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The effects of phenytoin (PHT), levetiracetam (LEV) or their adjunctive treatment on the hypothalamic-pituitary-testicular axis in male Wistar rats were determined. Twenty-eight male rats (150-180 g) were randomised into four groups (N = 7). Groups I to IV received intraperitoneal treatment of either normal saline (0.2 ml i.p) or PHT (50 mg/kg i.p) or LEV (50 mg/kg) or PHT (25 mg/kg) and LEV (25 mg/kg) combination for 28 days. The organ weight, concentrations of reproductive hormones and semen profile were determined, while the brain, epididymis and testis were preserved in 10% neutral-buffered formalin for the histomorphological study. Data were analysed using descriptive and inferential statistics. The results were presented as mean ± SEM in graphs or tables, while the level of significance was taken at p less then .05. The semen profile was altered significantly in all the treatment groups. The gonadotrophic releasing hormone, luteinising hormone and testosterone concentration decreased significantly in the PHT- and PHT + LEV-treated groups compared with control. There were various disruptions in the hypothalamus, pituitary and testis of the PHT- and PHT + LEV adjunctive-treated rats. In conclusion, chronic PHT + LEV treatment may pose deleterious effects on the hypothalamic-pituitary-testicular axis than single treatment of either of the two drugs in male rats.The ε4 allele of the gene Apolipoprotein E is the major genetic risk factor for Alzheimer's Disease. APOE ε4 has been associated with changes in brain structure in cognitively impaired and unimpaired subjects, including atrophy of the hippocampus, which is one of the brain structures that is early affected by AD. In this work we analyzed the impact of APOE ε4 gene dose and its association with age, on hippocampal shape assessed with multivariate surface analysis, in a ε4-enriched cohort of n = 479 cognitively healthy individuals. Furthermore, we sought to replicate our findings on an independent dataset of n = 969 individuals covering the entire AD spectrum. We segmented the hippocampus of the subjects with a multi-atlas-based approach, obtaining high-dimensional meshes that can be analyzed in a multivariate way. We analyzed the effects of different factors including APOE, sex, and age (in both cohorts) as well as clinical diagnosis on the local 3D hippocampal surface changes. We found specific regions on the hippocampal surface where the effect is modulated by significant APOE ε4 linear and quadratic interactions with age. We compared between APOE and diagnosis effects from both cohorts, finding similarities between APOE ε4 and AD effects on specific regions, and suggesting that age may modulate the effect of APOE ε4 and AD in a similar way.This research investigated whether biases in processing threatening emotional cues operate as an indirect pathway through which parental harsh discipline is associated with adolescent socio-emotional functioning. Participants were 192 adolescents (M age = 12.4), and their parents assessed over two years. Findings revealed two significant indirect pathways involving fear processing. Greater parental harsh discipline was linked to more emotional response inhibition difficulty for fear, which was linked to more depressive symptoms in the following year. Greater parental harsh discipline was also associated with more emotional response inhibition difficulty for fear, and thereby, more peer problems later. Findings suggest that adolescent emotional processing operated as an indirect pathway linking parental harsh discipline and adolescent socio-emotional functioning within the broader social context.
The multi-exponential T
decay of the MRI signal from cerebral white matter can be separated into short T
components related to myelin water and long T
components related to intracellular and extracellular water. In this study, we investigated to what degree the apparent myelin water fraction (MWF) depends on the angle between white matter fibers and the main magnetic field.
Maps of the apparent MWF were acquired using multi-echo Carr-Purcell-Meiboom-Gill and gradient-echo spin-echo sequences. The Carr-Purcell-Meiboom-Gill sequence was acquired with a TR of 1073 ms, 1500 ms, and 2000 ms. The fiber orientation was mapped with DTI. By angle-wise pooling the voxels across the brain's white matter, orientation-dependent apparent MWF curves were generated.
We found that the apparent MWF varied between 25% and 35% across different fiber orientations. Furthermore, the selection of the TR influences the apparent MWF.
White matter fiber orientation induces a strong systematic bias on the estimation of the apparent MWF. This finding has implications for future research and the interpretation of MWI results in previously published studies.
White matter fiber orientation induces a strong systematic bias on the estimation of the apparent MWF. This finding has implications for future research and the interpretation of MWI results in previously published studies.Post-synthetic modification (PSM) is a prevalent and powerful strategy to introduce desired functionalities into covalent organic frameworks (COFs) for functional products, expediting their applications vastly. Herein, we demonstrate a PSM strategy for functionalizing brominated COFs via the well-developed Suzuki-Miyaura cross-coupling. By this, a variety of functionalities were installed into COFs efficiently, while the crystallinity and porosity of COFs was well-retained. As a proof-of-concept, BrCOF-2 was modified with trifluoromethyl groups to produce a SF6 adsorbent with remarkably enhanced properties. This facile and versatile approach opens a new door for the synthesis of functional COFs, and greatly expands the scope of their structural design aiming for various properties and applications.Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening microangiopathic hemolytic anemia characterized by thrombocytopenia, hemolytic anemia, and ischemic organ damage. It is mainly caused by an autoreactive antibody directed at ADAMTS13. Immunotherapy is frequently associated with autoimmune complications in patients with cancer, but only three cases of TTP have been reported, none implicating single treatment with the anti-programmed cell death receptor 1 ligand antibody nivolumab. We present the first identified and reported case of nivolumab-associated TTP in a 51-year-old woman with stage IIIc anal carcinoma who achieved complete response following chemoradiation and received adjuvant nivolumab as part of a randomized clinical trial. Twelve weeks into treatment, she presented with dark urine, progressive fatigue, and headache. TTP diagnosis was based on laboratory evidence of hemolytic anemia, thrombocytopenia, and ADAMTS13 activity of 9% associated with an inhibitor. A2ti-2 ic50 She was treated with daily plasma exchange and oral prednisone and responded well to treatment, with platelet counts over 100 K/cmm within 4 days.
Homepage: https://www.selleckchem.com/products/a2ti-2.html
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