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Although anatomical, lesion, and imaging studies of the hippocampus indicate qualitatively different information processing along its septo-temporal axis, physiological mechanisms supporting such distinction are missing. We found ...
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Although anatomical, lesion, and imaging studies of the hippocampus indicate qualitatively different information processing along its septo-temporal axis, physiological mechanisms supporting such distinction are missing. We found fundamental differences between the dorsal (dCA3) and the ventral-most parts (vCA3) of the hippocampus in both environmental representation and temporal dynamics. Discrete place fields of dCA3 neurons evenly covered all parts of the testing environments. In contrast, vCA3 neurons (1) rarely showed continuous two-dimensional place fields, (2) differentiated open and closed arms of a radial maze, and (3) discharged similar firing patterns with respect to the goals, both on multiple arms of a radial maze and during opposite journeys in a zigzag maze. In addition, theta power and the fraction of theta-rhythmic neurons were substantially reduced in the ventral compared with dorsal hippocampus. We hypothesize that the spatial representation in the septo-temporal axis of the hippocampus is progressively decreased. This change is paralleled with a reduction of theta rhythm and an increased representation of nonspatial information.
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The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). Here, we report that tumor 2HG is elevated in a high percentage of patients with cyto...
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The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). Here, we report that tumor 2HG is elevated in a high percentage of patients with cytogenetically normal acute myeloid leukemia (AML). Surprisingly, less than half of cases with elevated 2HG possessed IDH1 mutations. The remaining cases with elevated 2HG had mutations in IDH2, the mitochondrial homolog of IDH1. These data demonstrate that a shared feature of all cancer-associated IDH mutations is production of the oncometabolite 2HG. Furthermore, AML patients with IDH mutations display a significantly reduced number of other well characterized AML-associated mutations and/or associated chromosomal abnormalities, potentially implicating IDH mutation in a distinct mechanism of AML pathogenesis.
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Atrial fibrillation (AF) remains the most common clinically encountered arrhythmia. Unlike supraventricular arrhythmias that use a defined mechanism, AF involves a wide spectrum of arrhythmias from lone AF to paroxysmal to chronic...
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Atrial fibrillation (AF) remains the most common clinically encountered arrhythmia. Unlike supraventricular arrhythmias that use a defined mechanism, AF involves a wide spectrum of arrhythmias from lone AF to paroxysmal to chronic AF. AF is an arrhythmia that may develop in several ways. Mechanical remodeling manifests as decreased atrial contractility and increased atrial compliance which leads to a stretch of the atrial myocardium. Atrial remodeling may also increase in atrial fibrosis which can slow conduction velocity and can shorten the refractory period in atria with long-standing AF. It is still unclear whether initiation of AF activates direct inflammatory effects or whether the presence of a pre-existing systemic inflammatory state promotes further persistence of AF. Currently, the patient population undergoing AF ablation has greatly expanded. Patients are older and have larger left atrial size and are more likely to have persistent/permanent AF. It is likely that AF comprises a spectrum of disease with no single mechanism adequate enough to comprehensively explain AF and its variability. The management of patients with AF involves elements of anticoagulation, rate control and rhythm control and such treatment strategies are not necessarily mutually exclusive of each other.
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OBJECTIVE: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studi...
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OBJECTIVE: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. METHODS: We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). RESULTS: Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. CONCLUSIONS: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.
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Fat infiltration and inflammation cause liver injury and fibrosis and may progress to nonalcoholic steatohepatitis (NASH) and end-stage liver disease. Currently, there are no effective treatments for NASH. Zeaxanthin is a caroteno...
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Fat infiltration and inflammation cause liver injury and fibrosis and may progress to nonalcoholic steatohepatitis (NASH) and end-stage liver disease. Currently, there are no effective treatments for NASH. Zeaxanthin is a carotenoid which has been shown to be preferentially accumulated in the adipose tissue and liver. We hypothesized that treatment with zeaxanthin may decrease oxidative stress in the liver and, possibly, halt the inflammation and fibrosis associated with NASH. Here we tested zeaxanthin effects in preventing progression of liver injury in a model of NASH. Mongolian gerbils, fed a methionine-choline-deficient diet, were treated with different doses of zeaxanthin. We assessed histopathological changes by hematoxylin-eosin and Masson trichrome staining and determined oxidative stress by measuring lipid peroxidation. The obtained results show that zeaxanthin significantly prevented NASH progression by decreasing oxidative stress and liver fibrosis, thus suggesting a potential therapeutic application for this carotenoid in the management of NASH.
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BACKGROUND: In children with extrahepatic portal vein obstruction (EHPVO), formation of a mesentericoportal bypass (Rex shunt) restores hepatopetal flow, relieves portal hypertension, and reduces variceal bleeding and hypersplenis...
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BACKGROUND: In children with extrahepatic portal vein obstruction (EHPVO), formation of a mesentericoportal bypass (Rex shunt) restores hepatopetal flow, relieves portal hypertension, and reduces variceal bleeding and hypersplenism. The Rex shunt is created by inserting a vein graft between the superior mesenteric vein and the umbilical segment (Rex) of the left portal vein within the Rex recess of the liver. The preoperative evaluation of a patient with EHPVO includes an accurate assessment of the venous inflow and outflow. The inflow portal vein is readily assessed by ultrasound and magnetic resonance imaging. The outflow intrahepatic portal vein is harder to assess. We report our experience of patients evaluated with wedged hepatic vein carbon dioxide portography (WHVCP). METHOD: All children referred for venography from October 2001 to October 2007 were prospectively identified, and clinical and radiologic data were reviewed retrospectively. The imaging findings were correlated to findings at surgery. RESULTS: Eleven children (range, 3-14 years, median, 6 years) were referred for preoperative wedged hepatic venography. The left portal vein at the Rex recess was clearly identified in 9 patients (82%). In the other 2 patients (18%), the Rex segment was not identified despite opacification of left and right intrahepatic portal veins; this was taken to indicate an occluded segment. Wedged venography was performed with carbon dioxide in 10 patients (91%). Carbon dioxide was contraindicated in the final patient because of the presence of a ventricular septal defect. CONCLUSION: Our series demonstrates the use of WHVCP as a diagnostic tool in preoperative assessment of the Rex segment of left portal vein in children with extrahepatic portal vein obstruction.
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AIM OF THE STUDY: Zanthoxylum armatum DC is described as a hepatoprotective in Ayurveda, the Indian system of medicine. However, there is no scientific basis or reports in the modern literature regarding its usefulness as a hepato...
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AIM OF THE STUDY: Zanthoxylum armatum DC is described as a hepatoprotective in Ayurveda, the Indian system of medicine. However, there is no scientific basis or reports in the modern literature regarding its usefulness as a hepatoprotective agent. The present study was carried out to evaluate the hepatoprotective activity of ethanolic extract of bark of Zanthoxylum armatum DC in CCl(4) induced hepatotoxicity in male Wistar rats. MATERIALS AND METHODS: Ethanolic extracts at doses of 100, 200, and 400mg/kg were administered orally once daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum bilirubin, total protein and serum antioxidant enzymes along with histopathological studies of liver tissue. RESULTS: The substantially elevated serum enzymatic levels of serum transaminases, alkaline phosphatase and total bilirubin were significantly restored towards normalization by the extracts. Bark extracts significantly increased the levels of antioxidant enzymes: superoxide dismutase, catalase and glutathione. Phytochemical analysis revealed presence of isoquinoline alkaloid, berberine, as well as flavonoids and phenolic compounds, which have been known for their hepatoprotective activities. CONCLUSIONS: Zanthoxylum armatum DC possesses significant protective effect against hepatotoxicity induced by CCl(4) which may be attributed to the individual or combined action of phytoconstituents present in it.
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BACKGROUND AND AIMS:We have previously reported that the throm-bolytic tenecteplase (TNK) is able to penetrate the retina following an intravitreal injection of 50mug with no evidence of retinal toxicity. The purpose of this repor...
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BACKGROUND AND AIMS:We have previously reported that the throm-bolytic tenecteplase (TNK) is able to penetrate the retina following an intravitreal injection of 50mug with no evidence of retinal toxicity. The purpose of this report, which is the first in humans, is to assess its efficacy and safety in the management of patients with submacular haemorrhage (SMH) secondary to age-related macular degeneration.
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