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Cognitive deficits and brain myoInositol are early biomarkers of epileptogenesis in a rat model of epilepsy, Neurobiology of Disease (2016Disease ( ), doi: 10.1016Disease ( /j.nbd.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E DM A N U S C R I P T ACCEPTED MANUSCRIPT AbstractOne major unmet clinical need in epilepsy is the identification of therapies to prevent or arrest epilepsy development in patients exposed to a potential epileptogenic insult. The development of such treatments has been hampered by the lack of non-invasive biomarkers that could be used to identify the patients at-risk, thereby allowing to design affordable clinical studies. Our goal was to test the predictive value of cognitive deficits and brain astrocyte activation for the development of epilepsy following a potential epileptogenic injury. We used a model of epilepsy induced by pilocarpine-evoked status epilepticus (SE) in 21-day old rats where 60-70% of animals develop spontaneous seizures after around 70 days, although SE is similar in all rats. Learning was evaluated in the Morris water-maze at days 15 and 65 post-SE, each time followed by proton magnetic resonance spectroscopy for measuring hippocampal myo-Inositol levels, a marker of astrocyte activation. Rats were video-EEG monitored for two weeks at seven months post-SE to detect spontaneous seizures, then brain histology was done. Behavioral and imaging data were retrospectively analysed in epileptic rats and compared with non epileptic and control animals. Rats displayed spatial learning deficits within three weeks from SE. However, only epilepsy-prone rats showed accelerated forgetting and reduced learning rate compared to both rats not developing epilepsy and controls. These deficits were associated with reduced hippocampal neurogenesis. myoInositol levels increased transiently in the hippocampus of SE-rats not developing epilepsy while this increase persisted until spontaneous seizures onset in epilepsy-prone rats, being associated with a local increase in S100-positive astrocytes. Neuronal cell loss was similar in all SE-rats. Our data show that behavioral deficits, together with a non-invasive marker of astrocyte activation, predict which rats develop epilepsy after an acute injury. These measures have potential clinical relevance for identifying individuals at-risk for developing epilepsy following exposure to epileptogenic insults, and consequently, for designing adequately powered antiepileptogenesis trials.

BackgroundA meta-analysis and six randomized controlled trials show higher 30-day complication rates with laparoscopic Roux-en-Y gastric bypass (LRYGB) than with laparoscopic sleeve gastrectomy (LSG).AimTo identify any difference in 30-day outcomes of patients treated with LRYGB or LSG when a standardized technique and identical post-operative protocol was followed with all procedures being conducted either by or under the supervision of a single consultant surgeon who had significant experience in bariatric surgery prior to commencing independent practice.MethodsA prospectively collected database of all patients under primary LRYGB or LSG, between March 2010 and February 2017, was analyzed. Data on demographics, length-of-stay (LOS), conversion to open, 30-day complications and mortality were reviewed.ResultsOver a seven-year period, 485 patients (LRYGB-279 and LSG-206) were included. There were no significant demographic differences and no difference in the pre-operative risk scoring [American Society of Anesthesiologists (ASA) and obesity surgery mortality risk score (OSMRS)] between the groups. There was no significant difference between the groups in terms of LOS (p = 0.275), complications (p = 0.920), re-admissions (p = 0.593) or re-operations (p = 0.366) within 30-days. There were no conversions to open or in-patient mortality in either group.ConclusionsUnlike previous studies, we found no difference in early complication rates between LRYGB and LSG in a comparable cohort when performed by a surgeon with sufficient experience in bariatric surgery.

Introduction Laparoscopic Roux-en-Y gastric bypass (LRYGB) is technically demanding and has an associated learning curve. We published previously that bariatric fellowship reduces the learning curve of primary LRYGB and improves patient outcomes after one year of independent practice. However, the long-term effect of fellowship is unknown. We therefore aimed to compare the 30-day outcomes of LRYGB between the first year of a surgeon's independent practice with the subsequent six years. Materials and methods A prospective database of patients undergoing primary LRYGB under a single surgeon from March 2010 until February 2017 was analysed. Two groups were studied: first year (< 1 year) and the subsequent six years (≥ 1 year) of independent practice. Patient demographics, length of hospital stay, conversion to open surgery, perioperative complications and mortality were compared. Results Among 279 eligible patients, 74 (26.5%) were in the < 1 year group and 205 (73.5%) in ≥ 1 year group. The preoperative risk scores, American Society of Anesthesiologists (ASA) grade, P = 0.00; obesity surgery mortality risk score (OS-MRS), P = 0.04) were significantly higher in ≥ 1 year group. There was no significant difference in perioperative outcomes (length of stay, P = 0.38; total complications, P = 0.20; readmissions, P = 1.00; reoperations, P = 0.60) between the two groups. Conclusions Bariatric fellowship reduces the learning curve for LRYGB and helps to achieve excellent outcomes in the first and subsequent years of independent practice. The higher risk profile of ≥ 1 year group did not equate to an increase in complications, suggesting that experience and standardisation may help in handling complex cases. To our knowledge, this represents the only such study in the literature.

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