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Guanylate cyclase C (GC-C), a receptor expressed on the apical membrane of intestinal mucosal cells, is activated by heat-stable enterotoxin (STa) produced by enterotoxigenic Escherichia coli, as well as the endogenous ligands guanylin and uroguanylin. In this study, novel peptides that interact with GC-C were generated using the cDNA display method, and their binding affinity and biological activity were evaluated. While the linear peptide library did not yield peptides with sufficient affinity for GC-C, three cyclic peptides (GCC-P1, GCC-P2, and GCC-P3), each containing two cysteine residues within a 15-residue sequence, were obtained from a cyclic peptide library containing nine-residue random sequences. GC-P2 exhibited significant binding affinity in Biacore assays, although the affinity was lower than those reported for known ligands. Notably, GCC-P2 and GCC-P3 demonstrated enhanced cGMP activity when used in combination with linaclotide. However, the agonist activity of these peptides was minimal, indicating that further modifications may be necessary to develop them for clinical applications. This study successfully extracted consensus sequences of peptide motifs that bind to GC-C from a highly diverse nine-residue random sequence library, which provides fundamental insights for the discovery and optimization of novel GC-C ligands., (© 2024 European Peptide Society and John Wiley & Sons Ltd.)

Cancer cachexia, characterized by the progressive loss of skeletal muscle mass, leads to functional impairment and poor prognosis. Anamorelin is approved for treating cancer cachexia in Japan; however, the factors influencing its discontinuation and the impact of combining anamorelin with rehabilitation remain unclear. Therefore, we retrospectively analyzed 82 patients with cancer cachexia to identify factors associated with anamorelin discontinuation and assess changes in nutritional status and motor function using non-dominant handgrip strength after 12 wk. Patients received outpatient rehabilitation, combining resistance and aerobic training every two weeks, alongside anamorelin therapy. Our findings indicate that patients with an ECOG performance status of 1 or 2 were less likely to continue anamorelin therapy for 12 wk compared to those with a performance status of 0 (odds ratio 2.71; 95% CI 1.05 - 7.00; p  = 0.040). Significant improvements were observed in body weight (48.8 to 53.7 kg, p  < 0.001), skeletal muscle mass (6.4 to 6.9 kg/m 2 , p  < 0.001), FAACT score (11.5 to 18.0, p  < 0.001), and non-dominant handgrip strength (20.5 to 21.7 kg, p  = 0.018) after 12 wk. Early initiation of anamorelin with regular rehabilitation is recommended to enhance nutritional status and motor function in patients with cancer cachexia.

Purpose: Laparoscopic cholecystectomy for a benign disease is often the initial endoscopic surgery performed by trainee surgeons. However, a lack of surgical experience is associated with prolonged operative times, which may increase the risk of postoperative complications and poor outcomes. This study aimed to identify the factors associated with prolonged operative times for laparoscopic cholecystectomy performed by inexperienced surgeons., Methods: This retrospective single-center study was conducted between January 2018 and December 2023. We performed a multivariate analysis to identify the factors associated with prolonged operative time by analyzing elective cases of laparoscopic cholecystectomy performed by surgeons with limited experience., Results: The study included 323 patients, subjected to a median operative time of 89 min. Multivariate analysis identified that patient characteristics such as male sex, increased body mass index, and a history of conservative treatment for cholecystitis, as well as operating surgeon's post-graduation years (< 4 years), and an attending surgeon without endoscopic surgical skill certification from the Japan Society of Endoscopic Surgery, were independent risk factors for a prolonged operative time., Conclusion: Our findings suggest that endoscopic surgical skill-certified attending surgeons have excellent coaching skills and mitigate the operative time for elective cholecystectomy., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Cardiac tamponade is a rare postoperative complication of esophagectomy, with no previous reports of association with coronary artery aneurysm rupture. We present a case of cardiac tamponade caused by coronary aneurysm rupture following esophageal cancer surgery. A 68-year-old man with no history of heart disease underwent robotic subtotal esophagectomy for esophageal squamous cell carcinoma. He experienced intermittent chest pain on postoperative day (POD) 17. Echocardiography revealed increasing pericardial fluid, and pericardiocentesis on POD 34 revealed bloody pericardial fluid. Contrast-enhanced computed tomography and coronary angiography revealed a ruptured coronary aneurysm causing cardiac tamponade. Emergency surgery with a median sternotomy achieved hemostasis, and the patient recovered successfully. Cardiac tamponade after esophageal surgery, particularly from coronary aneurysm rupture, is rare. Prompt diagnosis and treatment are crucial for patient survival. Despite its risks, median sternotomy was effective in achieving rapid hemostasis and patient recovery in this case., Competing Interests: The authors declare that they have no competing interests., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background: An enterocutaneous fistula (ECF) is defined as an abnormal communication between the gastrointestinal tract and skin. ECFs are rarely encountered in clinical practice, yet are frequently difficult to treat. Few reports exist regarding the surgical techniques for the treatment of an ECF. Therefore, we report a case of refractory ECF with concomitant severe adhesions, in which we performed combined laparoscopic adhesiolysis and planned open conversion., Case Presentation: A 57-year-old female patient underwent a laparotomy for an ovarian cyst in her 20s. At 46 years, adhesiolysis without bowel resection was performed for adhesive small bowel obstruction (SBO). However, her symptoms did not improve. Eighteen days postoperatively, she underwent a reoperation and jejunostomy. An ECF developed post-reoperation; therefore, stoma closure and radical surgery for the ECF were planned. Due to the severe adhesions, only stoma closure was performed, based on intraoperative assessments. The patient was subsequently referred to our hospital. First, skin care around the fistula was provided during an outpatient visit. Appropriate sizing of the stoma pouch was performed, to improve erosions and ulcers. Thereafter, debridement of the perifistula skin and simple closure of the ECF outlet were attempted; however, the ECF recurred shortly thereafter. After 8 years of regular skin care, with the ECF remaining stable, however, manifesting as symptomatic SBO, she underwent laparoscopic adhesiolysis. This procedure was initiated in the epigastric region, where relatively fewer adhesions were anticipated. Post-open conversion, partial resection of the small intestine at four locations, including the fistula site, was performed. Postoperatively, jejunal edema and peristaltic dysfunction, due to narrowing of the superior mesenteric artery occurred. Regular drainage by percutaneous endoscopic gastrostomy was required. However, she improved and was discharged 3 months post-operatively. Three years post-operatively, the ECF and SBO did not recur., Conclusions: We reported a case of refractory ECF in which we were able to safely perform surgery, by combining laparoscopic adhesiolysis and a planned open conversion. Therefore, the surgical approach used in this case may be an option for securing a safe surgical field, while avoiding collateral damage., (© 2024. The Author(s).)

We report a case of a Morgagni hernia repaired by primary closure with an extra-abdominal suture. Moreover, we reviewed cases of laparoscopically repaired Morgagni hernia, in which the size of the hernia defect was known, to establish a size criterion for mesh utilization. An 87-year-old woman presented to our hospital with right upper abdominal pain and vomiting. She had no history of abdominal surgery or trauma. Chest radiography and computed tomography (CT) revealed a Morgagni hernia, with the stomach and transverse colon herniated into the right chest cavity. Initially, an endoscopic repair was performed for the herniated stomach due to her age, which was successful. However, she had a recurrence 2 days later, prompting us to perform a semi-emergent laparoscopic surgery. Laparoscopic examination revealed a Morgagni defect, with the omentum, transverse colon, and stomach herniated, with the stomach reduced by pneumoperitoneum. Fortunately, the herniated organs could be easily relocated into the abdomen with no adhesions. The hernia defect measured 6 x 3 cm. We performed primary closure with an extra-abdominal suture. No sac resection was performed. The operation lasted 98 min. Oral intake was initiated on postoperative day 1, and the patient was discharged on postoperative day 3 without complications. Chest radiography and CT scans at 1 month postoperatively showed no recurrence, and the patient remained asymptomatic at the 9-month follow-up examination. According to our review findings, primary closure is an efficient method for small hernia defects (rule of thumb: width, <4 cm; length, <7 cm)., Competing Interests: The authors declare no competing interests., (Copyright: Makoto Hasegawa et al.)

Coenzyme Q10 (CoQ10) is essential for mitochondrial ATP production and functions as an important antioxidant in every biomembrane and lipoprotein. Due to its hydrophobicity, a binding and transfer protein for CoQ10 is plausible, and we previously described saposin B as a CoQ10-binding and transfer protein. Here, we report that prosaposin, the precursor of saposin B, also binds CoQ10. As prosaposin is both a secretory protein and integral membrane protein, it is ubiquitous in the body. Prosaposin was isolated from human seminal plasma, and CoQ10 was extracted from hexane solution into the water phase. It was additionally found that immunoprecipitates of mouse brain cytosol generated using two different anti-prosaposin antibodies contained coenzyme Q9. Furthermore, mouse liver cytosol and mouse kidney cytosol also contained prosaposin-coenzyme Q9 complex. These results suggest that prosaposin binds CoQ10 in human cells and body fluids. The significance and role of the Psap-CoQ10 complex in vivo is also discussed., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2024 JCBN.)

Objectives: Multidrug-resistant (MDR) bacterial infections are highly prevalent among long-term care facility (LTCF) residents, and are thus important targets for antimicrobial stewardship. Diagnoses of urinary tract infections (UTIs), which are associated with antimicrobial use in these facilities, are not always made by physicians. Past epidemiologic studies have included asymptomatic bacteriuria together with UTIs. The National Healthcare Safety Network has initiated a surveillance program to identify the causative organisms of UTIs in LTCF residents. In Japan, medical care for these residents is provided through in-person physician visits; however, limited related data are available. Therefore, we investigated the organisms causing UTIs and their drug susceptibility among LTCF residents in central Japan, and examined the prevalence of multidrug resistance, its risk factors, and correlations with clinical outcomes., Methods: We retrospectively evaluated clinical and urine culture data of LTCF residents with physician-diagnosed UTIs between April 1, 2019, and April 30, 2022., Results: The detection rate of multidrug-resistant organisms was high, with Escherichia coli being the most prevalent. Ceftriaxone was frequently used for initial therapy. The initial antimicrobial agents were significantly less active against MDR pathogens than non-MDR pathogens. Most residents continued to receive the initial agents regardless of culture results. Nonetheless, differences in the therapy duration, relapse and hospitalization rates, and death rate within 28 days between the multidrug-resistant and non-multidrug-resistant groups were not significant., Conclusions: Antimicrobial stewardship is essential for reducing antimicrobial use and selective pressure in LTCFs in Japan; however, more specific data are needed for its effective implementation.

Introduction: Geriatric Nutritional Risk Index (GNRI) is a reliable index derived from serum albumin levels, height, and weight. Although various prognostic factors have been studied, the effect of preoperative nutritional status on surgical outcomes remains unexplored. This study aimed to evaluate the efficacy of the GNRI in predicting postoperative outcomes of lower gastrointestinal perforation., Methods: Eighty patients treated at our institution between January 2016 and December 2022 were retrospectively analyzed. This study primarily focused on the correlation between preoperative GNRI and two key outcomes: postoperative hospital stay duration and 1-year mortality rate., Results: Our findings revealed a significant association between low GNRI scores and increased 1-year mortality (odd ratio 4.0, 95% confidence interval [CI] 1.1-16, p = 0.025). Kaplan-Meier analysis and log-rank test showed that patients in the low GNRI group had markedly poorer overall survival rates than those in the high GNRI group (12-month survival rate 0.88 [95% CI: 0.75-0.95] vs. 0.65 [95% CI: 0.47-0.78]; p = 0.018). Additionally, both univariate and multivariate analyses indicated that lower GNRI scores were associated with prolonged hospital stays., Conclusion: We showed that a low GNRI score was associated with high mortality and prolonged hospital stay after emergency surgery for lower gastrointestinal perforation., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Although the 20S core particle (CP) of the proteasome is an important component of the 26S holoenzyme, the stand-alone 20S CP acts directly on intrinsically disordered and oxidized/damaged proteins to degrade them in a ubiquitin-independent manner. It has been postulated that some structural features of substrate proteins are recognized by the 20S CP to promote substrate uptake, but the mechanism of substrate recognition has not been fully elucidated. In this study, we screened peptides that bind to the 20S CP from a random eight-residue pool of amino acid sequences using complementary DNA display an in vitro molecular evolution technique. The identified 20S CP-binding amino acid sequence was chemically synthesized and its effects on the 20S CP were investigated. The 20S CP-binding peptide stimulated the proteolytic activity of the inactive form of 20S CP. The peptide bound directly to one of the α-subunits, opening a gate for substrate entry on the α-ring. Furthermore, the attachment of this peptide sequence to α-synuclein enhanced its degradation by the 20S CP in vitro. In addition to these results, docking simulations indicated that this peptide binds to the top surface of the α-ring. These peptides could function as a key to control the opening of the α-ring gate.

Background: Activity levels of patients often scaled as performance status (PS) is the most important scale in oncology populations for treatment decisions and prognosis prediction. However, it is usually subjective and open to bias. The need for more objective and reliable assessment tools is mandatory for safe and effective oncology practice. To investigate the reliability of continuous vital and activity evaluation monitored by bed sensor systems in advanced cancer patients, we conducted a cohort pilot study in hospitalized cancer patients under several PS conditions., Methods: Adult patients, either admitted in the oncology department or palliative care unit, were enrolled in the study after written informed consent. Continuous monitoring for 48 hours from the first night of admission was performed without any restrictions on the patients. Calculated acceleration of movement [activity index (ACI)], % time on bed and number of bed leave in an 8-hour period, as well as other vital signs were monitored. Analysis focused on change of PS to 3, a standard cut-off for curative cancer treatment and PS4, vital for prognosis assessment., Results: Nineteen patients' data were analyzed. In PS4 palliative care patients, ACI was significantly low and % time on bed was high from PS3 palliative care patients. Instabilities of respiratory rate, respiratory tidal weight and heart rate were significantly higher in palliative care patients (PS3, PS4) compared with oncology patients (PS1, PS2)., Conclusions: This result, though in need of larger trials, shows possibilities for continuous objective monitoring of patients in bed for PS assessment in advanced cancer patients.

We report a case of a 73-year-old man who underwent endoscopic mucosal resection (EMR) for early rectal cancer(i ntramucosal cancer)at other hospital 17 years ago. Ten years later, he underwent a total colonoscopy, which showed no recurrence of the tumor. Twelve years later, a mass with calcification was incidentally detected in front of the sacrum, which was diagnosed as a benign tumor at that time. Seventeen years later, he presented with constipation and diarrhea, and was detected of a sub-circumferential tumor in the rectum by a total colonoscopy. Biopsy revealed that the tumor was malignancy. CT showed a mass in the left lateral liver lobe. The mass was suspected of metastasis. Laparoscopic super lower anterior resection was performed for rectal cancer, and pathological examination showed that the tumor was pT4a, N3, M1(H), Stage Ⅳa. One month after surgery, laparoscopic hepatectomy was performed for liver metastasis. Six months after surgery, CT showed multiple lung metastases. He continues to undergo chemotherapy. Although this case was treated with EMR for intramucosal carcinoma, clinical history and pathological findings suggested local recurrence.

We report a case of laparoscopic sigmoid colon resection for sigmoid colon cancer after cystectomy for bladder cancer and ileal conduit surgery for urinary tract reconstruction. The patient was a male in his 70s. The patient presented to the Department of Gastroenterology with the complaint of nausea and loss of appetite, and findings that were suspicious of intestinal obstruction. The diagnosis was obstructive sigmoid colon cancer. The patient had a history of bladder cancer and had undergone cystectomy and ileal conduit surgery. Intraoperatively, we considered placing a ureteral stent to identify the left ureter through the dorsal mesentery of the sigmoid colon, but we decided that stent placement would be difficult because of a history of conduit stenosis during a previous close examination of a patient with pyelonephritis. On the 21st day, a laparoscopic- assisted sigmoid colon resection was performed. The surgery was completed without any problems such as intraoperative ureteral injury. The patient was discharged home on the 23rd postoperative day. Ten months after the surgery, the patient is alive without recurrence.

Background: The low acceptance rate of continuous positive airway pressure therapy in postoperative patients with untreated obstructive sleep apnea (OSA) indicates the necessity for development of an alternative postoperative airway management strategy. The authors considered whether the combination of high-flow nasal cannula and upper-body elevation could improve postoperative OSA., Methods: This nonblinded randomized crossover study performed at a single university hospital investigated the effect on a modified apnea hypopnea index, based exclusively on the airflow signal without arterial oxygen saturation criteria (flow-based apnea hypopnea index, primary outcome), of high-flow nasal cannula (20 l · min-1 with 40% oxygen concentration) with and without upper-body elevation in patients with moderate to severe OSA. Preoperative sleep studies were performed at home (control, no head-of-bed elevation) and in hospital (30-degree head-of-bed elevation). On the first and second postoperative nights, high-flow nasal cannula was applied with or without 30-degree head-of-bed elevation, assigned in random order to 23 eligible participants., Results: Twenty-two of the 23 (96%) accepted high-flow nasal cannula. Four participants resigned from the study. Control flow-based apnea hypopnea index (mean ± SD, 60 ± 12 events · h-1; n = 19) was reduced by 15 (95% CI, 6 to 30) events · h-1 with head-of-bed elevation alone (P = 0.002), 10.9 (95% CI, 1 to 21) events · h-1 with high-flow nasal cannula alone (P = 0.028), and 23 (95% CI, 13 to 32) events · h-1 with combined head-of-bed elevation and high-flow nasal cannula (P < 0.001). Compared to sole high-flow nasal cannula, additional intervention with head-of-bed elevation significantly decreased flow-based apnea hypopnea index by 12 events · h-1 (95% CI, 2 to 21; P = 0.022). High-flow nasal cannula, alone or in combination with head-of-bed elevation, also improved overnight oxygenation. No harmful events were observed., Conclusions: The combination of high-flow nasal cannula and upper-body elevation reduced OSA severity and nocturnal hypoxemia, suggesting a role for it as an alternate postoperative airway management strategy., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Overexpression of human dynactin-associated protein (dynAP) transforms NIH3T3 cells. DynAP is a single-pass transmembrane protein with a carboxy-terminal region (amino acids 135-210) exposed to the outside of the cell possessing one potential N-glycosylation site (position 143) and a distal C-terminal region (residues 173-210) harboring a Thr/Ser-rich (T/S) cluster that may be O-glycosylated. In SDS-PAGE, dynAP migrates anomalously at ~ 45 kDa, much larger than expected (22.5 kDa) based on the amino acid composition. Using dynAP mutants, we herein showed that the T/S cluster region is responsible for the anomalous migration. The T/S cluster region is required for transport to the cytoplasmic membrane and cell transformation. We produced and purified the extracellular fragment (dynAP135-210) in secreted form and analyzed the attached glycans. Asn143 displayed complex-type glycosylation, suggesting that oligosaccharide transferase may recognize the NXT/S sequon in the secretory form, but not clearly in full-length dynAP. Core I-type O-glycosylation (Gal-GalNAc) was observed, but the mass spectrometry signal was weak, clearly indicating that further studies are needed to elucidate modifications in this region., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study was to test whether or not the threshold to the detection of passive motion (TTDPM) and passive joint position sense on the affected shoulder of patients with rotator cuff tear (RCT) was impaired compared to those on the unaffected side and to investigate the relationship between the tear size and changes in the TTDPM and passive joint position sense induced by RCT. This study included 21 patients with unilateral RCT before arthroscopic rotator cuff repair. To investigate proprioception in this study, we measured the TTDPM and passive joint position sense in abduction and external rotation using an isokinetic dynamometer. The tear size was evaluated intraoperatively under direct arthroscopic visualization. The TTDPM in abduction and external rotation was significantly longer on the affected side than on the unaffected side. However, the angular absolute error in passive joint position sense in abduction and external rotation was not significantly different between the limbs. A comparison according to the tear size impaired proprioception of the TTDPM in the larger tear group showed significantly longer values than in the smaller group. There was impaired proprioception of TTDPM in patients with RCT, and the impaired proprioception was related to tear severity. Impaired proprioception of TTDPM may inhibit consistent muscle recruitment to achieve precise control. Our results suggest that clinicians should consider proprioceptive exercises for impaired proprioception in their treatment for conservative or postoperative patients., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) can cause a wide variety of infections, ranging from skin and soft tissue infections to life-threatening invasive diseases such as necrotizing pneumonia and infective endocarditis. Here, we present a case of a healthy young female presenting with fever, headache and nausea, who was diagnosed with mitral valve infective endocarditis due to CA-MRSA and whose course was complicated by meningitis and multiple septic emboli. The causative MRSA strain belonged to sequence type 97 and harbored SCCmec Ⅳc but not lukS/F-PV genes. ST97, which is frequently isolated from livestock animals and known as a common lineage of livestock-associated MRSA, may cause invasive infection in the community., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Metal mesh devices (MMDs) are novel materials that enable the precise separation of particles by size. Structurally, MMDs consist of a periodic arrangement of square apertures of characteristic shapes and sizes on a thin nickel membrane. The present study describes the separation of aerosol particles using palm-top-size collection devices equipped with three types of MMDs differing in pore size. Aerosols were collected at a farm located in the suburbs of Nairobi, Kenya; aerosol particles were isolated, and pathogenic bacteria were identified in this microflora by next-generation sequencing analysis. The composition of the microflora in aerosol particles was found to depend on particle size. Gene fragments were obtained from the collected aerosols by PCR using primers specific for the genus Mycobacterium . This analysis showed that Mycobacterium obuense , a non-tuberculous species of mycobacteria that causes lung diseases, was present in these aerosols. These findings showed that application of this MMD analytical protocol to aerosol particles can facilitate the investigation of airborne pathogenic bacteria.

Background: Generally, studies of gadolinium (Gd) deposition in humans measure concentration by analyzing formalin fixed postmortem tissue. However, the effect of formalin fixation on measured Gd concentration has not been well investigated., Purpose: To evaluate the effect of fixation by comparing Gd concentration in fresh versus formalin-fixed postmortem human tissues., Material and Methods: Fresh samples of bone and skin were collected from autopsy cases with previous exposure to Gd-based contrast agents (GBCAs). The type of GBCA administered, dose, and estimated glomerular filtration rate were recorded. Each tissue sample was cut into three aliquots. Paired samples were stored fresh frozen while the remaining two were stored in 10% neutral buffered formalin for one and three months, respectively. Gd concentration was measured using ICP-MS., Results: Of 18 autopsy cases studied, 12 were exposed to only macrocyclic GBCA, one to only linear agents, and five received both macrocyclic and linear agents. On average, Gd concentration for bone decreased 30.7% after one month of fixation ( P  = 0.043) compared to non-fixed values. There was minimal, if any, change in concentration between one and three months (average decrease 1.5%; P  = 0.89). The findings were numerically similar for skin tissue with an average decrease of 36.9% after one month ( P  = 0.11) and 6.0% ( P  = 0.73) between one and three months., Conclusion: Formalin fixation appears to decrease Gd concentration in bone and skin by approximately 30%-40% on average. The largest decrease occurs within the first 30 days of fixation followed by a considerably smaller decrease at 60 days.

Background: Rapid emergence from general anaesthesia is desirable only if safety is not sacrificed. Mechanical hyperventilation during hypercapnia produced by carbon dioxide infusion into the inspired gas mixture or by rebreathing was reported to shorten emergence time from inhalation anaesthesia., Objectives: To test the hypothesis that hypercapnia produced by hypoventilation before desflurane cessation shortens emergence time from general anaesthesia (primary hypothesis) and reduces undesirable cardiorespiratory events., Design: A single-blinded randomised controlled study., Setting: A single university hospital., Patients: Fifty adult patients undergoing elective abdominal surgery under general anaesthesia using desflurane inhalation and intra-operative epidural anaesthesia., Intervention: The patients were randomly assigned to either the normocapnia or hypercapnia group., Main Outcome Measures: Emergence time from desflurane anaesthesia and comparison of the incidence of 11 predefined undesirable cardiorespiratory events during and after emergence from anaesthesia between the groups., Results: Forty-six patients were included in the analysis. End-tidal carbon dioxide concentrations at cessation of desflurane were 35 ± 6 mmHg (mean ± SD) and 52 ± 6 mmHg in normocapnia (n = 23) and hypercapnia groups (n = 23), respectively. Emergence time was significantly faster in the hypercapnia group than the normocapnia group: 9.4 ± 2.4 min, hypercapnia: 5.5 ± 2.6 min, (P < 0.001) with a difference of 3.8 min on average (95% CI: 2.4 to 5.3). Spontaneous breathing established before recovery of consciousness was more evident in hypercapnia patients (normocapnia: 13%, hypercapnia: 96%, P < 0.001). Hypercapnia patients had more episodes of bradypnoea and apnoea before emergence of consciousness. In contrast, after tracheal extubation, incidences of bradypnoea and hypopnoea were more common in the normocapnia group. Undesirable cardiovascular events were not common, and no group differences were observed during emergence and postextubation periods., Conclusion: Hypoventilation-induced hypercapnia before desflurane cessation shortens the emergence time without causing additional clinically significant undesirable events., Trial Registration: UMIN Clinical Trials Registry (UMIN000020143) https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000023266&language=E., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

The use of a metal mesh device (MMD) as a precision bacterial separation filter is described. The MMD uses a structure in which identically shaped pores are arranged in a thin metal membrane. Four types of MMD with different pore sizes were used to fractionate bacteria in two types of soil. Through metagenomic analysis, the distribution of bacteria in the soil samples and in each MMD fraction was examined. In addition, eight types of previously described organic compound-degrading bacteria were used to evaluate the method, and changes in their composition following MMD fractionation were investigated. It was found that MMD fractions were enriched for all eight bacteria when compared with the initial sample. These results suggest that bacterial fractionation using MMD can enrich bacteria occurring at low frequencies in environmental samples.

Background Linear gadolinium-based contrast agents (GBCAs) are known to be retained at higher levels of gadolinium than macro-cyclic GBCAs. However, very little is known regarding their relative elimination rates and retained fraction of injected gadolinium. Purpose To quantify and compare gadolinium retention and elimination rates in human brain tissue, skin, and bone obtained from cadavers exposed to single-agent administration of either gadoteridol (macrocyclic GBCA) or gadobenate dimeglumine (linear GBCA). Materials and Methods Autopsy cases from August 2014 to July 2019 of patients exposed to a single type of GBCA, either gadoteridol or gadobenate dimeglumine, either single or multiple doses, were included. Gadolinium levels in the brain, skin, and bone were analyzed with inductively coupled plasma mass spectrometry. Linear regression was used to compare gadolinium retention between agents and estimate elimination rates of the retained gadolinium using the time between last injection and death. Results Twenty-eight cadavers with gadoteridol exposure and nine with gadobenate dimeglumine exposure were identified (22 men; age range, 19-83 years). The median gadolinium retention of gadobenate dimeglumine was 3.0-6.5 times higher than that of gadoteridol in the brain ( P < .02), 4.4 times higher in bone ( P = .002), and 2.9 times higher in skin ( P = .05). Gadolinium retention in the globus pallidus (GP), dentate nucleus (DN), white matter (WM), bone, and skin decreased with time elapsed from last administration to death in both the gadobenate dimeglumine (GP: -3% per twofold increase in time, P = .69; DN: -2%, P = .83; WM: -20%, P = .01; bone: -22%, P = .07; skin: -47%, P < .001) and gadoteridol (GP: -17%, P = .11; DN: -16%, P = .15; WM: -30%, P < .001; bone: -11%, P = .16; skin: -24%, P = .01) groups ( P values for elimination are compared with a null hypothesis of no elimination). Conclusion The linear agent gadobenate dimeglumine retains several-fold higher levels of gadolinium in the brain and bone compared with the macrocyclic agent gadoteridol. Nonzero elimination of retained gadolinium was detected in the white matter and skin for both agents. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Overexpression of human dynactin-associated protein isoform a (dynAPa) transforms NIH3T3 cells. DynAPa is a single-pass transmembrane protein with a carboxy-terminal region exposed to the outside of cells. According to the NCBI RefSeq database, there may be two other splicing variants of the encoding gene (dynAPb and c). DynAPa and c differ in some amino-terminal residues (NH 2 -MVA in dynAPa and NH 2 -MEYQLL in dynAPc). DynAPb has the same amino-terminal residues as dynAPc, but lacks 55 residues in the intracellular region. All three isoforms have the same carboxy-terminal region, including the transmembrane domain. Expression of mRNAs of three splicing variants was found in human cancer cell lines ACHN and Caki-1. The subcellular localization and in vitro cell transformation ability of the three isoforms were examined using NIH3T3 cells overexpressing each respective isoform. All isoforms were found to be localized to the Golgi apparatus and plasma membrane, where the carboxy-terminal region was exposed to the outside of cells. Cell transformation was tested using focus formation due to loss of contact inhibition of cell proliferation, and colony formation was examined on soft agar and spheroid formation in ultralow U-bottomed wells. DynAPa robustly formed foci and colonies on soft agar and spheroid, whereas these abilities were considerably decreased for dynAPb and completely lost in dynAPc. These findings warrant dissection studies to identify the dynAP domain that is required for cell transformation., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Nocturnal periodic breathing of chronic opioid users has been predominantly documented by the use of polysomnography. No previous studies have assessed the opioid effects of respiratory rhythms throughout the day without the use of physical restraint. We recently developed a contact-free unconstraint vital sign monitoring system with four load cells placed under the bed legs, which allows continuous measurements of respiratory change at the center of gravity on the bed. We aimed to reveal details of the patient's 24-h respiratory status under a monitoring system and to test the hypothesis that respiratory rhythm abnormalities are opioid dose-dependent and worsen during the night time. Continuous 48-h respiratory measurements were successfully performed in 51 patients with advanced cancer (12 opioid-free patients and 39 opioid-receiving patients). Medians of respiratory variables with minimal body movement artifacts were calculated for each 8-h split time period. Compared with opioid-free patients, opioid-receiving patients had slower respiratory rate with higher respiratory rate irregularity without changing tidal centroid shift regardless of the time period. Irregular ataxic breathing was only identified in opioid-receiving patients (33%, P = 0.023) whereas incidence rate of periodic breathing did not differ between the groups. Multivariate regression analyses revealed that opioid dose was an independent risk factor for occurrence of irregular breathing [odds ratio 1.81 (95% CI: 1.39-2.36), P < 0.001], and ataxic breathing [odds ratio 2.08 (95% CI: 1.60-2.71), P < 0.001]. Females developed the ataxic breathing at lower opioid dose compared with males. We conclude that respiratory rhythm irregularity is a predominant specific feature of opioid dose-dependent respiratory depression particularly in female patients with advanced cancer. NEW & NOTEWORTHY Through usage of a novel contact-free unconstraint vital sign monitoring system with four load cells placed under the bed legs allowing continuous measurements of respiratory changes of center of gravity on the bed, this study is the first to assess detailed respiratory characteristics throughout day and night periods without interference of daily activities in patients with advanced cancer receiving opioids. Respiratory rhythm irregularity is a predominant specific feature of opioid dose-dependent respiratory depression particularly in female patients with advanced cancer.

This study utilized laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to quantify gadolinium in the hair of autopsy cases that had received gadolinium-based contrast agents (GBCAs) before death. Consecutive autopsy cases were reviewed for GBCA injections and subjects who received a single type of GBCA in the year before death were included. Hair samples were analyzed using LA-ICP-MS as a line scan technique and parameters were optimized to maximize instrument sensitivity, accuracy, and precision. Linear regression analyses between hair measures and gadolinium dose were executed. LA-ICP-MS analysis produced a time-resolved record of GCBA exposure, with the position of the gadolinium peak maxima along the hair shaft providing a good estimate for the day that GBCA injection occurred (R 2  = 0.46; p = 0.0022); however, substantial within and between subject variation in the position of the GBCA peak was observed. Average area under the curve for gadolinium peaks in the hair samples was a better predictor of gadolinium dose (R 2  = 0.41; p = 0.0046), compared to the average of peak maxima concentration. Correlation between area under the curve and dose suggests that LA-ICP-MS analysis of hair may be an effective method to evaluate gadolinium levels in subjects in vivo after exposure to GBCAs. This study demonstrates that analysis of human hair using techniques with high spatial resolution such as LA-ICP-MS has excellent potential to reveal time-dependent signatures of past exposures.

Here, we report a case of ascending colon cancer successfully treated with laparoscopic right hemicolectomy in a 74- year-old man with a medical history of hemophilia A. He was admitted to our hospital because of bloody stool and diagnosed with type 2 ascending colon cancer based on colonoscopy findings. Preoperatively, blood transfusion and administration of recombinant factor Ⅷ products were performed. Surgery involved laparoscopic right hemicolectomy plus group 3 lymph node dissection. No complications, such as bleeding, occurred during hospitalization. The patient was discharged on postoperative day 8. There have been a few reports of laparoscopic surgery for patients with hemophilia. However, this case suggests that it can be safely performed with planned factor Ⅷ supplementation in the perioperative period.

Objectives: We used laser ablation inductively coupled plasma mass spectrometry to quantify gadolinium in hair samples from autopsy cases with gadolinium-based contrast agent (GBCA) exposure. Hair gadolinium data were correlated with gadolinium concentrations in brain, skin, and bone tissues from the same case to investigate a potential noninvasive method for gadolinium quantification and monitoring., Materials and Methods: Medical records from autopsy cases at our institution were screened for history of GBCA exposure. Cases with exposure to a single type of GBCA with the most recent injection occurring within 1 year were identified and included in the study. The concentration of gadolinium in hair samples was analyzed by laser ablation inductively coupled plasma mass spectrometry, and brain (globus pallidus, dentate nucleus, white matter), bone, and skin tissues were analyzed by bulk inductively coupled plasma mass spectrometry. The mean of the maximum value in the hair samples was used to generate a representative measurement of the hair gadolinium concentration for each case. A linear regression analysis between each tissue type and hair was conducted to assess for possible correlation., Results: Tissue and hair samples from 18 autopsies (16 cases with exposure to GBCA, 2 controls) were included in the study. Comparing the different tissues revealed good correlation between some tissue types. The best model fit occurred between white matter and hair (R = 0.83; P < 0.0001) followed by the comparison between dentate nucleus and hair (R = 0.72; P < 0.0001) and dentate nucleus and skin (R = 0.70; P < 0.0001)., Conclusions: A significant correlation in this study between hair gadolinium concentrations and brain and skin gadolinium concentrations suggests that hair may serve as a safe and effective biomonitoring tissue for patients who receive GBCA injections.

As technology has improved in recent years, it has become possible to create new valuable functions by combining various devices and sensors in a network. This concept is referred to as the Internet of Things (IoT), and predictive maintenance is a new valuable function associated with the IoT. In large-scale experimental facilities with many researchers, it is not desirable that experiments cannot be performed due to sudden failure of equipment. For this reason, it is important to predict the failure in advance based on the measurement results of sensors and to perform repairs in a planned manner. On the Q-shu University experiment with steady-state spherical tokamak (QUEST) large experimental device, it is necessary to drive a large current of 50 kA, and the diagnosis of its power line deterioration is well performed as predictive maintenance through the evaluation of its contact resistances of several micro ohms order on the network. In addition, as an example of the IoT, mechanisms to assist safe operation, such as a sound alarm system and an entrance management system, are built by sharing experimental information between devices via the network., (© 2020 The Author(s).)

Background: Repeat liver resection is an effective treatment approach for patients with recurrent hepatocellular cell carcinoma (HCC). However, the surgical feasibility and oncological significance of repeat laparoscopic liver resection (r-LLR) remain unproven. This study evaluates and compares the clinical outcomes of non-anatomic r-LLR applied towards recurrent HCC, with those of primary LLR (p-LLR) for primary HCC., Methods: This retrospective study reports 104 patients with HCC, treated with LLR between 2014 and 2018. Twenty eight of these patients underwent r-LLR for recurrent HCC. The clinical and surgical variables were reviewed for all cases., Results: The analysis was limited to non-anatomic resection across both groups (r-LLR: 89% (25/28) vs. p-LLR: 80% (61/76)). There were no statistically significant differences about patient background between the two groups, with the exception of Child-Pugh classification. r-LLR surgical techniques included single-site laparoscopic adhesiolysis (32%, 8/25), Pringle maneuver (8%, 2/25), and crush-clamp method using BiClamp for hepatic parenchymal transection (72%, 18/25). No severe postoperative complications were observed in the r-LLR group. Postoperative hospital stays and procedure-related postoperative survival were similar for both groups., Conclusions: Non-anatomical r-LLR renders comparable surgical and oncological outcomes. Our data suggest that non-anatomical r-LLR is a safe and feasible therapeutic approach to recurrent HCC.

Alcohol dehydrogenase (ADH) is important for preventing alcohol toxicity and developmental disorders, and may be involved in other diseases including neurodegenerative diseases. We found that the major acceptor protein of polyADP-ribosylation in a model organism of neurodegeneration using a Drosophila melanogaster mutant lacking poly(ADP-ribose) glycohydrolase, was ADH. Thus we postulated that human ADH activity might be regulated by polyADP-ribosylation, a post-translational modification. The radioactivity of [ 32 P]NAD + was incorporated into human ADH1 by human poly(ADP-ribose) polymerase 1 in vitro, but was not incorporated when heat-inactivated PARP1 or a PARP inhibitor, 3-aminobenzamide, was used. The incorporated radioactivity was not released from ADH1 protein in the presence of excess amount of ADP-ribose or poly(ADP-ribose) as competitors. However, it was released by incubation with 1 M neutral NH 2 OH or 0.1 N NaOH, but was not with 0.1 N HCl, suggesting the bond between ADH1 and poly(ADP-ribose) is an ester linkage. When HepG2 cells, a human hepatoma cell line, were cultured in the presence of another PARP inhibitor, olaparib, ADH activity of the cell was significantly increased. These results suggest that polyADP-ribosylation could regulate ADH activity in vivo and might be involved in neurodegeneration., (Copyright © 2019. Published by Elsevier Inc.)

KDM5 family members (A, B, C and D) that demethylate H3K4me3 have been shown to be involved in human cancers. Here we performed screening for KDM5A inhibitors from chemical libraries using the AlphaScreen method and identified a battery of screening hits that inhibited recombinant KDM5A. These compounds were further subjected to cell-based screening using a reporter gene that responded to KDM5A inhibition and 6 compounds were obtained as candidate inhibitors. When further confirmation of their inhibition activity on cellular KDM5A was made by immunostaining H3K4me3 in KDM5A-overexpressing cells, ryuvidine clearly repressed H3K4me3 demethylation. Ryuvidine prevented generation of gefitinib-tolerant human small-cell lung cancer PC9 cells and also inhibited the growth of the drug-tolerant cells at concentrations that did not affect the growth of parental PC9 cells. Ryuvidine inhibited not only KDM5A but also recombinant KDM5B and C; KDM5B was the most sensitive to the inhibitor. These results warrant that ryuvidine may serve as a lead compound for KDM5 targeted therapeutics.

Extra-adrenal paraganglioma is a rare form of neuroendocrine neoplasm capable of catecholamine secretion. The surgical risks associated with the tumor location are compounded in this case of a kyphotic patient. This report presents the successful application of laparoscopy on extra-adrenal paraganglioma located behind the Spiegel lobe in a kyphotic patient. The operation was performed after 1 week of α-blocker administration. The laparoscopic approach, with the patient in the left hemilateral decubitus position on a rotating table, provided optimal access for safe tumor resection after complete hepatic right lobe mobilization. The patient's postoperative course was uneventful. Based on the results, the laparoscopic approach can be a safe and effective method for resecting extra-adrenal paraganglioma in the challenging case of a kyphotic patient., (© 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Two types of metal mesh devices with hole diameters of 1.7 and 0.3 μm were prepared by an electroforming method. The metal mesh devices with hole diameters of 1.7 and 0.3 μm transmitted electromagnetic waves with frequencies of approximately 100 and 285 THz, respectively. These spectral frequencies shifted depending on the adsorption amount of protein. The slope in the linear relationship between the adsorption amount and spectral shift (i.e. sensitivity) of the metal mesh device with a hole diameter of 0.3 μm was seven times as great as that of the device with a hole diameter of 1.7 μm. These results agreed with the theoretical concept of the sensitivity for the metal mesh device sensor being proportional to the square of the transmittance frequency. As biosensors, the structurally refined metal mesh devices amplified the output signals.

After Fukushima disaster in 2011, the health status of the region's residents deteriorated. We analyzed the health status, care needs, and access to health services among evacuees and non-evacuees using healthcare expenditure (for self-employed and unemployed individuals aged < 75 years) and long-term care expenditure (mainly for individuals aged ≥ 65 years). Fukushima Prefecture was divided into four areas according to their evacuation status: non-EOAs (municipalities that did not include evacuation order areas (EOAs)); EOAs/non-EOAs (municipalities that included both EOAs and non-EOAs); short-term EOAs (municipalities where the EOA designation was lifted in most areas by fiscal year (FY) 2011); and long-term EOAs (municipalities where most EOA designations remained in place until the end of FY 2015). Increases in expenditure on healthcare and long-term care per capita in short-term and long-term EOAs were greater in FY 2015 than the average values in FYs 2008-2010. The increases in expenditure were higher in short-term and long-term EOAs than those in non-EOAs and EOAs/non-EOAs. The increases in dental health expenditure were attributed to enhanced accessibility to dental health facilities. Furthermore, the evacuations contributed to increases in healthcare and long-term care expenditure, independent of aging and improved accessibly to health facilities. Possible explanations for these increases include the poor health status of the evacuees following the evacuations, reduced availability of informal care provided by family members and neighbors, and reduced patient copayments. The findings highlight the necessity of health promotion among evacuees.

Oxidized low-density lipoprotein (ox-LDL) leads to atherosclerosis via lectin-like oxidized lipoprotein receptor-1 (LOX-1), one of the major receptor for ox-LDL. Inhibition of the binding of ox-LDL to LOX-1 decreases the proinflammatory and atherosclerotic events. The aim of the present study was to investigate whether protamine, a polybasic nuclear protein, interferes the binding of ox-LDL to LOX-1. Using sandwich ELISA with newly generated antibody, we measured the blocking effect of protamine on the binding of ox-LDL to LOX-1. Protamine dose-dependently inhibited the binding of ox-LDL to LOX-1. DiI-labeled ox-LDL uptake assay in two types of cultured human endothelial cells was performed with fluorescence microplate reader. Activation of extracellular-signal-regulated kinase (ERK)1/2 by ox-LDL was analyzed by immunoblotting. We found that protamine suppressed uptake of ox-LDL in endothelial cells and inhibited ERK1/2 activation by ox-LDL. These results suggest that protamine may possess anti-atherogenic potential by inhibiting ox-LDL binding to LOX-1 through electrostatic interactions.

Background: Anatomic variants of the biliary tree present challenges to surgical management during laparoscopic cholecystectomy and affect perioperative outcomes. An aberrant right hepatic duct connecting into the cystic duct is a practically important variation because of the susceptibility to serious postoperative refractory bile leakage. We report a successful case of laparoscopic cholecystectomy in the aberrant right hepatic duct of a patient diagnosed with chronic cystitis., Case Presentation: A 49-year-old man was referred to our department for treatment of chronic cholecystitis. Magnetic resonance cholangiopancreatography indicated that the cystic duct branched from the common bile duct and an aberrant bile duct connected to the cystic duct. Intraoperative cholangiography revealed that the bile duct was not confluent to the major right branch of the intrahepatic bile duct and drained a narrow area. Preoperative magnetic resonance cholangiopancreatography had diagnostic value. Furthermore, intraoperative cholangiography with the Critical View of Safety method was paramount to achieving safe cholecystectomy based on confirmation of the biliary anatomy and the drainage area of the aberrant right hepatic duct., Conclusion: We encountered a rare but clinically significant case of laparoscopic cholecystectomy. This case suggests that precise understanding of the anatomy and drainage area of the aberrant right hepatic duct preoperatively and intraoperatively can lead to safe cholecystectomy.

Rate of respiration is a fundamental vital sign. Accuracy and precision of respiratory rate measurements with contact-free load cell sensors under the bed legs were assessed by breath-by-breath comparison with the pneumotachography technique during two different dynamic breathing tasks in 16 awake human adults resting on the bed. The subject voluntarily increased and decreased the respiratory rate between 4 and 16 breaths/min ( n = 8) and 10 and 40 breaths/min ( n = 8) at every 2 breaths in 6 different lying postures such as supine, left lateral, right lateral, and 30, 45, and 60° sitting postures. Reciprocal phase changes of the upper and lower load cell signals accorded with the respiratory phases indicating respiratory-related shifts of the centroid along the long axis of the bed. Bland-Altman analyses revealed 0.66 and 1.59 breaths/min standard deviation differences between the techniques (limits of agreement: -1.22 to 1.36 and -2.96 to 3.30) and 0.07 and 0.17 breaths/min fixed bias differences (accuracy) (confidence interval: 0.04 to 0.10 and 0.12 to 0.22) for the mean respiratory rates of 10.5 ± 3.7 and 24.6 ± 8.9 breaths/min, respectively, regardless of the body postures on the bed. Proportional underestimation by this technique was evident for respiratory rates >40 breaths/min. Sample breath increase up to 10 breaths improved the precision from 1.59 to 0.26 breaths/min. Abnormally faster and slower respirations were accurately detected. We conclude that contact-free unconstraint respiratory rate measurements with load cells under the bed legs are accurate and may serve as a new clinical and investigational tool. NEW & NOTEWORTHY Four load cells placed under the bed legs successfully captured a centroid shift during respiration in human subjects lying on a bed. Breath-by-breath comparison of the breaths covering a wide respiratory rate range by pneumotachography confirmed reliability of the contact-free unconstraint respiratory rate measurements by small standard deviations and biases regardless of body postures. Abnormally faster and slower respirations were accurately detected. This technique should be an asset as a new clinical and investigational tool.

After the Great East Japan Earthquake and the subsequent Fukushima Daiichi Nuclear Power Station accident in 2011, there was a strong demand to promote disaster preparedness approaches and health checkups for the prevention of lifestyle diseases. This study examined the yearly change in the percentage of those who prepared for disasters and who utilized health checkups in Fukushima Prefecture, and identified the factors governing disaster preparedness and utilization of health checkups. We used the public opinion survey from 2011 to 2015 ( n = 677-779 each year) on prefectural policies that is conducted every year by the Fukushima Prefecture government Public Consultation Unit. We found that the percentage of those who prepare for disasters decreased, while that for health checkups did not significantly change. With regard to disaster preparedness, experiences of disaster enhance disaster preparedness, while bonds with other local people help to maintain preparedness. For health checkups, familiarity with the welfare service was the most important factor governing such consultations. The findings suggest that social capital should be promoted in order to improve disaster preparedness. The findings also suggest that residents' accessibility to medical and welfare services is also important in promoting the utilization of health checkups., Competing Interests: The authors declare no conflict of interest.

Ridaifen-F (RID-F) potently inhibits proteolytic activities of the 20S proteasome but poorly inhibits those of the 26S proteasome. Here, we report preparation of several conjugates in which various peptides are connected to RID-F. Conjugates with peptides consisting of seven amino acid residues significantly inhibited the 26S proteasome. Particularly, RID-F conjugated to an octaarginine peptide (R 8 , a so-called cell-penetrating peptide) inhibited intracellular proteasome activities and induced cell death in drug-resistant KMS-11 myeloma cells. RID-F conjugated to hydrophobic peptides also inhibited the 26S proteasome but failed to induce cell death, suggesting poor penetration into cells. We infer that the R 8 peptide has dual functions: (1) rapid penetration of conjugates into the cell increases intracellular drug concentrations sufficient for exhibition of its effect, and (2) recognition of the conjugates by the 26S proteasome stimulates drug entry into the catalytic chamber. In the presence of ATPγS, RID-F conjugates containing R 8 inhibited the 26S proteasome more potently than in the presence of ATP, suggesting efficient entry of drugs into the catalytic chamber in a similar fashion to the substrate. Taken together with docking simulations of RID-F conjugate interactions with proteasome active sites, the second function of R 8 peptide is plausible. Thus, the conjugation of nonpeptidic proteasome inhibitors to a cell-penetrating peptide could represent a viable strategy for overcoming the drug-resistance of tumor cells., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In this study, a sensitive fluorescence sensor was developed for the detection of small, fluorescence-labeled particles dispersed in a solution. The prototype system comprises of a laser confocal optical system and a mechanical sample stage to detect photon bursting of fluorescence-labeled small particles in sample volumes less than 5 μL within 3 minutes. To examine the feasibility of the prototype system as a diagnostic tool, assemblages of rotavirus and fluorescence-labeled antibody were analyzed. The detection sensitivity for rotavirus was 1 × 10 4 pfu/mL. Rotavirus in stool samples from patients with acute gastroenteritis was also detected. The advantages and disadvantages of this immunosensor with respect to ELISA and RT-PCR, the current gold standards for virus detection, are discussed.

Background: Depending on upper airway patency during anesthesia induction, tidal volume achieved by mask ventilation may vary. In 80 adult patients undergoing general anesthesia, the authors tested a hypothesis that tidal volume during mask ventilation is smaller in patients with sleep-disordered breathing priorly defined as apnea hypopnea index greater than 5 per hour., Methods: One-hand mask ventilation with a constant ventilator setting (pressure-controlled ventilation) was started 20 s after injection of rocuronium and maintained for 1 min during anesthesia induction. Mask ventilation efficiency was assessed by the breath number needed to initially exceed 5 ml/kg ideal body weight of expiratory tidal volume (primary outcome) and tidal volumes (secondary outcomes) during initial 15 breaths (UMIN000012494)., Results: Tidal volume progressively increased by more than 70% in 1 min and did not differ between sleep-disordered breathing (n = 42) and non-sleep-disordered breathing (n = 38) patients. In post hoc subgroup analyses, the primary outcome breath number (mean [95% CI], 5.7 [4.1 to 7.3] vs. 1.7 [0.2 to 3.2] breath; P = 0.001) and mean tidal volume (6.5 [4.6 to 8.3] vs. 9.6 [7.7 to 11.4] ml/kg ideal body weight; P = 0.032) were significantly smaller in 20 sleep-disordered breathing patients with higher apnea hypopnea index (median [25th to 75th percentile]: 21.7 [17.6 to 31] per hour) than in 20 non-sleep disordered breathing subjects with lower apnea hypopnea index (1.0 [0.3 to 1.5] per hour). Obesity and occurrence of expiratory flow limitation during one-hand mask ventilation independently explained the reduction of efficiency of mask ventilation, while the use of two hands effectively normalized inefficient mask ventilation during one-hand mask ventilation., Conclusions: One-hand mask ventilation is difficult in patients with obesity and severe sleep-disordered breathing particularly when expiratory flow limitation occurs during mask ventilation.

The virus reduction efficiency of each unit process is commonly determined based on the ratio of virus concentration in influent to that in effluent of a unit, but the virus concentration in wastewater has often fallen below the analytical quantification limit, which does not allow us to calculate the concentration ratio at each sampling event. In this study, left-censored datasets of norovirus (genogroup I and II), and adenovirus were used to calculate the virus reduction efficiency in unit processes of secondary biological treatment and chlorine disinfection. Virus concentration in influent, effluent from the secondary treatment, and chlorine-disinfected effluent of four municipal wastewater treatment plants were analyzed by a quantitative polymerase chain reaction (PCR) approach, and the probabilistic distributions of log reduction (LR) were estimated by a Bayesian estimation algorithm. The mean values of LR in the secondary treatment units ranged from 0.9 and 2.2, whereas those in the free chlorine disinfection units were from -0.1 and 0.5. The LR value in the secondary treatment was virus type and unit process dependent, which raised the importance for accumulating the data of virus LR values applicable to the multiple-barrier system, which is a global concept of microbial risk management in wastewater reclamation and reuse.

A 63-year-old woman visited our hospital complaining of abdominal pain and bloody discharge in November 2015. Abdominal CT revealed ileocecal intussusception. After hospitalization, a right colectomy was performed. Pathological diagnosis of the resected specimen was Mantle cell lymphoma. After this diagnosis, chemotherapy was initially administered. Following this, peripheral stem cell transplantation was carried out. We discovered this case of Mantle cell lymphoma by chance; therefore, here, we consider and introduce how this type of disease should be treated. We also introduce a rare case of Mantle cell lymphoma with intussusception at the cecum.

Immunoglobulin A (IgA) is the main antibody isotype secreted into the intestinal lumen. IgA plays a critical role in the defence against pathogens and in the maintenance of intestinal homeostasis. However, how secreted IgA regulates gut microbiota is not completely understood. In this study, we isolated monoclonal IgA antibodies from the small intestine of healthy mouse. As a candidate for an efficient gut microbiota modulator, we selected a W27 IgA, which binds to multiple bacteria, but not beneficial ones such as Lactobacillus casei. W27 could suppress the cell growth of Escherichia coli but not L. casei in vitro, indicating an ability to improve the intestinal environment. Indeed W27 oral treatment could modulate gut microbiota composition and have a therapeutic effect on both lymphoproliferative disease and colitis models in mice. Thus, W27 IgA oral treatment is a potential remedy for inflammatory bowel disease, acting through restoration of host-microbial symbiosis.

Directly acting antivirals recently have become available for the treatment of hepatitis C virus (HCV) infection, but there is no prophylactic vaccine for HCV. In the present study, we took advantage of the properties of Japanese encephalitis virus (JEV) to develop antigens for use in a HCV vaccine. Notably, the surface-exposed JEV envelope protein is tolerant of inserted foreign epitopes, permitting display of novel antigens. We identified 3 positions that permitted insertion of the HCV E2 neutralization epitope recognized by HCV1 antibody. JEV subviral particles (SVP) containing HCV-neutralization epitope (SVP-E2) were purified from culture supernatant by gel chromatography. Sera from mice immunized with SVP-E2 inhibited infection by JEV and by trans-complemented HCV particles (HCVtcp) derived from multi-genotypic viruses, whereas sera from mice immunized with synthetic E2 peptides did not show any neutralizing activity. Furthermore, sera from mice immunized with SVP-E2 neutralized HCVtcp with N415K escape mutation in E2. As with the SVP-E2 epitope-displaying particles, JEV SVPs with HCV E1 epitope also elicited neutralizing antibodies against HCV. Thus, this novel platform harboring foreign epitopes on the surface of the particle may facilitate the development of a bivalent vaccine against JEV and other pathogens.