Descending projections from the basal forebrain to the orexin neurons in mice

The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake‐promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and γ‐aminobutyric acid (GABA)ergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata). Given the neurochemical and anatomical heterogeneity of the BF, we mapped the pattern of BF projections to the orexin neurons across multiple BF regions and neuronal types. We performed conditional anterograde tracing using mice that express Cre recombinase only in neurons producing acetylcholine, glutamate, or GABA. We found that the orexin neurons are heavily apposed by axon terminals of glutamatergic and GABAergic neurons of the substantia innominata (SI) and magnocellular preoptic area, but there was no innervation by the cholinergic neurons. Channelrhodopsin‐assisted circuit mapping (CRACM) demonstrated that glutamatergic SI neurons frequently form functional synapses with the orexin neurons, but, surprisingly, functional synapses from SI GABAergic neurons were rare. Considering their strong reciprocal connections, BF and orexin neurons likely work in concert to promote arousal, motivation, and other behaviors. J. Comp. Neurol. 525:1668–1684, 2017. © 2016 Wiley Periodicals, Inc.     

Prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations

Background

The postoperative complication is one of an indicator of poor prognosis in patients with several gastroenterological cancers after curative operations. We, herein, examined prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations.

Methods

We retrospectively analyzed 60 patients with intrahepatic cholangiocarcinoma who underwent primary curative operations from June 2002 to February 2016. Prognostic impacts of postoperative complications were analyzed using log-rank test and Cox proportional hazard model.

Results

Postoperative complications (Clavien-Dindo classification grade 3 or more) occurred in 13 patients (21.7%). Overall survival of patients without postoperative complications was significantly better than that of patients with postoperative complications (p = 0.025). Postoperative complications are independent prognostic factor of overall survival (hazard ratio 3.02; p = 0.030). In addition, bile duct resection and reconstruction (Odds ratio 59.1; p = 0.002) and hepatitis C virus antibody positive (Odds ratio 7.14; p= 0.022), and lymph node dissection (Odds ratio 6.28; p = 0.040) were independent predictors of postoperative complications.

Conclusion

Postoperative complications may be an independent predictor of poorer survival in patients with intrahepatic cholangiocarcinoma after curative operations. Lymph node dissection and bile duct resection and reconstruction were risk factors for postoperative complications, therefore we should pay attentions to perform lymph node dissections, bile duct resection and reconstruction in patients with intrahepatic cholangiocarcinoma.

     

A Prospective Multicenter Randomized Controlled Study on Interleukin‐6 Removal and Induction by a new Hemodialyzer With Improved Biocompatibility in Hemodialysis Patients: A Pilot Study

We compared interleukin‐6 (IL‐6) removal and induction between conventional polysulfone (Con) and TORAYLIGHT NV (NV) dialyzers in hemodialysis patients. Twenty patients on Con with high IL‐6 concentrations (2.7–8.5 pg/mL) were randomized to Con or NV group. Dialyzer performance was determined in NV group while patients were on Con and after being switched onto NV. Erythropoiesis‐stimulating agent (ESA) response index (ERI) was assessed every 4 months for one year. IL‐6 clearance was comparable between Con and NV. IL‐6 removal rates were comparable for the first 1 h, but were higher with NV for the entire session (P = 0.03). Before‐to‐during‐dialysis IL‐6 concentration ratios were lower with NV on the venous side after the session (P = 0.03). During the one‐year study, hemoglobin was lower in Con group than in NV group at month 8 (P = 0.046). ERI decreased in NV and increased in Con group, with a significant difference between the groups (P = 0.002). NV and Con are comparable in removing IL‐6 and both induce IL‐6. However, the data suggest that NV induces less IL‐6, which may reduce the risk of ESA hyporesponsiveness.     

PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis

Immunotherapy using anti‐PD‐1/PD‐L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD‐L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD‐L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)‐α upregulated PD‐L1 expression in PDAC cells through NF‐κB signaling. The induction of PD‐L1 expression was also caused by co‐culture with activated macrophages, and the upregulation was inhibited by neutralization with anti‐TNF‐α antibody after co‐culture with activated macrophages. PD‐L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD‐L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8‐positive T‐cell infiltration. These findings indicate that tumor‐infiltrating macrophage‐derived TNF‐α could be a potential therapeutic target for PDAC.     

Three-dimensional Evaluation of Mandibular Volume in Patients with Cleft Lip and Palate During the Deciduous Dentition Period

ObjectivesTo examine the relationship between mandibular volume and craniofacial morphology in patients with cleft lip and palate using cone beam computed tomography (CBCT) and to compare these findings with control (noncleft) patients undergoing CBCT for other purposes during the deciduous dentition period.Materials and MethodsEighty-four patients were categorized into the unilateral cleft lip and alveolus (UCLA) group (n = 25; mean age, 4.60 ± 0.40 years), unilateral cleft lip and palate (UCLP) group (n = 23; mean age, 4.52 ± 0.39 years), bilateral cleft lip and palate (BCLP) group (n = 22; mean age, 4.54 ± 0.37 years), and control group without cleft (n = 14; mean age, 5.19 ± 0.52 years). Mandibular volume and craniofacial cephalometric measurements were obtained using CBCT. All measurements were assessed by analysis of covariance (ANCOVA) using Bonferroni post hoc pairwise comparison tests.ResultsANCOVA revealed no statistically significant differences in mandibular volume among the groups. SNA° and ANB° were significantly larger in the UCLA and BCLP groups than in the control group. SN-MP° was smallest in the UCLA group. Co-A in the UCLP group was shorter than in the UCLA and BCLP groups. Go-Gn was shortest in the UCLP and BCLP groups compared with the control group.ConclusionsThree-dimensional evaluation of craniofacial morphology using CBCT can provide valuable information on malocclusion and other dentoskeletal problems among patients with CLP.