To understand how CD8 expression is regulated during the transition process from CD4+8+ (CD4 and CD8 double positive, DP) to CD4-8+ (CD8 single positive, CD8SP) cells in the thymus, the involvement of Runx proteins in the alteration of chromatin configuration was investigated. Using the chromatin immunoprecipitation assay, we first demonstrated that Runx proteins bind to the stage-specific CD8 enhancer, as well as the CD4 silencer, in CD8SP thymocytes. Among Runx family members, Runx3 expression was initiated in DP thymocytes receiving a positive selection signal and increased in concert with differentiation to the CD8SP stage. Furthermore, reactivation of the CD8 gene, as well as CD4 silencing, was suppressed in positively selected thymocytes of Runx dominant-negative transgenic mice. These results suggest that Runx proteins, especially Runx3, are involved in lineage specification of CD8 T cells and provide important information for understanding the mechanism for the mutually exclusive expression of coreceptors in mature thymocytes.

Background and Aims: Peroral endoscopic myotomy (POEM) is an available treatment modalities for achalasia. The reported efficacy of POEM in the only prospective multicenter study was 82%; however, a retrospective multicenter study in Japan reported a higher efficacy rate of 95%. The aim of this study was to prospectively verify treatment outcomes after POEM at multiple facilities in Japan. Methods: This was a prospective single-arm trial of POEM for achalasia at 8 facilities in Japan between April 2016 and March 2018 to evaluate its safety and efficacy. Patients were re-evaluated at 3 months and up to 1 year after POEM. Results: Among the 233 patients with achalasia who underwent POEM, procedure-related adverse events occurred in 24 patients (10.3%), none of whom required surgical intervention. In the 207 patients satisfying the inclusion criteria, the efficacy rate of POEM, defined by an Eckardt score 3 at 1 year, was 97.4% (95% CI, 95.3%-99.7%). The Eckardt score decreased significantly from 6.6 AE 2.0 preoperatively to 1.1 AE 1.1, 1 year after POEM. Postoperative reflux esophagitis, severe reflux esophagitis, and symptomatic GERD were reported in 54.2%, 5.6%, and 14.7%, respectively, and proton pump inhibitors were administered in 21.1%. Conclusions: Our prospective multicenter study in Japan showed greater efficacy of POEM for achalasia compared with the results of a previous prospective multicenter study. POEM is safe and highly effective for at least 1 year.

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The variation of velocity and volume transport of the Tsugaru Warm Current (TWC) is investigated based on the data of continuous and cross‐sectional current monitoring in the Tsugaru Strait. During November 1999–March 2000, the structure of the velocity transection across the strait was almost stable in which the TWC occupied the central part of the strait, while the returning flows existed in the northern and southern part of the strait, and the velocity of these flows decreases with time. The volume transport of the TWC varies from 2.1 to 1.1 Sv, with the mean value of 1.5 Sv, following the variation of the TWC. The temporal variation of the volume transport shows a linear correlation with that of the sea level difference between the Japan Sea and the Pacific Ocean. The contribution of the sea level difference to the volume transport is estimated to be roughly 70%.

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Background/Purpose: The water jet technique dissects tissue while sparing cord-like structures such as blood vessels. The mechanism of such tissue-selective dissection has been unknown. The novel piezo actuator-driven pulsed water jet (ADPJ) system can achieve dissection with remarkably reduced water consumption compared to the conventional water jet; however, the system's characteristics and dissection capabilities on any organ have not been clarified. The purposes of this study were to characterize the physical properties of the novel ADPJ system, evaluate the dissection ability in swine organs, and reveal the mechanism of tissue-selective dissection. Methods: The pulsed water jet system comprised a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle. The peak pressure of the pulsed water jet was measured through a sensing hole using a pressure sensor. The pulsed water jet technique was applied on swine liver in order to dissect tissue on a moving table using one-way linear ejection at a constant speed. The dissection depth was measured with light microscopy and evaluated histologically. The physical properties of swine liver were evaluated by breaking strength tests using tabletop universal testing instruments. The liver parenchyma was also cut with three currently available surgical devices to compare the histological findings. Results: The peak pressure of the pulsed water jet positively correlated with the input voltage (R² = 0.9982, p < 0.0001), and this was reflected in the dissection depth. The dissection depth negatively correlated with the breaking strength of the liver parenchyma (R² = 0.6694, p < 0.0001). The average breaking strengths of the liver parenchyma, hepatic veins, and Glisson's sheaths were 1.41 ± 0.45, 8.66 ± 1.70, and 29.6 ± 11.0 MPa, respectively. The breaking strength of the liver parenchyma was significantly lower than that of the hepatic veins and Glisson's sheaths. Histological staining confirmed that the liver parenchyma was selectively dissected, preserving the hepatic veins and Glisson's sheaths in contrast to what is commonly observed with electrocautery or ultrasonic instruments. Conclusions: The dissection depth of liver tissue is well controlled by input voltage and is influenced by the moving velocity and the physical properties of the organ. We showed that the device can be used to assure liver resection with tissue selectivity due to tissue-specific physical properties. Although this study uses an excised organ, further in vivo studies are necessary. The present work demonstrates that this device may function as an alternative tool for surgery due to its good controllability of the dissection depth and ability of tissue selectivity.

Patients with residual cancer would have good prognosis by salvage esophagectomy in cases in which the cancer had not invaded to the adventitia at the time of chemoradiotherapy and surgery. Conversely, patients whose cancer was recurrent might benefit from salvage surgery if the cancer appears to be resectable. T and N status before chemoradiotherapy are not important factors in consideration of salvage esophagectomy in cases of recurrent cancer.