Use of Actigraphy for a Rat Behavioural Sleep Study

Previous studies of animal behavioural sleep is mainly divided into two study types, observation by video recording or counts by sensor, both of which require a complex environment and procedure. An actigraph unit is a commercially available product which can provide non-invasive monitoring human rest/activity cycles. The goal of this study was to evaluate whether actigraphy can be applied for analysing behavioural sleep in rats, since no reports have described utilization of the actigraphy unit for monitoring sleep of small animals. The actigraph unit was held on the chest of eight male rats by a loose elastic belt. The rats spent two days in a normal condition, followed by two days of sleep deprivation. Total counts measured by the actigraph could be clearly divided into two phases, sleep phase and awake phase, when the rats were kept in the normal cage. Next, the rats were moved into the sleep-deviation cage, and the total counts were significantly higher during daytime, indicating the successful induction of sleep deprivation. These results showed that the actigraphy unit monitored rest/activity cycles of rats, which will contribute to making sleep behaviour experiments easier

Autophagy promotes degradation of internalized collagen and regulates distribution of focal adhesions to suppress cell adhesion

Adhesion of cells to the extracellular matrix (ECM) via focal adhesions (FAs) is crucial for cell survival, migration, and differentiation. Although the regulation of FAs, including by integrins and the ECM, is important to cell behavior, how FAs are regulated is not well known. Autophagy is induced by both cell adhesion and cell detachment. Here, we showed that autophagosomes are located close to internalized collagen and paxillin, which is a well-known marker of FAs. Autophagy-deficient cells showed increased levels of internalized collagen compared with control cells. Moreover, paxillin exhibited a more peripheral distribution and the area of paxillin was increased, and adhesion-induced focal adhesion kinase signaling was impaired and adhesion was enhanced, in autophagy-deficient cells. These results suggest that autophagy suppressed cell adhesion by regulating internalized ECM and FAs

Propensity score-matching analysis to compare clinical outcomes of endoscopic submucosal dissection for early gastric cancer in the postoperative and non-operative stomachs

Abstract Background Endoscopic submucosal dissection (ESD) of the postoperative stomach (ESD-P) for early gastric cancer (EGC) is considered a technically difficult procedure. However, it is difficult to compare the outcomes of ESD-P and ESD of the non-operative stomach (ESD-N) because their baseline characteristics are different. Therefore, we aimed to compare the technical outcomes of ESD-P with those of ESD-N using a propensity score-matching analysis to compensate for the differences. Methods The chart records of 1046 patients with EGC who were treated with ESD between January 2004 and July 2016 at Kitakyushu Municipal Medical Center in Japan were reviewed in this retrospective study. Multivariate analyses and propensity score-matching were performed for age, sex, lesion location, lesion size, tumor invasion, tumor size, ulcer (scar), and operator skill. The primary outcome was procedure time. Secondary outcomes were percentages of en bloc, complete, and curative resections, and percentages of adverse events, which were evaluated between the two groups. Results Forty-one patients were in the ESD-P group and 1005 patients were in the ESD-N group. Propensity score-matching created 41 matched pairs. According to the adjusted comparisons, ESD-P required a significantly longer procedure time (85 min vs 51 min, p < 0.001). Other treatment outcomes showed an en bloc resection rate of 100% for both groups (p = 1) and complete resection rates of 95.1 and 97.6% (p = 1), curative resection rates of 90.2 and 90.2% (p = 1), perforation during ESD rates of 2.4 and 0% (p = 1), and postprocedure bleeding rates of 2.4 and 2.4% (p = 1) for the ESD-P and ESD-N groups, respectively. For the ESD-P group, lesions on the suture line or anastomotic site were significantly associated with longer procedure times (p = 0.038). Conclusions ESD-P was a more time-consuming procedure than ESD-N. However, ESD-P and ESD-N achieved high rates of curative resection with a low rate of adverse events for the treatment of EGC. ESD could be selected as the treatment for EGC even in the postoperative stomach provided that careful attention is given to lesions on the suture line or anastomotic site

Safety and Efficacy of the Noncessation Method of Antithrombotic Agents after Emergency Endoscopic Hemostasis in Patients with Nonvariceal Upper Gastrointestinal Bleeding: A Multicenter Pilot Study

Background and Aims. The present study aimed to clarify the safety and efficacy of the noncessation method of antithrombotic agents after emergency endoscopic hemostasis in patients with nonvariceal upper gastrointestinal bleeding (UGIB). Methods. In this multicenter, prospective, pilot study, we performed emergency endoscopic hemostasis for nonvariceal UGIB in patients taking antithrombotic agents and resumed the medications without a cessation period (group A). The clinical characteristics, types of antithrombotic agents, UGIB etiology, treatment outcome, and adverse events were evaluated. We used propensity score matching to compare treatment outcomes and adverse events with our previous cohort (group B) in whom antithrombotic agents were transiently discontinued after emergency endoscopic hemostasis. Results. Forty-three consecutive patients were prospectively enrolled. The main antithrombotic agents were low-dose aspirin and direct oral anticoagulants; 11 patients (25.6%) were taking multiple antithrombotics. Peptic ulcers were the main cause of bleeding (95.4%). Endoscopic hemostasis was successful in all patients and the incidence of rebleeding within a month was 7.0%. Propensity score matching created 40 matched pairs. Endoscopic hemostasis was performed by soft coagulation significantly more frequently in group A than in group B (97.5% versus 60.0%, P < 0.001). Neither the rebleeding rate within a month nor thromboembolic event rate was different between the two groups. However, the mean duration of hospitalization was significantly shorter in group A than in group B (8.6 ± 5.2 d versus 14.4 ± 7.1 d, P < 0.001). Conclusions. Antithrombotic agents possibly can be continued after successful emergency endoscopic hemostasis for nonvariceal UGIB

SPTLC2 variants are associated with early‐onset ALS and FTD due to aberrant sphingolipid synthesis

Abstract Objective Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early‐onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies. Methods Our research commenced with an in‐depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early‐onset ALS (onset age of <40 years). This involved whole‐exome sequencing, trio analysis, protein structure analysis, and sphingolipid measurements. Subsequently, we expanded our analysis to 62 probands with early‐onset ALS and further included 440 patients with adult‐onset ALS and 1163 healthy controls to assess the prevalence of identified genetic variants. Results We identified heterozygous variants in the serine palmitoyltransferase long chain base subunit 2 (SPTLC2) gene in patients with early‐onset ALS. These variants, located in a region closely adjacent to ORMDL3, bear similarities to SPTLC1 variants previously implicated in early‐onset ALS. Patients with ALS carrying these SPTLC2 variants displayed elevated plasma ceramide levels, indicative of increased serine palmitoyltransferase (SPT) activity leading to sphingolipid overproduction. Interpretation Our study revealed novel SPTLC2 variants in patients with early‐onset ALS exhibiting frontotemporal dementia. The combination of genetic evidence and the observed elevation in plasma ceramide levels establishes a crucial link between dysregulated sphingolipid metabolism and ALS pathogenesis. These findings expand our understanding of ALS's genetic diversity and highlight the distinct roles of gene defects within SPT subunits in its development