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Neurons typically generate action potentials at their axon initial segment based on the integration of synaptic inputs. In many neurons, the axon extends from the soma, equally weighting dendritic inputs. A notable exception is found in a subset of hippocampal pyramidal cells where the axon emerges from a basal dendrite. This structure allows these axon-carrying dendrites (AcDs) a privileged input route. We found that in male mice, such cells in the CA1 region receive stronger excitatory input from the contralateral CA3, compared with those with somatic axon origins. This is supported by a higher count of putative synapses from contralateral CA3 on the AcD. These findings, combined with prior observations of their distinct role in sharp-wave ripple firing, suggest a key role of this neuron subset in coordinating bi-hemispheric hippocampal activity during memory-centric oscillations. [ABSTRACT FROM AUTHOR]

Abstract Sclerosing cholangitis in critically ill patients (SC-CIP) is a progressive cholestatic disease of unknown aetiology characterized by chronic biliary infections. Hence we hypothesized that common NOD2 (nucleotide-binding oligomerisation domain containing 2) gene variants, known risk factors for Crohn’s disease and bacterial translocation in liver cirrhosis, increase the odds of developing SC-CIP. Screening of 4,641 endoscopic retrograde cholangiography procedures identified 17 patients with SC-CIP, who were then genotyped for the three common NOD2 mutations (Cohort 1, discovery cohort). To validate the association, we subsequently tested these NOD2 variants in 29 patients from SC-CIP cohorts of three additional medical centers (Cohort 2, replication cohort). In Cohort 1, the NOD2 variants were present in 5 of 17 SC-CIP patients (29.4%), which is twice the frequency of the general population. These results were replicated in Cohort 2 with 8 patients (27.6%) showing NOD2 mutations. In contrast, polymorphisms of hepatocanalicular transporter genes did not have major impact on SC-CIP risk. This first study on genetic susceptibility in SC-CIP patients shows an extraordinary high frequency of NOD2 variation, pointing to a critical role of inherited impaired anti-bacterial defense in the development of this devastating biliary disease.

Background and Study Aims. Patients undergoing therapeutic endoscopic retrograde cholangiography (ERC) may require different amounts of sedative agents depending on demographic characteristics, indication of ERC, and/or endoscopic intervention. Patients and Methods. We retrospectively analyzed all patients undergoing therapeutic ERC from 2008 – 2014 who received deep sedation with propofol ± midazolam. Results. A total of 2448 ERC procedures were performed in 781 patients. The cumulative per procedure propofol dose in the different groups was as follows: PSC 479 mg (±256), bile duct stones 356 mg (±187), benign stenosis/cholestasis 395 mg (±228), malignant stenosis 401 mg (±283), and postliver transplant complications 391 mg (±223) (p < 0.05). Multivariable analysis showed that dilatation therapy (p = 0.001), age (p = 0.001), duration of the intervention (p = 0.001), BMI (p = 0.001), gender (p = 0.001), platelet count (p = 0.003), and bilirubin (p = 0.043) influence independently the propofol consumption. Conclusions. Demographic characteristics and endoscopic interventions have a distinct influence on the amount of sedation required for therapeutic ERC. Although the sedation-associated complication rate is low optimization of sedative regimens is a prime goal to further reduce adverse events of therapeutic ERC.

Background and study aims Patients with primary sclerosing cholangitis (PSC) require repeated endoscopic retrograde cholangiography (ERC). Our aim was to evaluate whether patients with PSC require higher doses of sedation during ERC. Patients and methods We retrospectively analyzed all patients undergoing ERC from 2006 to 2013 who received conscious sedation with propofol and midazolam. The duration of the intervention and a potential progression of propofol consumption or intervention time by visit number were analyzed. Univariable and multivariable analyses were performed to identify independent factors which influence propofol consumption. Results A total of 2962 ERC procedures were performed in 1211 patients. Patients with PSC (n = 157) underwent 461 ERC procedures whereas patients without PSC (n = 1054) had 2501 ERC examinations. The total median propofol dose was 450 mg (290 – 630 mg) for patients with PSC and 300 mg (200 – 450 mg) for the non-PSC group (P