Ryemcneil1609

BACKGROUND Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is the most frequent fatty acid oxidation (FAO) defect in humans. MCAD-deficient fibroblasts are more resistant to oxidative stress-induced cell death than other FAO defects and healthy controls. METHODS Herein we investigate the antioxidant response and mitochondrial function in fibroblasts from MCAD-deficient patients (c.985 A>G/c.985 A>G) and healthy controls. RESULTS MCAD-deficient fibroblasts showed increased level of mitochondrial superoxide, while lipids were less oxidatively damaged, and higher amount of manganese superoxide dismutase were detected compared to healthy controls, showing forceful antioxidant system in MCADD. We showed increased maximal respiration and reserve capacity in MCAD-deficient fibroblasts compared to controls, indicating more capacity through the tricarboxylic acid (TCA) cycle and subsequently respiratory chain. This led us to study the pyruvate dehydrogenase complex (PDC), the key enzyme in the glycolysis releasing acetyl-CoA to the TCA cycle. MCAD-deficient fibroblasts displayed not only significantly increased PDC but also increased lipoylated PDC protein levels compared to healthy controls. CONCLUSIONS Based on these findings, we raise the interesting hypothesis that increased PDC-bound lipoic acid, synthesized from accumulated octanoic acid in MCADD, may affect the cellular antioxidant pool in MCADD.Bernhard von Gudden was the founder of the famous school of psychiatry and neuroanatomy in Munich, Germany. Beyond his association with the mysterious death of King Ludwig II of Bavaria, not much is known about Bernhard von Gudden's work in neuroanatomy. He pioneered fiber tract mapping by studying the effects of neurodegeneration following brain lesions. His ideas and work lay the foundation for subsequent fiber tract mapping strategies including the latest method using diffusion tensor magnetic resonance. This paper describes and acknowledges his contribution to the field, now collectively known as connectomics, and describes how it has become an essential tool in modern stereotactic neurosurgery. © 2020 S. Karger AG, Basel.BACKGROUND Symptoms caused by chronic pancreatitis (CP) are common but often elusive hampering therapeutic decisions. Though correlations of morphologic findings in imaging and clinical appearance remain vague. We aimed in investigating whether a distinct combination of clinical parameters can better define the extent of pancreatic insufficiency and disease burden. METHODS Data from 350 CP patients were evaluated retrospectively from a single center data base following predefined criteria (i) confirmed CP, (ii) endoscopic ultrasound (EUS) plus (iii) fecal elastase-1 testing, (iv) age ≥18 years, and (v) Cambridge Score ≥1 on EUS evaluation. RESULTS In total, 182 patients (137 male, 45 female) fulfilled criteria. Median age was 52 years (range 19-88 years). Etiology distributed as follows idiopathic 50%, alcohol 42.3%, autoimmune 7.7%. https://www.selleckchem.com/products/dup-697.html Totally, 56.6% of patients suffered from chronic pain that was significantly associated with male sex and younger age. Stool elastase-1 activity discriminated exocrine pancreatic function in Cambridge IV significantly better than in lower stages. Similarly, the endocrine function was significantly more reduced in Cambridge IV CP. Multinominal regression analysis revealed (i) presence of diabetes, (ii) presence of complications, and (iii) extent of Cambridge score as main determinants for exocrine impairment. CONCLUSION A high disease burden is linked to extensive morphological alterations in EUS, while pain is more frequent in younger and male patients. The etiology of CP predicts the course of disease in terms of complications. © 2020 S. Karger AG, Basel.BACKGROUND The characteristics of Helicobacter pylori (HP) infection-negative gastric cancer (HPINGC) have not been well documented because of the rareness. The aim of this study was to classify HPINGC endoscopically and clinicopathologically. METHODS This retrospective study included 1,741 early gastric cancer lesions and evaluated their HP infection status. Expression levels of MUC5AC, MUC6, MUC2, CD10, p53, MIB-1, pepsinogen-I, H+/K+ ATPase, chromogranin A, E-cadherin, and gastrin were evaluated in tumors by immunohistochemistry (IHC). RESULTS Among the analyzed lesions, 19 (1.1%) were diagnosed as HPINGC and classified into 6 types undifferentiated (5 lesions), fundic gland (2 lesions), cardiac gland (1 lesion), pyloric gland (3 lesions), foveolar (5 lesions), and mixed (3 lesions) types. Undifferentiated lesions were of pale color, with unclear demarcation and decreased E-cadherin expression. Fundic-type lesions were tan to reddish in color, with submucosal tumor-like protrusions, and positive for pepsinogen-I and H+/K+ ATPase. The cardiac gland type was located in the gastroesophageal junction and was positive for MUC6 and pepsinogen-I. Pyloric gland-type lesions were of the same color as normal mucosa, with mild elevation and unclear demarcation, likely positive for CD10 and chromogranin A. Foveolar epithelial-type lesions were white and elevated, with defined demarcation, and contained MUC5AC-positive cells. Mixed-type lesions, showing various staining patterns in IHC, had both elevated and depressed shape and reddish color. CONCLUSION Endoscopic observation and IHC were useful for classifying the characteristics of HPINGC, which may preserve the characteristics of its region of origin. © 2020 S. Karger AG, Basel.BACKGROUND Our goal was to investigate the 3-year persistence rates with second-line vedolizumab and tumor necrosis factor-α (TNF-α) inhibitors (i.e., adalimumab, golimumab, infliximab) in patients with inflammatory bowel disease (IBD) who were followed in gastroenterology practices in Germany. METHODS This study included patients aged ≥18 years who had received prescriptions for second-line biological drugs in Germany between 2014 and 2017 (n = 5,150) retrieved from the longitudinal prescription database. Vedolizumab users were matched to adalimumab, golimumab, and infliximab users based on age, sex, and index year. The primary outcome of the study was the rate of persistence with vedolizumab compared with the rate of persistence with adalimumab, golimumab, and infliximab within 3 years of second-line therapy initiation in IBD patients. Persistence was estimated as therapy time without discontinuation, with discontinuation being defined as at least 90 days without any prescription for the biological drug of interest.