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While amplicon sequencing of 16S rRNA is a common method for studying microbial community, it has been difficult to identify genera and species using next-generation sequencers to examine some regions (e.g., V3–V4 of 16S rRNA) because of the short read lengths. However, the advent of third-generation sequencers has made it possible to analyze the full length of the 16S rRNA gene, which allowed for species level identification at low cost. In this study, we evaluated the accuracy of the identification with a third-generation sequencer, MinION from Oxford Nanopore Technologies, using nine indigenous bacteria that can pose problems with food poisoning and opportunistic infections as an example. We demonstrated that Enterococcus faecalis and Enterococcus hirae could be identified at the species level with an accuracy of 96.4% to 97.5%. We also demonstrated that the absolute counts of various bacteria could be determined by spiking the sample with a bacterium as an internal standard. Then, we tested whether this convenient bacterial identification method could evaluate the antibiotic sensitivities of multiple bacteria simultaneously. In order to evaluate antimicrobial susceptibility, a mock community, an artificial mixture of the nine bacterial strains, was prepared and cultured in the presence of the antibiotics ofloxacin or chloramphenicol, and the 16S rRNAs were analyzed by using Nanopore sequencer. We confirmed that antibiotic-induced cell count reductions could be measured simultaneously by quantifying the abundances of various bacteria in the mock community before and after culture. It was thus shown that the antibiotic sensitivities of multiple bacteria could be evaluated simultaneously, with distinction made between bactericidal action and bacteriostatic action. This methodology would allow rapid evaluation of antibiotic activity spectrum at the species level containing a wide variety of bacteria, such as biofilm bacteria and gut microbiota.

Hepatocyte growth factor (HGF) receptor, also known as Met, is a member of the receptor tyrosine kinase family. The Met–HGF interaction regulates various signalling pathways involving downstream kinases, such as Akt and Erk. Met activation is implicated in wound healing of tissues via multiple biological responses triggered by the above-mentioned signalling cascade. Here we report the development of artificial Met-activating dimeric macrocycles. We identify Met-binding monomeric macrocyclic peptides by means of the RaPID (random non-standard peptide integrated discovery) system, and dimerize the respective monomers through rational design. These dimeric macrocycles specifically and strongly activate Met signalling pathways through receptor dimerization and induce various HGF-like cellular responses, such as branching morphogenesis, in human cells. This work suggests our approach for generating dimeric macrocycles as non-protein ligands for cell surface receptors can be useful for developing potential therapeutics with a broad range of potential applications. Activation of the Met receptor by hepatocyte growth factor requires Met receptor dimerization. Here, the authors identify Met-binding peptide macrocycles that, in a dimeric form as a result of chemical crosslinking, induce Met receptor dimerization and activation in cultured human cells.

BackgroundIntravenous administration of magnesium with a short hydration regimen is recommended for patients receiving high-dose cisplatin to protect against cisplatin-induced nephrotoxicity. However, the optimal dose of magnesium supplementation has not been clarified. The aim of this trial was to investigate the safety and efficacy of a short hydration regimen with 20 mEq of magnesium supplementation for lung cancer patients receiving cisplatin-based chemotherapy.MethodsThe key eligibility criteria included cytologically or histologically diagnosed lung cancer, candidacy for cisplatin-based (≥ 60 mg/m2) chemotherapy or chemoradiotherapy, no prior chemotherapy, aged 20–75 years, and adequate renal function. Cisplatin was administered with pre-hydration with 20 mEq of magnesium sulfate. Mannitol was administered just before cisplatin infusion to enforce diuresis. The primary endpoint was the proportion of patients who underwent cisplatin-based chemotherapy with a short hydration regimen with 20 mEq of magnesium supplementation without a grade 2 or higher elevation in creatinine.ResultsForty patients with a median age of 66 years (range 35–74) were prospectively enrolled. Median baseline creatinine was 0.71 mg/dL. Median dose of cisplatin in the first cycle was 80 mg/m2. In the first cycle, no patients developed grade 2 creatinine toxicity. During the treatment period, one patient developed grade 2 creatinine elevation; thus, the proportion of patients without a grade 2 or higher elevation in creatinine was 97.5% (95% confidence interval 86.8–99.9).ConclusionA short hydration regimen with 20 mEq of magnesium supplementation is safe and feasible for patients with lung cancer receiving cisplatin-based chemotherapy.

Afferent loop syndrome is a complication that occurs after the Billroth Ⅱ reconstruction or Roux-en-Y reconstruction and can also be caused by enteroliths. We experienced a case of duodenal perforation due to afferent loop syndrome caused by an enterolith, in which surgical removal of the enterolith and decompression of the duodenum were effective. A 73-year-old female who underwent distal gastrectomy and Roux-en-Y reconstruction for gastric cancer 14 years ago came to the hospital with acute abdominal pain and underwent emergency surgery for afferent loop syndrome and duodenal perforation due to enterolith. The patient underwent removal of the enterolith, drain placement, and placement of a decompression tube in the duodenum. Postoperatively, percutaneous drainage of the intra-abdominal abscess was necessary, but the patient was saved without reoperation. Afferent loop perforation may occur with obstruction due to enteroliths, and the surgical insertion of a tube to decompress the afferent loop is effective.

Pediatric pouchitis has no established treatment strategy, and management is particularly challenging in recurrent or antibiotic-refractory cases. Tumor necrosis factor alpha (TNF-α) and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) are established and emerging therapeutic targets, respectively, in adult ulcerative colitis (UC) and pouchitis; however, their expression profiles and clinical relevance in pediatric pouchitis remain unclear. Therefore, we evaluated the pathological and clinical significance of TNF-α and MAdCAM-1 in pediatric pouchitis. We performed immunohistochemical analysis of surgically resected ileal tissues and subsequent pouch biopsy specimens obtained from 10 pediatric patients with UC. Paired pouchitis biopsies were collected during both active (high pouchitis disease activity index, PDAI) and improved (low PDAI) phases. TNF-α, MAdCAM-1, and immune cell markers (CD68, CD163, and CD8) in the mucosal stroma were quantitatively assessed using HALO image analysis. Compared with baseline ileal tissues, pouchitis specimens showed increased MAdCAM-1-positive vasculature and infiltration of CD68- and CD163-positive cells. In paired specimens, MAdCAM-1, TNF-α, and CD68 expression was significantly reduced in low-PDAI tissues. MAdCAM-1 and TNF-α expression was positively correlated with inflammatory cell infiltration. This exploratory study provided the first histological evidence that MAdCAM-1 and TNF-α could be upregulated in pediatric pouchitis and associated with disease severity, highlighting the pathological relevance of adult UC therapeutic targets in this setting.

Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionally. However, the association of PD-L1/DSB/IRF-1 with sporadic colorectal cancer (SCRC), and UC-associated dysplasia/colitic cancer, remains elusive. Therefore, we investigated the significance of the PD-L1/DSB repair pathway using samples from 17 SCRC and 12 UC patients with rare UC-associated dysplasia/colitic cancer cases by immunohistochemical analysis. We compared PD-L1 expression between patients with SCRC and UC-associated dysplasia/colitic cancer and determined the association between PD-L1 and the CD8+ T-cell/DSB/IRF-1 axis in UC-associated dysplasia/colitic cancer. PD-L1 expression in UC and UC-associated dysplasia/colitic cancer was higher than in normal mucosa or SCRC, and in CD8-positive T lymphocytes in UC-associated dysplasia/colitic cancer than in SCRC. Moreover, PD-L1 upregulation was associated with γH2AX (DSB marker) and IRF-1 upregulation in UC-associated dysplasia/colitic cancer. IRF-1 upregulation was associated with γH2AX upregulation in UC-associated dysplasia/colitic cancer but not in SCRC. Multicolour immunofluorescence staining validated γH2AX/IRF-1/PD-L1 co-expression in colitic cancer tissue sections. Thus, immune cell-induced inflammation might activate the DSB/IRF-1 axis, potentially serving as the primary regulatory mechanism of PD-L1 expression in UC-associated carcinogenesis.

Extracorporeal membrane oxygenation (ECMO) cannulas inserted through the femoral vein can stray into the ascending lumbar vein. No case has been reported in which the cannula has penetrated the common iliac vein and entered the abdominal cavity. A 52-year-old man was brought to the emergency room with ventricular fibrillation, and the cannula inserted from the left femoral vein for extracorporeal cardiopulmonary resuscitation penetrated the common iliac vein, passed between the pancreas and horizontal portion of the duodenum, and entered the abdominal cavity to reach the hepatic left lateral lobe. The cannula was removed, and organ damage was confirmed through laparotomy. When it is necessary to remove a cannula that has penetrated a vessel, surgical removal is preferable to evaluate the damage and prevent complications associated with removal.

We have developed a Yb-doped fiber amplifier (YDFA) using fusion splicing, and characterized its performance with numerical simulation, achieving a continuous output of above 10W of 1064nm light. The device has been conceptualized to have a configuration as simple as possible; a strategy for using fiber amplifiers in harsh environments where quick repairs and replacements may become necessary at unexpected times.

Type IV hiatal hernia of the esophagus is characterized by herniation of the stomach and associated organs, such as the spleen, large and small bowel, and pancreas, through the esophageal hiatus. It is a relatively rare form of hiatal hernia that sometimes requires emergency surgery due to gastric incarceration, volvulus, and strangulation. Of these, small bowel obstruction is extremely rare and requires surgery. We report the case of an 83-year-old woman who was admitted to the hospital for small bowel obstruction caused by an ileum that had incarcerated the esophageal hiatus; emergency laparoscopic surgery was performed.

Previous studies have examined bowel preparation as a measure to reduce surgical site infection (SSI) rates. This retrospective study aimed to identify the risk factors for SSI in right-sided colon cancer surgery using intracorporeal anastomosis (IA). We focused on perioperative factors, including the bowel preparation method, to clarify the impact of preoperative mechanical bowel preparation (MBP) and oral antibiotics (OA) on SSI incidence. Patients (  = 150) with right-sided colon cancer who underwent elective laparoscopic or robot-assisted colectomy (2019 and 2023) were included. Potential risk factors for SSI were examined using univariate and multivariate analyses. The overall incidence of SSI was 11 (7.3%) cases, with eight (5.4%) cases classified as incision site SSI and three (1.9%) as organ/space SSI. Univariate analysis showed that OA (  < 0.001) and MBP (  = 0.002) significantly reduced the SSI rate. Multivariate analysis identified OA as an independent risk factor (hazard ratio, 0.142; 95% confidence interval, 0.025-0.827;  = 0.025). Patients with SSI had longer postoperative hospital stays compared to those without SSI (median 9 vs. 8 days,  = 0.012). On postoperative day 1, the group receiving OA had significantly lower white blood cell count (9390 vs. 10 900/μL,  = 0.005) and C-reactive protein levels (3.81 vs. 7.83 mg/dL,  < 0.001) compared to those in the group not receiving OA. Preoperative administration of OA in laparoscopic or robot-assisted right-sided colon cancer surgery with IA may help decrease the incidence of SSI.