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Bifidobacterium pseudocatenulatum grows well in the early stages of cultivation in medium containing sucrose (Suc), whereas its growth in medium containing the analogue disaccharide N-acetylsucrosamine (SucNAc) tends to exhibit a considerable delay. To elucidate the cause of this phenomenon, we investigated the proliferation pattern of B. pseudocatenulatum in medium containing D-glucose (Glc) and SucNAc and identified the enzyme that degrades this disaccharide. We found that B. pseudocatenulatum initially proliferates by assimilating Glc, with subsequent growth based on SucNAc assimilation depending on production of the β-fructofuranosidase, which can hydrolyze SucNAc, after Glc is completely consumed. Thus, B. pseudocatenulatum exhibited a diauxic growth pattern in medium containing Glc and SucNAc. In contrast, when cultured in medium containing Glc and Suc, B. pseudocatenulatum initially grew by degrading Suc via the phosphorolysis activity of Suc phosphorylase, which did not react to SucNAc. These observations indicate that B. pseudocatenulatum proliferates by assimilating Suc and SucNAc via different pathways. The β-fructofuranosidase of B. pseudocatenulatum exhibited higher hydrolytic activity against several naturally occurring Suc-based tri- or tetrasaccharides than against Suc, suggesting that this enzyme actively catabolizes oligosaccharides other than Suc.

Supplementary Figures 9-10 from Regulation of Human Nitric Oxide Synthase 2 Expression by Wnt β-Catenin Signaling

Nitric oxide (NO·), an important mediator of inflammation, and β-catenin, a component of the Wnt–adenomatous polyposis coli signaling pathway, contribute to the development of cancer. We have identified two T-cell factor 4 (Tcf-4)-binding elements (TBE1 and TBE2) in the promoter of human inducible NO synthase 2 (NOS2). We tested the hypothesis that β-catenin regulates human NOS2 gene. Mutation in either of the two TBE sites decreased the basal and cytokine-induced NOS2 promoter activity in different cell lines. The promoter activity was significantly reduced when both TBE1 and TBE2 sites were mutated (P < 0.01). Nuclear extract from HCT116, HepG2, or DLD1 cells bound to NOS2 TBE1 or TBE2 oligonucleotides in electrophoretic mobility shift assays and the specific protein-DNA complexes were supershifted with anti-β-catenin or anti-Tcf-4 antibody. Overexpression of β-catenin and Tcf-4 significantly increased both basal and cytokine-induced NOS2 promoter activity (P < 0.01), and the induction was dependent on intact TBE sites. Overexpression of β-catenin or Tcf-4 increased NOS2 mRNA and protein expression in HCT116 cells. Lithium chloride (LiCl), an inhibitor of glycogen synthase kinase-3β, increased cytosolic and nuclear β-catenin level, NOS2 expression, and NO· production in primary human and rat hepatocytes and cancer cell lines. Treatment with Wnt-3A-conditioned medium increased β-catenin and NOS2 expression in fetal human hepatocytes. When administered in vivo, LiCl increased hepatic β-catenin level in a dose-dependent manner with simultaneous increase in NOS2 expression. These data are consistent with the hypothesis that β-catenin up-regulates NOS2 and suggest a novel mechanism by which the Wnt/β-catenin signaling pathway may contribute to cancer by increasing NO· production. (Cancer Res 2006; 66(14): 7024-31)

Supplementary Figure 1 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

Supplementary Figure 4 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

Supplementary Figure 3 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

Supplementary Table 1 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

Supplementary Materials & Methods from Regulation of Human Nitric Oxide Synthase 2 Expression by Wnt β-Catenin Signaling

Supplementary Figure 7 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

Supplementary Figure 5 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

Supplementary Figure 2 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

Supplementary Figure 6 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence

The number of laparoscopic sleeve gastrectomies (LSGs) performed in patients with obesity who are eligible for bariatric and metabolic surgery is currently much lower in Japan than in other countries. Considering the large number of potential patients with obesity and type 2 diabetes and the unique Japanese national health insurance system that guarantees fair healthcare delivery, there is room to increase the number of LSGs in Japan in the near future. However, strict health insurance regulations may limit access to mandatory devices needed to treat postoperative complications, such as staple line leakage, which can cause severe morbidity and even mortality. Therefore, understanding the pathogenesis and treatment options for this complication is crucial. This article examined the current situation in Japan and its impact on staple line leakage management, including the role of endoscopic treatment in reducing reoperation. The authors suggest increasing education and collaboration between healthcare professionals to optimize management and improve patient outcomes.

Among Asian countries, laparotomic and laparoscopic bariatric surgeries were introduced in Japan after its establishment in Taiwan. However, despite high prevalence of potential patients with obesity and diabetes, the wider incorporation of surgery into treatment regimen has been stalling for decades in Japan. While the unique Japanese national health insurance system has guaranteed fair healthcare delivery, it might have worked as a barrier to the development of bariatric and metabolic surgeries (BMS). The present article reviews the status of BMS in Japan and discusses recent issues related to its use. To focus on and identify the major obstacles inhibiting the widespread use of BMS, we have comprehensively covered some major areas including the insurance system, surgical indication, accreditation and training system, original research, and national registry.

The results from the phase 3 study that evaluated the efficacy and safety of tedizolid phosphate, an oxazolidinone drug, for the treatment of gram-positive ventilated hospital-acquired bacterial pneumonia (vHABP)/ventilator-associated bacterial pneumonia (VABP) compared with linezolid (VITAL study), have been previously reported. We conducted a subgroup analysis to report the data obtained from Japanese patients enrolled in this study.Patients aged ≥18 years with vHABP/VABP likely to be caused by gram-positive cocci were randomized 1:1 to tedizolid phosphate 200 mg once daily for 7 days or linezolid 600 mg twice daily for 10 days. In both treatment groups, patients with concurrent gram-positive bacteremia were treated for 14 days. Primary efficacy endpoints were day 28 all-cause mortality (ACM) and investigator-assessed clinical response at test-of-cure (TOC) in the intention-to-treat population. Safety outcomes included assessment of treatment-emergent adverse events.Fifty-three Japanese patients were randomized at received study drug (tedizolid, n = 28; linezolid, n = 25). Demographics and characteristics were generally similar between treatment groups. Rates of day 28 ACM were 10.7% and 20.0% with tedizolid and linezolid, respectively (difference, 9.3%; 95% CI, -10.1 to 28.7). Rates of investigator-assessed clinical cure at TOC were 78.6% and 72.0% with tedizolid and linezolid, respectively (difference, 6.6%; 95% CI, -16.7 to 29.8). Tedizolid phosphate was generally well tolerated and no new safety concerns were observed in the Japanese subgroup.The results from this subgroup analysis suggest generally favorable efficacy and safety of tedizolid in adult Japanese patients with vHABP/VABP. (ClinicalTrials.gov identifier: NCT02019420).

Considerable individual differences are widely observed in the sensitivity to opioid analgesics. We focused on rs12496846, rs698705, and rs10052295 single-nucleotide polymorphisms (SNPs) in the

Short tandem repeats (STRs) and variable number of tandem repeats (VNTRs) that have been identified at approximately 0.7 and 0.5 million loci in the human genome, respectively, are highly multi-allelic variations rather than single-nucleotide polymorphisms. The number of repeats of more than a few thousand STRs was associated with the expression of nearby genes, indicating that STRs are influential genetic variations in human traits. Analgesics act on the central nervous system via their intrinsic receptors to produce analgesic effects. In the present study, we focused on STRs and VNTRs in the

Characteristics of Staphylococcus aureus infections include biofilm formation, leading to the spread of bacteria to the bloodstream causing sepsis and metastatic infections. In particular, in methicillin-resistant S. aureus (MRSA) infections, biofilm formation critically hampers treatment and causes poor prognosis. We explored the biofilm formation of MRSA in the presence or absence of plasma and compared morphological characteristics, accumulation of antibiotics, and resistance to bactericidal activity, using continuous optimizing confocal reflection microscopy. Addition of plasma significantly increased biofilm formation, which is characterized by an uneven surface and aggregation of bacteria (hereafter plasma biofilm). The flow-cell system, which enabled a continuous supply of plasma, accelerated biofilm formation in both the tested strains of MRSA (BAA1556 and N315). Accumulation of green fluorescence-labeled vancomycin was observed within 5 minutes in the plasma-free biofilm, but not in the plasma biofilm. Delay of accumulation was also observed for daptomycin in plasma biofilm. Plasma biofilm bacteria were more resistant to anti-MRSA antibiotics than plasma-free biofilm bacteria. These data demonstrate that the plasma biofilm of S. aureus is substantially different from the plasma-free biofilm. Plasma biofilm, especially in the flow-cell system, could be a clinically relevant model to analyze MRSA infections and treatment.

Background Although preoperative detection of pleural adhesions is important in thoracic surgery, it is not widely performed. We report the availability of a pocket-sized ultrasound device for the preoperative detection of pleural adhesions. Methods Between September 2019 and September 2020, pleural adhesions were assessed preoperatively using a pocket-sized ultrasound device in 62 patients who underwent thoracic surgery. Evaluations were performed using the Vscan Dual Probe on the wards or just before surgery in the operating theater. We used a linear probe to scan the chest wall where the incision was scheduled, and evaluated the sliding sign. We compared ultrasound results with intraoperative findings. Results Of the 62 patients, the sliding sign was observed in 58 patients, 56 of whom demonstrated no pleural adhesions intraoperatively. The sensitivity was 96.6%. Four patients were negative for the sliding sign; of these, three had pleural adhesions and one did not. The specificity was 75.0%. Among all 62 patients, the diagnostic accuracy of ultrasound for pleural adhesions was 95.2%. False negatives were caused by loose adhesions. False positives were caused by the absence of vertical lines on ultrasound. Accuracy was not influenced by the timing of the test. Conclusions A pocket-sized ultrasound device was useful for the preoperative detection of pleural adhesions in thoracic surgery.

Background Current medical treatments can achieve remission of ulcerative colitis (UC). Surgery is required when potent drug treatment is ineffective or when colon cancer or high-grade dysplasia develops. The standard procedure is restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis, commonly performed as two- or three-stage RPC with diverting ileostomy. Postoperative stoma outlet obstruction (SOO) is frequent, but the causes are not well known. Aim To identify the risk factors for SOO after stoma surgery in patients with UC. Methods We retrospectively reviewed the files of 148 consecutive UC patients who underwent surgery with stoma construction. SOO was defined as small bowel obstruction symptoms and intestinal dilatation just below the penetrating part of the stoma on computed tomography. Patients were divided into two groups: Those who developed SOO within 30 d after surgery and those who did not. Patient characteristics, intraoperative parameters, the stoma site, and rectus abdominis muscle thickness were collected. Moreover, we identified the patients who repeatedly developed SOO. Univariate and multivariate analyses were performed to identify risk factors for SOO and recurring SOO. Results Eighty-nine patients who underwent two-stage RPC were included between January 2008 and March 2020. Postoperatively, SOO occurred in 25 (16.9%) patients after a median time of 9 d (range 2-26). Compared to patients without SOO, patients with SOO had a significantly higher rate of malignant tumors or dysplasia (36.0% vs 17.1%, P = 0.032), lower total glucocorticoid dose one month before surgery (0 mg vs 0 mg, P = 0.026), higher preoperative total protein level (6.8 g/dL vs 6.3 g/dL, P = 0.048), higher rate of loop ileostomy (88.0% vs 55.3%, P = 0.002), and higher maximum stoma drainage volume (2300 mL vs 1690 mL, P = 0.004). Loop ileostomy (OR = 6.361; 95%CI 1.322-30.611; P = 0.021) and maximum stoma drainage volume (OR = 1.000; 95%CI 1.000-1.001; P = 0.015) were confirmed as independent risk factors for SOO. Eighteen patients with SOO were treated conservatively without recurrence (sSOO group). Seven (28.0%) patients repeatedly developed SOO (rSOO group) during the observation period. A significant difference was observed in the rectus abdominis muscle thickness between the two groups (sSOO 9.3 mm, rSOO 12.7 mm, P = 0.006). Muscle thickness was confirmed as an independent risk factor for recurring SOO (OR = 2.676; 95%CI 1.176-4.300; P = 0.008). Conclusion In this study, high maximum stoma drainage volume and loop ileostomy are independent risk factors for SOO. Additionally, among patients with a thick rectus abdominis muscle, the risk of SOO recurrence is high.

Introduction. Empirical vancomycin (VAN) treatment failure for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia, with significantly higher mortality, has been reported for MRSA strains with reduced VAN susceptibility. Aim. Our goal was to study the effect of sub-culture on VAN minimum inhibitory concentration (MIC) values compared to direct susceptibility of MRSA-positive blood cultures. Methodology. Using 19 MRSA-positive blood cultures and 19 seeded MRSA-positive blood cultures, we compared the VAN MICs from direct susceptibility testing of MRSA-positive blood cultures and MRSA sub-cultured from positive blood cultures. Results. In comparing direct VAN MICs from MRSA-positive blood cultures and standard agar dilution, nearly half of the MICs from agar dilution were lower, with one sample decreasing from 1.5 to 0.75 µg ml−1. Furthermore, in seeded blood cultures, 80 % or more showed lower values from standard agar dilution compared to direct VAN MICs. Conclusion. Our results reveal a trend towards lower MICs after positive blood culture isolates are sub-cultured. Some clinical failures among MRSA infections treated with VAN may result from this phenomenon.

Aim Cancer pain impairs not only physical functions but also social functions and roles. Consequently, the overall health‐related quality of life of patients with cancer pain deteriorates. Opioid analgesics are recommended for treating moderate to strong cancer pain. Advances in human genome research have fueled a growing interest to understand individual differences in responsiveness to opioid analgesics. This study aimed to explore and identify novel loci for genes predisposing an individual to opioid analgesic responsiveness. Methods A total of 71 cancer patients rated their pain on an 11‐point numerical rating scale twice before and after increasing opioid analgesics. A genomewide association study focusing on single nucleotide polymorphisms (SNPs) was conducted to associate pain decrease with increased dosage of opioid analgesics based on weight (ie, responsiveness to opioid analgesics). A genomewide significance (P < 5E‐8) was set for multiplicity of analyses to control for false positives. Results Two SNPs passed the genomewide threshold for significance. One exonic SNP (rs1641025) was located in the ABAT [4‐aminobutyrate aminotransaminase (GABA transaminase)] gene on chromosome 16. The other SNP (rs12494691) was located on chromosome 3, which was not associated with any known genes. These SNPs were not associated with opioid‐related adverse effects. Conclusions Our results preliminarily suggest that both SNPs might be potential candidate loci for responsiveness to opioid analgesics, and GABA transaminase might be a possible target for developing adjuvant pharmacotherapy with opioid analgesics in adjuvant pharmacotherapy. Our results should be validated in a large‐scale study with a larger sample size., A genome‐wide association study revealed two candidate single nucleotide polymorphisms for responsiveness to opioid analgesics in patients with cancer pain, one of which locates on the GABA transaminase gene.

Gastric leakage and stricture are challenging complications of sleeve gastrectomy (SG). Failure of endoscopic intervention necessitates revision surgery. We describe two cases in which proximal gastrectomy with double tract reconstruction (PG with DTR) was performed in patients with chronic gastric fistula and twisted gastric tube after SG. Following resection of the affected part of the proximal stomach, reconstruction was achieved with three anastomoses [esophagojejunostomy (EJ), gastrojejunostomy (GJ), and jejunojejunostomy]. DTR provides two exit routes, the remnant stomach and the distal jejunum. The GJ was created 15 cm below the EJ with a stoma 10 mm in diameter, which can pass a standard endoscope. Both cases were a success without any short-term complications. PG with DTR could be an alternative option for refractory complications of SG.

Transverse sinus-sigmoid sinus (TS-SS) dural arteriovenous fistula (dAVF) is common type of dAVF, on the other hand, anterior condylar confluence (ACC) dAVF is relatively rare. There has been no report presenting patients with TS-SS dAVF and ACC dAVF identified simultaneously yet. We present a case of TS-SS dAVF and ACC dAVF that developed subcortical hemorrhage of left temporal lobe. A 66-year-old woman with no past history was transferred to our hospital for sudden-onset consciousness disturbance, and was urgently admitted after the detection of a subcortical hemorrhage in the left temporal lobe. We suspected a dAVF based on magnetic resonance angiography and performed digital subtraction angiography (DSA). DSA revealed that the left occipital artery, left ascending pharyngeal artery, left middle meningeal artery, left tentorial artery, and posterior meningeal artery flowed into the TS-SS and ACC. DSA also showed outflow from the TS-SS to the brain surface through the vein of Labbe and the vein of Trolard. We performed transvenous embolization to prevent re-bleeding, she was then discharged from our hospital and her remaining sensory aphasia gradually improved. In the present study, the active investigation to determine the cause of subcortical hemorrhage led to a definitive diagnosis. The combination of ACC dAVF and TS-SS dAVF has not been reported thus far and this is considered a valuable case.

Methicillin-resistant Staphylococcus aureus (MRSA) with decreased susceptibility to daptomycin (DAP) were isolated from 4 patients receiving DAP from November 2013 to May 2014. These patients were treated with DAP for more than 7 days in all the cases. The pulsed-field gel electrophoresis (PFGE) patterns for MRSA isolates recovered from each patient pre- and post-DAP therapy were identical. Sequencing of mprF detected 2 amino acid substitutions (T345I or L826F) in 2 of the isolates. These results suggest that in vivo MRSA was resistant to DAP during DAP therapy. Furthermore, the MICs for DAP can vary by±1 dilution depending on the susceptibility test. When testing DAP susceptibility, there is a need to monitor reproducibility using different susceptibility tests, including the CLSI method.

Pro- and anti-inflammatory cytokines (adipokines) associated with adipose tissue can modulate inflammatory processes and lead to systemic inflammatory conditions such as metabolic syndrome. In the present pilot study, we investigated 3 major adipokines (leptin, adiponectin, and resistin) and 2 nonspecific proinflammatory cytokines (tumor necrosis factor α and interleukin-6) with regard to their association with postoperative pain intensity.We analyzed a total of 45 single-nucleotide polymorphisms of the adipokines in 57 patients with postlaparotomy pain. We adjusted for multiple testing to reduce the chance of false-positive results by controlling the false discovery rate. Serum levels of the adipokines and proinflammatory cytokines were measured in another 36 patients undergoing laparotomy. A stepwise multiple linear regression analysis using these measurements and opioid dosages as independent variables was performed to explore the factors associated with postoperative pain.Only 1 variant of the resistin gene (rs3745367) demonstrated a significant association with postoperative pain (P.002). Patients exhibiting homozygosity for the minor alleles (n = 7; numerical rating scale [NRS], 2.3 ± 1.3) demonstrated lower pain intensity compared with those exhibiting homozygosity for the major alleles (n = 29; NRS, 3.8 ± 1.0; P = .004) and heterozygosity for the minor alleles (n = 21; NRS, 4.2 ± 0.8; P.001). Only serum resistin levels showed a positive association with postoperative pain.A genetic variant of resistin and serum resistin levels were associated with postoperative pain intensity, while other adipokines and cytokines exhibit no such association. Resistin can alter the inflammatory responses in postoperative wounds, although it could be a determinant factor that is independent of inflammatory processes. Resistin may be a novel marker for postoperative pain intensity.

A 78-year-old man underwent an upper gastrointestinal endoscopy for evaluation of epigastralgia. Endoscopy revealed a bulky type 3 tumor in the lesser curvature of the upper body. A biopsy showed a poorly differentiated adenocarcinoma with signet ring cell carcinoma. Additionally, abdominal computed tomography(CT)showed bulky lymph node metastases leading to a diagnosis of cT3N2M0, Stage III A carcinoma. Following administration of 2 courses of neoadjuvant chemotherapy (NAC)using S-1/cisplatin(CDDP), CT revealed significant regression of the primary lesion and lymph nodes. Eventually, laparoscopic total gastrectomy was performed. Histopathologically, almost all viable cancer cells had been cleared from the primary lesion, and no cancer cells were found in the lymph nodes, which indicated a pathological partial response(Grade 2). NAC could be a valid option for the treatment of advanced gastric cancer.

Background We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients. Methods Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were completion of the scheduled adjuvant chemotherapy over 12 months, and the secondary endpoints were relative total administration dose, toxicity, and 3-year disease-free survival. Results From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The planned S-1 administration over 12 months was accomplished to 28 patients in 38 arm A patients (73.7%) and to 18 patients in 40 arm B patients (45.0%, p = 0.01). The average relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). Grade 1–3 elevation of bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine transaminase were more frequently recorded in arm A than in arm B. The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94). Conclusions The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher completion rates over 12 months (p = 0.01) and relative dose intensity of S-1 (p = 0.01). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1–3 elevation of bilirubin. Trial registration This randomized multicenter study was retrospectively registered with the UMIN-CTR (UMIN000016086, registration date December 30, 2014).

Background Despite the widespread use of opioids for the treatment of cancer pain, results from several surveys consistently show that pain is still prevalent in some patients with malignant diseases. The purinergic P2Y12 receptor is a primary site leading to microglial activation and hyperalgesic pain behaviors and is considered a key regulator in the prevention of the aggravation of clinical pain conditions. Genetic variability in the P2RY12 gene may contribute to individual differences in pain and opioid sensitivity. Methods We genotyped 31 single nucleotide polymorphisms (SNPs) throughout the P2RY12 gene and compared genotypes against pain measurements and opioid requirements in Japanese cancer pain patients (N = 90). The most promising SNP association with pain severity was validated by genotyping an additional postoperative pain patient cohort (N = 355). Results Five SNPs (rs3732765, rs9859538, rs17283010, rs11713504, and rs10935840) of the P2RY12 gene were significantly associated with cancer pain severity, although opioid requirements were comparable in each genotype of the five SNPs. The alleles of these SNPs represented one absolute linkage disequilibrium block of the P2RY12 gene. In the second association study of postoperative pain, subjects carrying the minor T allele of the rs3732765 SNP demonstrated more intense 24-hour postoperative pain compared with subjects not carrying this allele although total 24-hour postoperative opioid consumptions based on weight were comparable. Conclusions Polymorphisms of the P2RY12 gene may predict individual differences in both cancer and postoperative pain severity; this might be caused by functional alteration of nociceptive neurons through neuron-glia interaction.

Japan is facing the problem of a sharp decline in the number of births, and a significant reduction in young population. In such a situation, in order to maintain the school size based on the current school system, it is necessary to promote further consolidation of schools. However, with only consolidation, it is impossible to guarantee the educational environment and education conditions in all regions. In addition, the presence of a school and children in the region are the lifeblood of the local community. School closures due to depopulation causes a vicious cycle that leads to further depopulation. Therefore, it is necessary to maintain a small school by improving budget, and to compensate for the disadvantages of small schools by building a network of small schools. Chain schools and package schools are specific methods to solve this problem. In the chain schools, we make use of economies of scale through the collaboration of multiple small schools, and ensure a variety of learning. The chain schools are school form for both educational diversity and economic efficiency. In the package schools, from the point of view of one−stop solution, we establish a kindergarten, a welfare facility, and a social education facility attached to the school, and we integrate the services of each facility. The package schools are school form that can deepen each function through the mutual exchange of various facilities.

In 1830, at the American Institute of Instruction, Wm. C. Woodbridge introduced the context of School Music Education that had been practiced in countries like Germany and Switzerland and proposed that School Music Education should also be implemented in the United States. Based on the information shared by Woodbridge, L. Mason released publications such as the Singing Book and Manual for Instruction in the Elements of Vocal Music, thereby launching instructions of vocal music to children in church choir groups and at private schools. In 1833, the Boston Academy of Music was founded by people who were interested in School Music Education and Church Music, marking the beginning of organizational research and educational activities of instruction in vocal music. The Boston Academy of Music, in 1836, filed a memorial to the Boston School Committee requesting the study and consideration of School Music Education. In February 1837, the Boston School Committee set up a subcommittee to investigate the subject of introducing vocal music instruction into the public schools and commissioned T. Kemper Davis, S. K. Lothrop and J. Field to report on the results of the investigation. Upon the submission of the Davis Report by this subcommittee, careful discussion took place based on the report and a decision was reached to perform the experiment at four public schools. However, the Boston City Council did not approve the appropriation for the experiment, so Mason conducted the experimental education and revealed its achievements without compensation. As a result, the School Music Education in the U.S. was authorized for the first time in Boston public schools in August 28, 1838. The present paper deliberated on the influence that the Davis Report had through a study of materials such as the Records of School Committee of Boston, the Minutes of a Meeting of the Board of Aldermen and newspaper articles. As a consequence, it clarified that the Davis Report not only rationally persuaded the raison d’etre of vocal music instruction in schools, but also spurred the momentum to concretely demonstrate the importance and practicability of vocal music instruction.

Background The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients. Methods This was a single-center retrospective study of 64 CRC patients who underwent FOLFOX therapy at the Toho University Sakura Medical Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group), whereas the additional 35 patients (non-OXY group) were not given oxycodone during the FOLFOX treatment course. The incidence and severity of OIPN and the number of FOLFOX cycles were measured and compared between the two groups. Neurological toxicities were assessed according to the Common Terminology Criteria for Advanced Events, version 3.0. Results All study patients had OIPN. Most patients experienced grade 1 or 2 sensory neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non-OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy, whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY and non-OXY groups were 13 (range, 6–46) and 7 (range, 2–18), respectively (P

We report a unique case of giant obstructing inflammatory polyposis associated with ulcerative colitis (UC). A 25-year-old Japanese man with an UC history of 2 years and 6 months was referred to our institution because of diarrhea and melena. His computed tomography scan showed marked dilation of the transverse and descending colon; therefore, we performed total colectomy. Macroscopic evaluation of the excised specimen indicated constricting lesions with giant polyposis in the transverse and descending colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregular ulcers. Histologic evaluation of the excised specimen indicated transmural inflammation with a thickened proper muscular layer overlaid with inflammatory polyposis. Based on these data, a diagnosis of giant inflammatory polyposis should be considered in patients who have had UC. Although giant inflammatory polyposis is considered benign, surgical treatment may be indicated to avoid serious complications.