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020. Published by Oxford University Press on behalf of ERA-EDTA.BACKGROUND Radiotherapy inadvertently affects gastrointestinal (GI) epithelial cells, causing intestinal barrier disruption and increased permeability. OBJECTIVE We examined the effect of amino acid-based oral rehydration solution (AA-ORS) on radiation-induced changes of intestinal barrier function and epithelial tight junctions (TJs) in a randomized experimental study using a total-body irradiation (TBI) mouse model. METHODS Eight-week-old male Swiss mice received a single-dose TBI (0, 1, 3, or 5 Gy), and subsequent gastric gavage with AA-ORS (threonine, valine, serine, tyrosine, and aspartic acid) or saline for 2 or 6 d. Intestinal barrier function of mouse ileum was characterized by electrophysiological analysis of conductance, anion selectivity, and paracellular permeability [fluorescein isothiocyanate (FITC)-dextran]. Ultrastructural changes of TJs were evaluated by transmission electron microscopy. Membrane protein and mRNA expression of claudin-1, -2, -3, -5, and -7, occludin, and E-cadherin were analyithin 6 d, whereas claudin-2 decreased indicating restitution of TJ proteins. CONCLUSIONS Radiation-induced functional and structural disruption of the intestinal barrier in mice is reversed by AA-ORS rendering AA-ORS a potential treatment option in prospective clinical trials in patients with gastrointestinal barrier dysfunction. Copyright © The Author(s) 2020.Hfq regulates bacterial gene expression post-transcriptionally by binding small RNAs and their target mRNAs, facilitating sRNA-mRNA annealing, typically resulting in translation inhibition and RNA turnover. Hfq is also found in the nucleoid and binds double-stranded (ds) DNA with a slight preference for A-tracts. Here, we present the crystal structure of the Escherichia coli Hfq Core bound to a 30 bp DNA, containing three 6 bp A-tracts. Although previously postulated to bind to the 'distal' face, three statistically disordered double stranded DNA molecules bind across the proximal face of the Hfq hexamer as parallel, straight rods with B-DNA like conformational properties. One DNA duplex spans the diameter of the hexamer and passes over the uridine-binding proximal-face pore, whereas the remaining DNA duplexes interact with the rims and serve as bridges between adjacent hexamers. Binding is sequence-independent with residues N13, R16, R17 and Q41 interacting exclusively with the DNA backbone. Atomic force microscopy data support the sequence-independent nature of the Hfq-DNA interaction and a role for Hfq in DNA compaction and nucleoid architecture. Our structure and nucleic acid-binding studies also provide insight into the mechanism of sequence-independent binding of Hfq to dsRNA stems, a function that is critical for proper riboregulation. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.BACKGROUND Blood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target 150 mmHg. Associations with mortality varied between non-frail less then 85 and frail 75-84-year-olds and all above 85 years. SBPs above the 130-139-mmHg reference were associated with lower mortality risk, particularly in moderate to severe frailty or above 85 years (e.g. 75-84 years 150-159 mmHg Hazard Ratio (HR) mortality compared to 130-139 non-frail HR = 0.94, 0.92-0.97; moderate/severe frailty HR = 0.84, 0.77-0.92). SBP less then 130 mmHg and Diastolic(D)BP less then 80 mmHg were consistently associated with excess mortality, independent of BP trajectory toward the end of life. CONCLUSIONS In representative primary-care patients aged ≥75, BP less then 130/80 was associated with excess mortality. Hypertension was not associated with increased mortality at ages above 85 or at ages 75-84 with moderate/severe frailty, perhaps due to complexities of co-existing morbidities. The priority given to aggressive BP reduction in frail older people requires further evaluation. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society.BACKGROUND Choline is an essential nutrient for brain growth and other processes in the developing neonate. The impact of a maternal plant-based diet on the choline composition of breast milk is unknown. OBJECTIVE We assessed the water-soluble choline content of milk from lactating women in the United States following 3 dietary patterns vegan, vegetarian, and nonvegetarian. METHODS We conducted a cross-sectional study of 74 healthy lactating women who provided a single breast-milk sample using a standardized collection protocol. TAK-875 Participants completed a food-frequency screener and were classified as follows nonvegetarians (NONVEG) consumed meat; vegetarians (VEGT) consumed milk, dairy, and/or fish; and vegans (VEGAN) consumed animal products less than monthly. Primary outcomes measured were the concentration (in milligrams per liter) and distribution (percentage) of choline from the following water-soluble forms free choline, phosphocholine (PCho), and glycerophosphocholine (GPC). Differences between diet groCopyright © The Author(s) 2019.BACKGROUND Pipeline embolization device (PED; Medtronic) and stent-assisted coiling (SAC) are established modalities for treatment of intracranial aneurysms. OBJECTIVE To comparatively assess the efficacy of these techniques. METHODS We conducted a retrospective analysis of patients with aneurysms treated at our institution with either PED from 2013 to 2017 or SAC from 2009 to 2015. All large (>10 mm), ruptured, fusiform, anterior communicating artery, posterior circulation aneurysms, and patients with no available follow-up imaging were eliminated before running the propensity score matching (PSM). Patients were matched using nearest neighbor controlling for age, gender, smoking, exact location, maximal diameter, and presence of multiple aneurysms. Total hospital costs for equipment and implants were calculated from procedure product and hospital billing records, and compared between the propensity-matched pairs. link2 RESULTS Out of 165 patients harboring 202 aneurysms; 170 (84.2%) were treated with the PED, and 32 (15.8%) were treated using SAC. PSM resulted in 23 matched pairs; with significantly longer follow up in the SAC group (mean 29.8 vs 14.1 mo; P = .0002). Complete occlusion rates were not different (82.6 vs 87%; P = .68), with no difference between the groups for modified Rankin Scale on last clinical follow-up, procedural complications or retreatment rates. Average total costs calculated from the hospital records, including equipment and implants, were not different between propensity-score matched pairs (P = .48). CONCLUSION PED placement and SAC offer equally efficacious occlusion rates, functional outcomes, procedural complication rates, and cost profiles for small unruptured anterior circulation saccular aneurysms which do not involve the anterior communicating artery. Copyright © 2020 by the Congress of Neurological Surgeons.BACKGROUND Pineal region tumors are associated with the ventricular system. Endoscopic third ventriculostomy (ETV) is often performed at the same time as tumor biopsy. OBJECTIVE To investigate the volume of brain possibly undergoing injury and forniceal stretching during ETV and tumor biopsy. METHODS We performed a retrospective review of preoperative magnetic resonance imagings (MRIs) and computed tomography (CTs) of patients with pineal region masses and used volumetric image-guided navigation to simulate a 1-burr-hole vs a 2-burr-hole approach through the brain parenchyma. We compared the volumes of parenchyma and fornix at the risk of injury. RESULTS The ideal entry point for ETV using 2 burr holes was a mean ± standard deviation (SD) of 25.8 ± 6 mm from the midline and 11.4 ± 9 mm behind the coronal suture. The ideal entry point using 2 burr holes for tumor biopsy was 25.7 ± 8 mm from the midline and 53.7 ± 14 mm anterior to the coronal suture. link3 With 1 burr hole, the mean ± SD volume of brain parenchyma at risk was 852 ± 440 mm3. The volume of brain parenchyma at risk with 2 burr holes was 2159 ± 474 mm3 (P less then .001; paired t-test). The use of 1 burr hole predisposed the fornix to 14 ± 3 mm of possible stretch, which was minimized with the 2-burr-hole approach. CONCLUSION Using 1 burr hole for both the ETV and tumor biopsy is less likely to traumatize the brain parenchyma than using 2 burr holes. However, 1 burr hole predisposes the fornix to stretch injury. We recommend tailoring the entry to each patient according to their anatomy rather than using a 1-size-fits-all approach. Copyright © 2020 by the Congress of Neurological Surgeons.Investigating potential gray matter differences in adolescents presenting higher levels of schizotypy personality traits could bring further insights into the development of schizophrenia spectrum disorders. Research has yet to examine the morphological correlates of schizotypy features during adolescence prospectively, and no information is available on the developmental trajectories from adolescence to adulthood. We employed mixed model regression analysis to investigate developmental trajectories of cortical thickness (CT) in relation to schizotypy dimensions in a cohort of 109 adolescents from the general population for whom MRI-scans were acquired over a 5-year period, culminating in a total of 271 scans. Structural data were processed with FreeSurfer software, statistical analyses were conducted using mixed regression models following a ROI-based approach, and schizotypy was assessed with the Schizotypal Personality Questionnaire (SPQ). Accelerated thinning was observed in the posterior cingulate [email protected] Although clinical trials testing immunotherapies in glioblastoma (GBM) have yielded mixed results, new strategies targeting tumor-specific somatic coding mutations, termed neoantigens, represent promising therapeutic approaches. We characterized the microenvironment and neoantigen landscape of the aggressive CT2A GBM model in order to develop a platform to test combination checkpoint blockade and neoantigen vaccination. METHODS Flow cytometric analysis was performed on intracranial CT2A and GL261 tumor-infiltrating lymphocytes (TIL). Whole exome DNA and RNA sequencing of the CT2A murine GBM was employed to identify expressed, somatic mutations. Predicted neoantigens were identified using the pVAC-seq software suite and top-ranking candidates were screened for reactivity by IFN-gamma enzyme linked immunospot (ELISPOT) assays. Survival analysis was performed comparing neoantigen vaccination, αPD-L1, or combination therapy. RESULTS Compared to the GL261 model, CT2A exhibited immunologic features consir Neuro-Oncology. All rights reserved. For permissions, please e-mail [email protected] you are a gazelle bounding to the richest tract of grassland or a return customer heading to the freshest farm stand at a crowded market, the ability to learn the value of spatial locations is important in adaptive behavior. The ventromedial frontal lobe (VMF) is implicated in value-based decisions between objects and in flexibly learning to choose between objects based on feedback. However, it is unclear if this region plays a material-general role in reward learning. Here, we tested whether VMF is necessary for learning the value of spatial locations. People with VMF damage were compared with healthy participants and a control group with frontal damage sparing VMF in an incentivized spatial search task. Participants chose among spatial targets distributed among distractors, rewarded with an expected value that varied along the right-left axis of the screen. People with VMF damage showed a weaker tendency to reap reward in contralesional hemispace. In some individuals, this impairment could be dissociated from the ability to make value-based decisions between objects, assessed separately.
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