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A report on a modified magnetic tunnel transistors having a silicon tunnel emitter is presented. The device has the structure Si/Al2O3/base/Si with a spin-valve metal base, a Schottky barrier collector, but a silicon emitter separated from the base by a thin tunnel oxide.

The fabrication and electrical characterization of epitaxial Schottky diodes of a half-metallic ferromagnet on an oxide semiconductor is examined. The Schottky barrier height is found to be 0.95 eV (0.65 eV) and the ideality factor is 1.08 (1.18) for the diodes with a low (high) doped semiconductor at room temperature.

The spin-dependent hot-electron transport and local magnetic switching of ferromagnetic thin films grown on a Au/Si(100) collector is examined with ballistic electron magnetic microscopy. The change in the relative magnetization of the ferromagnetic layers from parallel to antiparallel leads to a decline in the collector current by a factor of 5 for Ni80Fe20/Au/Co spin valves.

The electrical properties of silicon-based spin-valve transistors are examined. Results indicate the presence of magentocurrent of 400 percent in spin-valve transistors and high output current of 40 muA.

Ballistic electron magnetic microscopy is used to study spin-dependent hot-electron transport and local magnetic switching of ferromagnetic thin films grown on a Au/Si(100) collector. For Ni80Fe20 films, the collector current is a factor of 2 larger than for Co, consistent with the shorter hot-electron attenuation length of Co. For Ni80Fe20/Au/Co spin valves, the collector current is reduced by a factor of 5 when the relative magnetization of the ferromagnetic layers changes from parallel to antiparallel. By sweeping the applied magnetic field, we obtain nanoscale hysteresis loops, where the hot electrons are collected from an area of about 10 nm. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The electrical characteristics of silicon-based spin-valve transistors are reported, focusing on how the output current and magnetocurrent depend on the magnitude of the emitter current. Transistors with a different combination of Schottky barriers (Si/Au and Si/Cu) were used. The collector current rapidly increases with emitter current, without significant loss of magnetocurrent. Spin-valve transistors with magnetocurrent around 400% and high output current up to 40 μA are obtained. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Cryo-EM and X-ray crystallography provide crucial experimental data for obtaining atomic-detail models of biomacromolecules. Refining these models relies on library-based stereochemical restraints, which, in addition to being limited to known chemical entities, do not include meaningful noncovalent interactions relying solely on nonbonded repulsions. Quantum mechanical (QM) calculations could alleviate these issues but are too expensive for large molecules. We present a novel AI-enabled Quantum Refinement (AQuaRef) based on AIMNet2 neural network potential mimicking QM at substantially lower computational costs. By refining 41 cryo-EM and 30 X-ray structures, we show that this approach yields atomic models with superior geometric quality compared to standard techniques, while maintaining an equal or better fit to experimental data., Competing Interests: Competing Interests The authors declare no competing interests.

Hereditary hemochromatosis (HH) is an autosomal recessive inherited iron-loading disorder and is characterized by chronic hepatitis, cirrhosis, diabetes, and bronze skin. The hemochromatosis gene (C282Y homozygosity)-related hemochromatosis is the most common form of HH. The prevalence of HH is varied. Here, we defined six cases with C282Y homozygosity-related HH in a single center in Turkiye., Competing Interests: The authors have no conflict of interest to declare.

Objectives: The aims of the present study were to investigate a combination of magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE) or MRE and fibrosis score 4 (FIB-4) in the detection of significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Methods: Between November 5, 2021, and March 4, 2022, a total of 119 consecutive patients with MASLD were included. Liver stiffness was measured using liver biopsy, MRE, VCTE, and FIB-4. Data were collected from outpatient visit charts. Significant fibrosis was defined as ≥ stage 2 fibrosis., Results: All 119 MASLD patients were Caucasian, and their median age was 55 years. MRE, VCTE, and FIB-4 demonstrated significant accuracy in the detection of significant fibrosis with an area under the ROC curve (AUC) of 0.848 ± 0.036 (p < 0.001), 0.632 ± 0.052 (p = 0.012), and 0.664 ± 0.051 (p = 0.001), respectively. However, the diagnostic performance of MRE was superior compared to that of VCTE (AUC difference: 0.216 ± 0.053, p < 0.001) and FIB-4 (AUC difference: 0.184 ± 0.058, p = 0.001). With logistic regression analysis, it was determined that when compared to MRE alone, a combination of MRE and TE (p = 0.880) or MRE and FIB-4 (p = 0.455) were not superior for detecting significant fibrosis., Conclusions: MRE alone is an accurate and non-invasive method for the identification of MASLD patients with significant fibrosis., Clinical Relevance Statement: Magnetic resonance elastography alone accurately detects significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease., Key Points: • In routine clinical practice, several non-invasive biochemical-based biomarkers and imaging methods are widely used to assess liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • Magnetic resonance elastography (MRE) is more accurate than vibration-controlled transient elastography (VCTE) or fibrosis score 4 (FIB-4) for assessing liver fibrosis and identifying significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • The combination of MRE and VCTE or MRE and FIB-4 was not superior to MRE alone., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Aim: This study aimed to identify the indications for liver transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT., Materials and Methods: We conducted a multicenter cross-sectional observational study across 11 tertiary centers in Turkiye from 2010 to 2020. The study included 5,080 adult patients., Results: The mean age of patients was 50.3±15.2 years, with a predominance of female patients (70%). Chronic viral hepatitis (46%) was the leading etiological factor, with Hepatitis B virus infection at 35%, followed by cryptogenic cirrhosis (24%), Hepatitis C virus infection (8%), and alcohol-related liver disease (ALD) (6%). Post-2015, there was a significant increase in both the number of liver transplants and the proportion of living donor liver transplants (p<0.001). A comparative analysis of patient characteristics before and after 2015 showed a significant decline in viral hepatitis-related LT (p<0.001), whereas fatty liver disease-related LT significantly increased (p<0.001)., Conclusion: Chronic viral hepatitis continues to be the primary indication for LT in Turkiye. However, the proportions of non-alcoholic fatty liver disease (NAFLD) and ALD-related LT have seen an upward trend over the years., Competing Interests: The authors have no conflict of interest to declare., (© Copyright 2024 by Hepatology Forum.)

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against COVID-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments., (© 2023 The Authors. Molecular Informatics published by Wiley-VCH GmbH.)

Background: Pyruvate dehydrogenase complex deficiency (PDCD) is a mitochondrial neurometabolic disorder of energy deficit, with incidence of about 1 in 42,000 live births annually in the USA. The median and mean ages of diagnosis of PDCD are about 12 and 31 months, respectively. PDCD is a major cause of primary lactic acidosis with concomitant elevation in blood alanine (Ala) and proline (Pro) concentrations depending on phenotypic severity. Alanine/Leucine (Ala/Leu) ≥4.0 and Proline/Leucine (Pro/Leu) ≥3.0 combination cutoff from dried blood spot specimens was used as a biomarker for early identification of neonates/infants with PDCD. Further investigations were needed to evaluate the sensitivity (SN), specificity (SP), and clinical utility of such amino acid (AA) ratio combination cutoffs in discriminating PDCD from other inborn errors of metabolism (IEM) for early identification of such patients., Methods: We reviewed medical records of patients seen at UPMC in the past 11 years with molecularly or enzymatically confirmed diagnosis. We collected plasma AA analysis data from samples prior to initiation of therapeutic interventions such as total parenteral nutrition and/or ketogenic diet. Conditions evaluated included organic acidemias, primary mitochondrial disorders (MtDs), fatty acid oxidation disorders (FAOD), other IEMs on current newborn screening panels, congenital cardiac great vessel anomalies, renal tubular acidosis, and non-IEMs. The utility of specific AA ratio combinations as biomarkers were evaluated using receiver operating characteristic curves, correlation analysis, principal component analysis, and cutoff SN, SP, and positive predictive value determined from 201 subjects with broad age range., Results: Alanine/Lysine (Ala/Lys) and Ala/Leu as well as (Ala + Pro)/(Leu + Lys) and Ala/Leu ratio combinations effectively discriminated subjects with PDCD from those with other MtDs and IEMs on current newborn screening panels. Specific AA ratio combinations were significantly more sensitive in identifying PDCD than Ala alone or combinations of Ala and/or Pro in the evaluated cohort of subjects. Ala/Lys ≥3.0 and Ala/Leu ≥5.0 as well as (Ala + Pro)/(Leu + Lys) ≥2.5 and Ala/Leu ≥5.0 combination cutoffs identified patients with PDCD with 100% SN and ~85% SP., Conclusions: With the best predictor of survival and positive cognitive outcome in PDCD being age of diagnosis, PDCD patients would benefit from use of such highly SN and SP AA ratio combination cutoffs as biomarkers for early identification of at-risk newborns, infants, and children, for early intervention(s) with known and/or novel therapeutics for this disorder., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC)., Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study., Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed., Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC., Competing Interests: The authors have no conflict of interest to declare., (© Copyright 2023 by Hepatology Forum.)

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists., Competing Interests: The authors have no conflict of interest to declare., (© Copyright 2023 by Hepatology Forum.)

Background and Aims: The aim of the present study was to determine incident cases of extrahepatic malignancy in patients with nonalcoholic fatty liver disease (NAFLD) and to identify whether the factors are associated with cancer development., Methods: Between 15 January 2001 and 14 March 2021, a total of 1365 patients had been diagnosed with NAFLD were enrolled in the study., Results: The median follow-up period was 59.5 months. The mean age was 50.9 ± 10.9 years. The female gender was predominant (57%). During the follow-up period, 62 extrahepatic malignancies and 11 hepatocellular carcinomas were identified. Of all extrahepatic malignancies, 51 were solid organ malignancies and 11 were hematological malignancies. Female breast cancer was the most frequent (25.8%), followed by thyroid cancer (19.4%), lymphoma (12.9%), and lung cancer (9.7%). In univariate and multivariable analyses, after adjusting for age and sex, the presence of diabetes and high initial baseline gamma glutamyl transpeptidase (GGT) levels were significantly associated with the development of extrahepatic malignancies [hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.04-3.20, P = 0.036] and HR = 1.96, 95% CI: 1.14-3.38, P = 0.015, respectively). In 424 biopsy-proven NAFLD patients, the development of extrahepatic cancer was significantly associated with the severity of hepatic fibrosis (HR = 3.31, 95% CI: 1.36-8.07; P = 0.008)., Conclusion: Extrahepatic malignancies are frequently seen in patients with NAFLD. Diabetes mellitus, high baseline GGT levels, and significant hepatic fibrosis are associated with the development of extrahepatic cancer in patients with NAFLD., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors have no conflict of interest to declare.

Pyruvate dehydrogenase complex (PDC) deficiency is a major cause of primary lactic acidemia resulting in high morbidity and mortality, with limited therapeutic options. The E1 component of the mitochondrial multienzyme PDC (PDC-E1) is a symmetric dimer of heterodimers (αβ/α'β') encoded by the PDHA1 and PDHB genes, with two symmetric active sites each consisting of highly conserved phosphorylation loops A and B. PDHA1 mutations are responsible for 82-88% of cases. Greater than 85% of E1α residues with disease-causing missense mutations (DMMs) are solvent-inaccessible, with ∼30% among those involved in subunit-subunit interface contact (SSIC). We performed molecular dynamics simulations of wild-type (WT) PDC-E1 and E1 variants with E1α DMMs at R349 and W185 (residues involved in SSIC), to investigate their impact on human PDC-E1 structure. We evaluated the change in E1 structure and dynamics and examined their implications on E1 function with the specific DMMs. We found that the dynamics of phosphorylation Loop A, which is crucial for E1 biological activity, changes with DMMs that are at least about 15 Å away. Because communication is essential for PDC-E1 activity (with alternating active sites), we also investigated the possible communication network within WT PDC-E1 via centrality analysis. We observed that DMMs altered/disrupted the communication network of PDC-E1. Collectively, these results indicate allosteric effect in PDC-E1, with implications for the development of novel small-molecule therapeutics for specific recurrent E1α DMMs such as replacements of R349 responsible for ∼10% of PDC deficiency due to E1α DMMs.

The behavior of proteins is closely related to the protonation states of the residues. Therefore, prediction and measurement of p K a are essential to understand the basic functions of proteins. In this work, we develop a new empirical scheme for protein p K a prediction that is based on deep representation learning. It combines machine learning with atomic environment vector (AEV) and learned quantum mechanical representation from ANI-2x neural network potential (J. Chem. Theory Comput. 2020, 16, 4192). The scheme requires only the coordinate information of a protein as the input and separately estimates the p K a for all five titratable amino acid types. The accuracy of the approach was analyzed with both cross-validation and an external test set of proteins. Obtained results were compared with the widely used empirical approach PROPKA. The new empirical model provides accuracy with MAEs below 0.5 for all amino acid types. It surpasses the accuracy of PROPKA and performs significantly better than the null model. Our model is also sensitive to the local conformational changes and molecular interactions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

Background and Aim: The objective of the present study was to investigate the prevalence of metabolic-associated fatty liver disease (MAFLD) in patients with dyspepsia., Materials and Methods: A total of 909 consecutive patients who presented with dyspepsia at 8 tertiary care centers in Turkey between March 2019 and December 2019 were included., Results: The median age was 47 years. Among them, 30.3% of the patients were obese, 18.8% had type 2 diabetes mellitus (T2DM), 35.1% had metabolic syndrome, 84.8% had dyslipidemia, and 23.9% had hypertension. The prevalence of MAFLD was 45.5%. Among the patients with MAFLD, the prevalence of obesity, T2DM, metabolic syndrome, dyslipidemia, and hypertension was 43.3%, 24.9%, 52.5%, 92.3%, and 31.9%, respectively. MAFLD was significantly associated with all of the metabolic comorbidities (p<0.001). The median Fibrosis-4 Index score of the MAFLD patients was 0.88 (range: 0.1-9.5). Of note, 53 patients with hepatic steatosis did not meet the MAFLD criteria., Conclusion: The results of the present study indicated that there was a significantly high prevalence of MAFLD observed in daily clinical practice in Turkey. Early diagnosis and prevention efforts should be implemented to reduce disease progression, and a region-based strategy is recommended., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© Copyright 2021 by Hepatology Forum - Available online at www.hepatologyforum.org.)

Background and Aim: Chronic liver disease is a risk factor for osteoporosis, osteopenia and bone fractures. In this study, prevalence and risk factors of osteoporosis and vitamin D deficiency and also their effects on survival were investigated in 218 patients with chronic liver disease., Materials and Methods: Prevalence of osteoporosis and vitamin D levels was calculated. Risk factors for osteoporosis (gender, age, body mass index, etiology), serum bilirubin, albumin, 25-hydroxy (OH) vitamin D, parathyroid hormone levels, bone mineral density (BMD) with DEXA, bone formation (osteocalcin) and bone resorption (type 1 collagen) levels, Model for End-Stage Liver Disease (MELD) Na and Child-Pugh (CP) score were recorded. The effects of vitamin D levels and BMD on survival were evaluated., Results: One hundred forty-seven (67.4%) patients were female (mean age, 50.4±11.7). Patients were Child A by 40.8%, Child B by 47.1%, and Child C by 12.1%. Mean MELD Na score was 8.4±2.8. Data of the BMD were established in 218 patients and 25-OH D levels in 122 patients. Mean serum 25-OH D level was 14.26±9.44 ng/mL. Osteoporosis was identified in 42 (19.3%) and osteopenia in 115 (52.8%) patients, according to BMD. Osteocalcin levels and collagen type 1 levels were high in 25.6% and 12.5% of patients, respectively. No statistically difference was found, including gender (p=0.69), age (p=0.38), etiology (p=0.16), BMI (p=0.32), CP score (p=0.42), MELD (0.14), albumin (p=0.11), total bilirubin (p=0.99), Ca (0.67), PTH (0.88), osteocalcin (0.92), collagen type 1(p=0.25) between osteoporotic and non-osteoporotic patients. Patients were followed-up for a median of 30.07±11.83 months after BMD measurement. Fifty-four (24.8%) patients died during the follow-up period, none of them are related to bone fracture. There was no statistically difference on survival between osteoporosis group (32.2±2.3 months) and non-osteoporosis group (37.2±1.7 months; p=0.26) or when patients with 25-OH D 3 ≤10 ng/mL were compared to patients with 25-OH D 3 >20 ng/mL (34.4±2.0 months vs. 39.1±1.6 months, p=0.308)., Conclusion: In conclusion, the prevalence of bone disease was found to be higher in cirrhotic patients. Although osteoporosis and vitamin D deficiency were found to decrease survival, this effect was not statistically significant. We suggest designing multi-institutional and/or multinational studies with larger and more heterogenous patient groups would enable better testing of this phenomenon., Competing Interests: The authors do not have any conflict of interest., (© Copyright 2020 by Hepatology Forum.)

Competing Interests: The authors do not have any conflict of interest.

The ring-shaped sliding clamp proteins have crucial roles in the regulation of DNA replication, recombination, and repair in all organisms. We previously showed that the Escherichia coli β-clamp is dynamic in solution, transiently visiting conformational states in which Domain 1 at the dimer interface is more flexible and prone to unfolding. This work aims to understand how the stability of the dimer interface influences clamp-opening dynamics and clamp loading by designing and characterizing stabilizing and destabilizing mutations in the clamp. The variants with stabilizing mutations conferred similar or increased thermostability and had similar quaternary structure as compared to the wild type. These variants stimulated the ATPase function of the clamp loader, complemented cell growth of a temperature-sensitive strain, and were successfully loaded onto a DNA substrate. The L82D and L82E I272A variants with purported destabilizing mutations had decreased thermostability, did not complement the growth of a temperature-sensitive strain, and had weakened dimerization as determined by native trapped ion mobility spectrometry-mass spectrometry. The β L82E variant had a reduced melting temperature but dimerized and complemented growth of a temperature-sensitive strain. All three clamps with destabilizing mutations had perturbed loading on DNA. Molecular dynamics simulations indicate altered hydrogen-bonding patterns at the dimer interface, and cross-correlation analysis showed the largest perturbations in the destabilized variants, consistent with the observed change in the conformations and functions of these clamps., (Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Semi-empirical quantum methods from the neglect of differential diatomic overlap (NDDO) family such as MNDO, AM1, or PM3 are fast albeit approximate quantum methods. By combining them with linear scaling methods like the divide & conquer (D&C) method, it is possible to quickly evaluate the energy of systems containing hundreds to thousands of atoms. We here present our implementation in the Amber biomolecular package of a SEBOMD module that provides a way to run semi-empirical Born-Oppenheimer molecular dynamics. At each step of a SEBOMD, a fully converged self-consistent field (SCF) calculation is performed to obtain the semiempirical quantum potential energy of a molecular system encaged or not in periodic boundary conditions. We describe the implementation and the features of our SEBOMD implementation. We show the requirements to conserve the total energy in NVE simulations, and how to accelerate SCF convergence through density matrix extrapolation. Specific ways of handling periodic boundary conditions using mechanical embedding or electrostatic embedding through a tailored quantum Ewald summation is developed. The parallel performance of SEBOMD simulations using the D&C scheme are presented for liquid water systems of various sizes, and a comparison between the traditional full diagonalization scheme and the D&C approach for the reproduction of the structure of liquid water illustrates the potentiality of SEBOMD to simulate molecular systems containing several hundreds of atoms for hundreds of picoseconds with a quantum mechanical potential in a reasonable amount of CPU time.

Background and Objective: Bismuth salts are used for treating dyspepsia, and they exert antibacterial effects on Helicobacter pylori. This study aimed to compare the efficacy and safety of three bismuth-containing combination regimens for H. pylori eradication in a Turkish population., Methods: In this single-center study, 149 patients, who were diagnosed with H. pylori infection with urea breath test and histopathological examination, were randomized to receive the following therapies for 14 days: (1) bismuth-containing clarithromycin-based triple therapy (CBS-LAC), (2) bismuth-containing levofloxacin-based triple therapy (CBS-LAL), and (3) bismuth-containing quadruple therapy (BCQT). Eradication rates were evaluated six weeks after the treatment by performing intention to treat (ITT) and per protocol (PP) analyses. In addition, data on side effect profiles and patient compliance were collected., Results: PP and ITT analyses showed that eradication rates were 86% and 81.1%, respectively, with BCQT; 68.3% and 66.7%, respectively, with CBS-LAL therapy; and 65.3% and 59.3%, respectively, with CBS-LAC therapy. Eradication rates obtained using PP and ITT analyses were statistically significant for all the regimens., Conclusion: Addition of bismuth to standard triple and levofloxacin-based regimen did not show an acceptable increase in eradication rates. Therefore, BCQT may be preferred for the first-line treatment of H. pylori infection., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide, with an incidence equal to the death rate., Material and Methods: We aimed to detect the prognostic factors for HCC patients. We retrospectively analyzed 12 years data of 115 patients who have biopsy-proven HCC. Clinical and demographic characteristics of patients with treatment modalities, survival rates, and prognostic factors were analyzed., Results: There were 93 male patients, and the mean age was 63.5±11.8 years. Most patients had cirrhosis due to hepatitis virus infection. Median follow-up time was 17 months (1 month-9.5 years) after the diagnosis of HCC. The nodule was single in 43 (37.4%) patients, there were 2-3 nodules in 30 (26.1%), and >3 or diffuse nodules in 42 (36.5%) patients. Distribution of treatment modalities was as follows: 23 (20%) patients had liver transplantation, 15 (13%) had HCC resection, 12 patients (10.4%) had radiofrequency ablation (RFA), 26 patients (22.6%) had transarterial chemoembolization (TACE), 2 (1.7%) had alcohol ablation, and 37 patients (32.2%) had no treatment. Tumor sizes of 9 patients (39.1%) in the transplanted group exceeded the Milan criteria. Mean survival was 72±6.9, 78.8 ±12.5, 19.5±2.8, 20.6±4.2, 16.0±5.9 months in those that received transplantation, resection, RFA, TACE, and no treatment, respectively (p<0.001). Survival was significantly poorer in patients >63 years old (p=0.001), with serum albumin level ≤3.4 g/dL (p=0.01), and with diffuse HCC (p<0.001)., Conclusions: Survival was significantly better in patients who underwent liver transplantation or surgical resection. Tumor number, age, and serum albumin level were the most important prognostic factors related to overall survival.

Fractalkine (CX3C), a chemokine expressed by epithelial cells within normal and inflamed colorectal mucosa, induces leukocyte adhesion and migration via fractalkine receptor. The aim of this study was to investigate two single nucleotide polymorphisms of the fractalkine receptor gene as a risk factor both for the development and clinical findings of ulcerative colitis. In this study, 51 patients with ulcerative colitis (UC) and 80 controls were recruited. Genotypes of fractalkine receptorc.745G&gt;A (V249I) and c.839C&gt;T (T280M) polymorphisms were identified by restriction fragment length polymorphism analyses after polymerase chain reaction.Genotype distribution and allele frequencies of V249I and T280M were not statistically significantly different between UC and control groups (p&gt;0.05). No statistically significant relationship was found between fractalkine receptor polymorphisms and clinical findings of UC. We observed no significant difference in fractalkine receptor polymorphism between patients and control group and no genotype-phenotype relation. Therefore, we concluded that fractalkine receptor polymorphisms may not contribute to the molecular pathogenesis of UC.

Background and Objective: To investigate the presence of any possible association between H. pylori density in the stomach and the efficacy of triple (lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1g b.i.d. for 14 days) and bismuth-containing quadruple (colloidal bismuth subcitrate 300 mg q.i.d., lansoprazole 30 mg b.i.d., tetracycline 500 mg q.i.d. and metronidazole 500 mg t.i.d. for 14 days) eradication therapies., Methods: Eighty-five cases with H. pylori infection (proved by rapid urease test and histology) were studied. In each case, the density of H. pylori colonization was graded according to the updated Sydney classification. H. pylori eradication was determined via the (14)C-Urea breath test performed 4 weeks after the end of therapy., Results: The eradication rate of H. pylori was 50% (30 out of 60) in the triple therapy and 92% (23 of 25) in the quadruple therapy group. In the triple therapy group, the eradication rate of H. pylori decreased as the initial density of H. pylori increased (density of H. pylori: 1, 58.3%; 2, 54.5%; 3, 52.4%; 4, 38.5%; 5, 33.3%). In two cases with eradication failure after quadruple therapy, the grades of bacterial density were 1 and 3., Conclusion: H. pylori density, as assessed by histological grading, may predict the usefulness of triple therapy. The higher the H. pylori density, the less effective triple therapy will be at successful eradication of H. pylori. Quadruple therapy does not seem to be negatively affected by bacterial density., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Inflammatory bowel disease (IBD) with ulcerative colitis (UC) and Crohn's disease (CD) as the most common forms is an inflammation of the gastrointestinal tract. Familial Mediterranean fever (FMF) is another inflammatory disease as well. In the current study we studied FMF gene mutations in 47 patients with IBD and 25 healthy individuals to investigate the effects of these mutations on the clinical status of IBD. Twelve mutations were analyzed by reverse hybridization after multiplex PCR amplification of DNA samples. We did not find an association between FMF gene mutations and IBD phenotypic characteristics. However, in patients without Mediterranean fever (MEFV) mutations, extraintestinal disease frequencies were higher (p<0.05). IBD has a genetic basis with multiple genes probably playing a role via several pathways during disease progression. Studying other genes interacting with FMF gene in a larger group of patients will add to the knowledge of disease pathogenesis.

Objective(s): Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with unknown etiology. The insulin resistance, immune mechanisms and oxidative stress are the main factors in its pathogenesis. Dipeptidyl peptidase IV (DPPIV) or CD26 is a protein with endocrine and immune functions. This study aimed to elicudate the changes related to DPPIV in NASH patients., Methods: Serum and urinary DPPIV activities were measured in 31 NASH patients and 17 healthy controls. The liver biopsies of 29 patients were immunolabeled for CD26., Results: The mean age of patients were 46 +/- 11 years and 14 (45%) of them were female. The serum DPPIV activity was higher in patients (57.3 +/- 7.8 U/L) than controls (43.6 +/- 10.6 U/L) (p < 0.0001), and correlated with the histopathological grade (p = 0.038, r = 0.373) and hepatosteatosis (p = 0.018, r = 0.423) but not with stage (p = 0.286), class (p = 0.286) or CD26 staining (p = 0.743). The urinary DPPIV activity was similar in patients (1.52 +/- 0.94 U/mmol creatinine) and controls (1.37 +/- 0.68 U/mmol creatinine) (p = 0.861). Three acinar zones of liver had equal CD26 expression (p = 0.076). The intensity of CD26 immunostaining was correlated with histopathological grade (p = 0.001) and hepatosteatosis (p = 0.003) but no correlation with stage or class could be detected (p = 0.610 and 0.956, respectively). In, Conclusions: The serum DPPIV activity and the staining intensity of CD26 in liver are correlated with histopathologic grade of NASH and hepatosteatosis. DPPIV can be proposed as a novel candidate with several potential functions in NASH pathogenesis.

The aim of this study was to determine the risk of polyps <6 and between 6 and 10 mm in terms of progression to malignancy and to evaluate the influence of age, gender, and colonic localization on malignancy development. Thirteen hundred sixty-nine polyps <10 mm identified in 680 patients were retrospectively evaluated. Sixty-seven and two-tenths percent of polyps <10 mm were of a neoplastic nature. The incidence of neoplasia was higher in left-sided and small polyps than diminutive polyps. In patients older than 60 years, small polyps showed a higher rate of high-risk histology than diminutive polyps,while the same relationship did not exist in other age groups. In male patients over 60 years of age, the rate of high-risk histology was higher in small polyps than in diminutive polyps.