [27.33 ± 8.06 years old, p=0.716] and 23 males [27.38 ± 6.91 years old, p=0.923]). PWV of both groups was measured from the right carotid and femoral arteries. RESULTS: Mean age of the GS group was 26.03 ± 8.22 years, while that of the healthy group was 26.60 ± 5.84 years. The GS group's diastolic blood pressure and PWV were significantly lower than those of the control group: 67.76 ± 8.59 mmHg vs 71.72 ± 7.28 mmHg; p=0.008, and 5.63 ± 1.12 m/s vs 6.18 ± 1.22 m/s; p=0.014 respectively. The GS group's high density lipoprotein (HDL) level was significantly higher than that of the control group: 1.4 ± 0.3 mmol/L vs 1.2 ± 0.3 mmol/L, p=0.029. CONCLUSION: This study found PWV among GS patients to be lower than that among non-smoking and aged-matched healthy controls.

Protective effect of infliximab on methotrexate-induced liver injury in rats: unexpected drug interaction.

AIMS: Although methotrexate (mtx) is a widely used agent to treat cancer and inflammatory diseases, its hepatotoxic effect limits for clinical utility. We aimed to investigate whether infliximab (inf), an inhibitor of tumor necrosis factor-alpha (TNF-α) has a protective effect against mtx-induced hepatotoxicity. MATERIALS AND METHODS: For mtx group, the animals received an intraperitoneal single dose injection of mtx at a dose of 20 mg/kg. For inf group, the animals received an intraperitoneal single dose injection of inf at a dose of 7 mg/kg. For mtx + inf group, the single dose of inf at a dose of 7 mg/kg was given 72 h prior to mtx injection. After 72 h, a single dose of mtx 20 mg/kg was given. All rats were sacrificed 5 days after mtx injection. RESULTS: TNF-α and nitric oxide (NO) levels of mtx group was significantly higher than the control (P < 0.001), inf (P < 0.001) and mtx + inf (P < 0.001) groups. Total score of histological damage was higher in the mtx group when compared with the mtx + inf group. Arginase and carbamoyl phosphate synthetase 1 (CPS-1) of mtx group was suppressed in comparison with the control group and was markedly increased in mtx + inf group. CONCLUSION: Inf may partially prevent mtx-induced hepatic damage in rats. However, the combined usage of mtx and inf increases arginase and CPS-1 enzyme activities and at the same time blocks TNF-α. This combination especially in cancer patients may lead to cancer cell invasion and metastasis.

Topiramate ameliorates abdominal aorta cross-clamping induced liver injury in rats.

BACKGROUND AND AIM: Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury. MATERIALS AND METHODS: Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure. RESULTS: The I/R group's TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes. CONCLUSION: Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery.

Comparison of standard triple therapy, sequential therapy and moxifloxacin-based triple therapy for Helicobacter pylori infection: Patients' compliance and bacterial eradication rates.

OBJECTIVE: To compare the patients' compliance with and the efficacy of existing treatments for Helicobacter pylori eradication, including moxifloxacin-based triple therapy, sequential treatment and the standard treatment. METHODS: Patients with H. pylori infection were randomly assigned to three therapy groups. The triple therapy (MML) group was given moxifloxacin 400 mg/day, metronidazole 500 mg b.i.d. and lansoprazole 30 mg b.i.d. for 10 days. The sequential treatment (AL-CML) group was administrated amoxicillin 1 g b.i.d. and lansoprazole 30 mg b.i.d. for the first 5 days, followed by clarithromycin 500 mg b.i.d., metronidazole 500 mg b.i.d. and lansoprazole 30 mg b.i.d. for the second 5 days. The standard treatment (CAL) group received amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d. and lansoprazole 30 mg b.i.d. for 14 days. The eradication rates were evaluated by per-protocol (PP) analysis and intention-to-treat (ITT) analysis. RESULTS: The eradication rates were 87.1, 85.9 and 85.2% by PP analysis and 87.1, 84.9 and 84.2% by ITT analysis in the MML, AL-CML and CAL group, respectively, and patients' compliance rates were 98.2, 96.5 and 97.1%, respectively. There were no significant differences in treatment efficacy and compliance rates in the MML, AL-CML and CAL groups (P > 0.05). CONCLUSIONS: The present study revealed that standard triple therapy, sequential therapy and moxifloxacin-based triple therapy are all effective treatment regimens in terms of H. pylori eradication rates and compliance with therapy in Turkey.

Adalimumab ameliorates abdominal aorta cross clamping which induced liver injury in rats.

The aim of this study was to investigate the possible protective effects of adalimumab (ADA) on cell damage in rat liver tissue during ischemia/reperfusion (I/R) injury of infrarenal abdominal aorta. Thirty male Wistar-albino rats were divided into three groups: control, I/R, and I/R+ADA, each group containing 10 animals. Laparotomy without I/R injury was performed in the control group animals. Laparotomy in the I/R group was followed by two hours of infrarenal abdominal aortic cross ligation and then two hours of reperfusion. ADA (50 mg/kg) was administered intraperitoneally as a single dose, to the I/R+ADA group, five days before I/R. The tumor necrosis factor-alpha (TNF-α) (pg/mg protein) and nitric oxide (NO) (µmol/g protein) levels in the I/R group (430.8 ± 70.1, 8.0 ± 1.1, resp.) were significantly higher than those in the I/R+ADA group (338.0 ± 71.6, P = 0.006; 6.3 ± 1.2, P = 0.008) and the control group (345.5 ± 53.3, P = 0.008; 6.5 ± 1.5, P = 0.010, resp.). I/R causes severe histopathological injury to the liver tissue, but ADA leads to much less histopathological changes. ADA treatment significantly decreased the severity of liver I/R injury. ADA pretreatment may have protective effects on experimental liver injury.

The evaluation of relationship between adiponectin levels and epicardial adipose tissue thickness with low cardiac risk in Gilbert`s syndrome: an observational study.

OBJECTIVE: Atherosclerotic heart diseases are less frequently seen in patients with Gilbert's syndrome (GS). We aimed to investigate whether serum adiponectin (APN) and epicardial adipose tissue (EAT) thickness have an effect beside the antioxidant effect of bilirubin in lowering the incidence of the atherosclerotic process. METHODS: Sixty-eight patients diagnosed with GS (39 females and 29 males) who had applied at the internal medicine clinic of the hospital were included in this cross-sectional, observational study. The control group included 63 healthy people (39 females and 24 males). EAT thickness was measured by echocardiography. The serum APN levels were also checked. Statistical analysis was performed by using independent sample t-test, Pearson correlation and linear regression analyses. RESULTS: The mean age of the GS group was 28 ± 9 years, and the average EAT thickness was found to be 2.5 ± 0.1 mm. The mean age of the control group was 26 ± 6 years, and the average EAT thickness was found to be 4.2 ± 0.5 mm. When comparing the two groups, the EAT thickness of the GS group was found to be significantly lower (p<0.001) than that of the control group. In the GS group the APN was 14.9 ± 4.2 mg/L, and in the control group the APN was 12.6 ± 4.5 mg/L (p<0.022). We found that total bilirubin (ß=-1,607, p<0,001) and indirect bilirubin (ß=1,086, p<0,001) have an independent association with decreased EAT thickness. CONCLUSION: EAT thickness is associated with coronary atherosclerosis. Low EAT thickness may be related with low release of proinflammatory cytokine. High levels of APN may be related high anti-inflammatory effect. Therefore, low EAT thickness and high levels of APN may demonstrate protective effect on atherosclerotic heart diseases in GS patients.

Cost of acute ischemic and hemorrhagic stroke in Turkey.

OBJECTIVE: The aim of this study is to examine the direct medical costs and outcomes of patients with stroke. MATERIAL AND METHODS: The records of the patients admitted with ischemic and hemorrhagic stroke to the University of Trakya, School of Medicine, Department of Neurology were reviewed retrospectively in year 2007. Direct medical costs (total costs, radiological, laboratory, medicine, and other) were calculated, additionally cost per life saved and per life-year saved were calculated for stroke patients. RESULTS: The study group consisted of 328 patients (169 male/159 female) and mean age was 66.5 ± 12.4 years. Length of hospital stay was 10.7 ± 7.5 days. Mortality rate was 20.4% and the mRS score of the patients was 3.2 ± 2.1. The average cost of stroke was US$ 1677 ± 2964 (29.9% medicine, 19.9% laboratory, 12.8% neuroimaging, and 38% beds and staff). Cost per life saved and per life-year saved were US$ 2108 and US$ 1070, respectively. CONCLUSION: This is the first study in order to determine direct medical cost of stroke in Turkey, therefore, it may be guideline for disease-cost management of stroke.

Usefulness of serum pepsinogen levels as a screening test for atrophic gastritis and gastric cancer.

OBJECTIVE: The purpose of our study was to research the applicability of measuring serum pepsinogen I (PG I) and PG I/pepsinogen II (PG II) ratios as screening tests for atrophic gastritis, which is the most important predisposition for stomach cancer. MATERIALS AND METHODS: We measured serum pepsinogen levels in non-specific gastritis, atrophic gastritis and gastric cancer using a radioimmunoassay method. We included in this study 30 healthy control, 30 nonspecific gastritis, 30 atrophic gastritis and 50 gastric cancer cases. RESULTS: The serum PG I level was statistically higher in the control group and in the patient group with chronic nonspecific gastritis compared to the patient groups with chronic atrophic gastritis and stomach cancer (p<0.05). The best cutoff values for diagnosing stomach cancer using serum PG I and PG I / PG II ratios were found to be <25 ng/ml for PG I and <3.0 for PG I / PG II. The same cut-off values were also most effective for the patients with atrophic gastritis. CONCLUSIONS: Serum pepsinogen screening was shown to be a practical predictor of stomach cancer and atrophic gastritis, the most important predisposing lesion for stomach cancer. Although the diagnosis of stomach cancers localized in the pylorus and cardia via this method is difficult, we believe that the detection of early-stage cancers that develop following chronic atrophic gastritis in particular will be possible, and therefore the morbidity and mortality of stomach cancer will be decreased.

Bilateral basal ganglionic lesions due to transdermal methanol intoxication.

Methanol is a clear, colorless, and highly toxic liquid with a similar smell and taste to ethanol, and is found in many commercial products such as solvents and cleaning fluids. Severe methanol intoxication occurs after suicidal or accidental oral ingestion of solvents. A few patients with methanol intoxication via the transdermal route have been reported. We present a 47-year-old woman with acute transdermal methanol intoxication admitted to the emergency department with weakness, blurred vision, bilateral areactive mydriasis, and deterioration of consciousness.

Stroke due to bee sting.

Although bee stings can cause local reactions, neurovascular complications are rare. A 60-year-old man developed a focal neurologic deficit 2 hours after multiple bee stings, which was confirmed to be acute cerebral infarctions on magnetic resonance imaging scan.

Effects of the myeloperoxidase 463 gene polymorphisms on development of atrophy in H pylori infected or noninfected gastroduodenal disease.

AIM: To investigate the relationship between myelo-peroxidase polymorphisms as a host-related factor and atrophy caused by H pylori. METHODS: Our study enrolled 77 patients. Biopsy materials obtained during gastrointestinal endoscopies were evaluated for the presence of H pylori. Polymerase chain reaction-restriction fragment length polymorphism assay was used to characterize myeloperoxidase genotypes. RESULTS: Forty four patients (57.1%) were Hp (+) and 33 (42.9%) were Hp (-). Sixty six (85.7%) had GG genotype, 10 (12.9%) had GA genotype and 1 (1.29%) had AA genotype. The change in atrophy in relation to neutrophil infiltration was significant in Hp (+) patients (P = 0.0001). The change in atrophy in relation to neutrophil infiltration in patients with GG genotype was significant (P = 0.002). However, the change in atrophy in relation to neutrophil infiltration was not significant in patients with Hp (+) GG genotype (r = 0.066, P = 0.63). CONCLUSION: Myeloperoxidase genotype is critical for development of atrophy in relation to the severity of inflammation. However, it is interesting to note that, H pylori does not show any additive effect on development of atrophy.

A comparison of glycemic effects of glimepiride, repaglinide, and insulin glargine in type 2 diabetes mellitus during Ramadan fasting.

Although diabetics may be exempted from Ramadan fasting, many patients still insist on this worship. Aim of the present study is to compare the effects of glimepiride, repaglinide, and insulin glargine in type 2 diabetics during Ramadan fasting on the glucose metabolism. Patients, who were willing to fast, were treated with glimepiride (n=21), repaglinide (n=18), and insulin glargine (n=10). Sixteen non-fasting control type 2 diabetics matched for age, sex, and body mass index were also included. Fasting blood glucose (FBG), post-prandial blood glucose (PBG), HbA1c, and fructosamine as well as lipid metabolism were evaluated in pre-Ramadan, post-Ramadan, and 1-month post-Ramadan time points. There was no significant change from pre-Ramadan in FBG, PBG, and HbA1c variables in fasting diabetics at post-Ramadan and 1-month post-Ramadan. However, PBG was found higher in non-fasting control diabetics at post-Ramadan and 1-month post-Ramadan (p<0.05 and p<0.001, respectively). In fructosamine levels, a significant increase was noted both in fasting group and non-fasting group at 1-month post-Ramadan (p<0.01 for all). However, no significant difference was found in the comparison of the changes in fructosamine levels between fasting group and non-fasting group. Risk of hypoglycemia did not significantly differ between fasting and non-fasting diabetics. There was no significant difference between three drug therapies regarding glucose metabolism and rate of hypoglycemia. No adverse effects on plasma lipids were noted in fasting diabetics. In this fasting sample of patients with type 2 diabetes, glimepiride, repaglinide, and insulin glargine did not produce significant changes in glucose and lipid parameters.

Comparison of palpation-guided fine-needle aspiration biopsy to ultrasound-guided fine-needle aspiration biopsy in the evaluation of thyroid nodules.

OBJECTIVE: Although fine-needle aspiration biopsy (FNAB) of thyroid nodules is a reliable and simple method, the diagnostic value may be limited by inadequate and false-negative results. In this prospective study, we compared palpation-guided FNAB (PGFNAB) with ultrasound-guided FNAB (UGFNAB) to establish the rates of inadequate material and cost-effectiveness. DESIGN: A total of 285 thyroid nodules in 215 patients were included in the study. Palpable nodules with the greatest diameter between 1 and 2.5 cm were included in the study. PGFNAB and UGFNAB techniques were applied to the same nodule by the same operator. Cytologic evaluations were performed by the same cytologist in a blinded fashion. To provide cost analysis, the prices obtained from different hospitals were evaluated. MAIN OUTCOME: The rates of inadequate material for PGFNAB and UGFNAB were significantly different as 32.3% and 21.4%, respectively (p = 0.004). There was significantly higher inadequate material rate in PGFNAB group for small-sized nodules (greatest nodule diameter between 10 and 15 mm) (p = 0.009), despite inadequate material rate was not significant for both procedures for larger sized nodules. False-negative results were 15.8% for PGFNAB and 5.6% for UGFNAB. Regarding cost analysis, the difference between the two methods was 20 dollars on average for each patient. CONCLUSIONS: We consider UGFNAB to be superior to PGFNAB for obtaining adequate material especially for small-sized nodules, as well as providing more accurate cytologic evaluation. Indeed, the difference between the costs of two procedures might be acceptable.

Modified semicircular constricting annuloplasty (Sagban's annuloplasty) in severe functional tricuspid regurgitation: alternative surgical technique and its mid-term results.

OBJECTIVE: De Vega annuloplasty is one of the most effective methods used in surgical correction of functional tricuspid regurgitation (FTR). Physiologic annular motions are protected by De Vega annuloplasty. However, recurrent tricuspid regurgitation secondary to Bowstring (Guitar string) phenomenon may be seen after De Vega annuloplasty as a result of gliding (jiggle) effect. The aim of this new annuloplasty was to prevent Bowstring phenomenon seen in De Vega annuloplasty. METHODS: Twenty-five patients with severe FTR secondary to the left-sided valvular heart disease were included in this study. Modified semicircular constricting annuloplasty (Sagban's annuloplasty): The procedure is performed utilizing 0 and 2-0 polypropylene sutures. At first, 0 and 2-0 polypropylene sutures are fixed and knotted at anteroseptal and posteroseptal comissural regions (named as anchoring points). 2-0 Polypropylene sutures which come from anchoring points in clockwise and counterclockwise direction are used to encircle the free wall annulus as well as 0 polypropylene sutures in spiral fashion (spiral annulary suture technique). When both sutures get to the anteroposterior comissural region (tying point), they are passed through plastic snares. After the annuloplasty is completed, with the heart beating and the pulmonary artery clamped, competency of the valve is tested by injecting saline into the right ventricular chamber before the adjusting suture is tied. In this annuloplasty, 0 polypropylene sutures are used for reduction and constriction, 2-0 polypropylene sutures are used for the fixation of 0 polypropylene sutures in annular level. RESULTS: FTR improved totally in 16 patients (66.7%), 4 patients (16.7%) had first degree, 3 patients (12.5%) had second degree, and only 1 patient (4.2%) had third degree residual tricuspid regurgitation in an average follow-up period of 17.8 months. One patient died from low cardiac output in early postoperative period. CONCLUSION: There is no risk of recurrent regurgitation secondary to Bowstring phenomenon in this alternative annuloplasty technique and this annuloplasty is cost-effective and performed easily.

Serum lipids, lipoproteins and apolipoproteins levels in patients with nonalcoholic steatohepatitis.

GOALS/BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver disease that is histologically indistinguishable from alcoholic hepatitis but occurs in persons who do not consume alcohol in excess. The objectives of this study are to measure serum levels of lipids, lipoproteins and apolipoproteins (apo AI, apo B), lipoprotein (a) [Lp (a)] in patients with nonalcoholic steatohepatitis (NASH), and to investigate the relationship with liver histology. STUDY: The scope of this study is composed of 36 patients (27 males, 9 females) with NASH, diagnosed by biochemical liver function tests, sonographic examination of liver and liver biopsy and 32 healthy adults as a control group (22 males, 10 females). Serum lipids, lipoproteins and apo AI, apo B, and Lp (a) measurements were taken in the study group and controls, and a correlation with histopathologic findings was searched for. RESULTS: Serum mean levels (+/- SD as mg/dl) of total cholesterol (201.05 +/- 34.48), triglyceride (225.94 +/- 156.50), and LDL-cholesterol (111.77 +/- 19.85) in patients with NASH were significantly higher than those of the control group (170.68 +/- 31.06; 138.81 +/- 49.96; 100.68 +/- 17.98; respectively) and serum HDL-cholesterol level (41.22 +/- 2.47) was less than that of the control group (45.06 +/- 8.32) (P = 0.017). The serum mean level of apo AI (151.54 +/- 30.90) in the study group was lower than that of the controls (160.62 +/- 22.11), but the difference was not significant (P = 0.17). However, the serum apo AI level in patients with liver fibrosis (140.62 +/- 35.62) was significantly lower than that of patients without liver fibrosis (164.57 +/- 25.47) (P = 0.01). The serum mean level of apo B (89.80 +/- 20.62) in the patients was significantly higher than the control group (73.25 +/- 25.39) (P = 0.004), but not correlate with liver histopathology. The serum Lp (a) levels in both the patients (13.09 +/- 9.61) and the controls (12.01 +/- 7.50) were not different (P = 0.61). Hypertriglyceridemia (above 220 mg/dL) had a positive correlation with steatosis of the liver (r = 0.333, P = 0.04) and a negative correlation with liver fibrosis (r = -0.438, P = 0.008). There was a significant negative correlation between apo AI and steatosis (r = -0.360, P = 0.03), inflammation (r = -0.364, P = 0.03) and fibrosis of liver (r = -0.418, P = 0.01). A positive correlation of serum LDL-cholesterol (r = 0.507, P = 0.002) and Lp(a) (r = 0.394, P = 0.01) concentrations with liver fibrosis was also noted. CONCLUSIONS: Abnormalities of lipid metabolism such as the increase of serum triglyceride, cholesterol and LDL-cholesterol level and decrease of HDL-cholesterol may be the contributing factors in the development of NASH. The decrease in apo AI and the increase in LDL and Lp (a) in patients were correlated with liver fibrosis. Apo AI may be a serum marker for liver fibrosis in patients with NASH.

Serum ubiquitin levels in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis is increasingly recognized as the most common liver disease in patients with elevated liver enzymes. In the pathophysiology of nonalcoholic steatohepatitis, the first step is the lipid accumulation in the liver causing steatosis, the second step involves the endotoxins, cytokines and environmental toxins causing oxidative stress and lipid peroxidation, in time leading to steatohepatitis. Ubiquitin is a molecular chaperone that plays a major role in the degradation of intracellular proteins. Ubiquitin proteasome system is also considered as a cellular defense mechanism that removes damaged proteins generated by oxidative stress. In order to search for the role of ubiquitin in the pathogenesis of nonalcoholic steatohepatitis, serum levels of ubiquitin were studied in patients with nonalcoholic steatohepatitis for the first time in the literature, to our knowledge. METHODOLOGY: Eighteen patients with biopsy proven nonalcoholic steatohepatitis diagnosis (13 males and 5 females with a mean age of 41) and 16 healthy volunteers as a control group (11 males and 5 females, with a mean age of 38) were included in the study. Serum ubiquitin levels were studied by ELISA method. RESULTS: The mean serum ubiquitin level (14.13 +/- 1.46 micrograms/mL) in patients with nonalcoholic steatohepatitis was significantly elevated compared to that of the control group (7.66 +/- 0.40 micrograms/mL) (p < 0.001). No correlation was found among serum ubiquitin levels and hepatic steatosis, inflammation and fibrosis. CONCLUSIONS: Increased serum ubiquitin levels may show that the ubiquitin proteasome pathway actively participates in defending against oxidative stress in nonalcoholic steatohepatitis. Serum ubiquitin concentration may be a marker predicting the intracellular cytoprotective response against oxidative stress rather than the degree of liver damage in pathogenesis of nonalcoholic steatohepatitis. Ubiquitin proteasome system based therapies may have a place in the treatment of patients with nonalcoholic steatohepatitis in the future.

Relationship between thyroid autoimmunity and Yersinia enterocolitica antibodies.

It has previously been proposed that subclinical Yersinia enterocolitica infection may play a role in autoimmune thyroid disease (AITD). In this study, we investigated the relationship between the thyroid autoantibodies and the antibodies that produced against different serotypes of Y. enterocolitica. A total of 215 subjects were included into the study (65 newly diagnosed Graves' disease [GD], 57 Hashimoto's thyroiditis [HT], 53 nontoxic diffuse goiter [NTDG], and 40 subjects for control group [CG]). Thyroid receptor antibodies (TRAb), thyroid and agglutinating antibodies against Y. enterocolitica serotype O:3, O:5, O:8, O:9 were measured in the blood samples. The highest incidence of Y. enterocolitica antibody positivity was measured in GD (53.8% for O:3, 29.2% for O:5, 44.6% for O:8, and 40% for O:9) and followed by HT. In patients with GD, TRAb levels were also higher than in patients with HT, NTDG, and CG. There was no difference between NTDG and CG in respect to the titer levels and the positivity of both TRAb and Y. enterocolitica antibodies. There was also a weak linear correlation between TRAb level and the titer of antibodies against Y. enterocolitica antigens. It can be concluded that Y. enterocolitica infection may play a role in etiology of GD in Turkey.