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Introduction: This study aimed to investigate the survival rate, postoperative complications, and walking ability in cemented hemiarthroplasty (HA) for displaced femoral neck fractures according to the anaesthesia method., Methods: We conducted a retrospective study of a multicentre group (the TRON group). Three hundred fifty-eight patients who underwent cemented HA between 2015 and 2019 were selected; 289 patients of ≥75 years of age with no missing data were included. Patient background factors were matched and patients were assigned to spinal anaesthesia (SA) and general anaesthesia (GA) groups. The primary outcome was death at any time during the follow-up period. Secondary outcomes included postoperative complications and walking ability assessed using the Parker mobility score (PMS). Overall survival was evaluated using the Kaplan-Meier method, and differences were compared using the log-rank test. The incidence of each complication and PMS were compared between the two groups using Fisher's exact test., Results: Overall survival during follow-up was significantly higher in the SA group in comparison to the GA group (p = 0.037). In the SA and GA groups, the survival rate at 3 months postoperatively was 98.4% and 95.5%, respectively. The incidence of postoperative pneumonia was significantly higher in the GA (p = 0.012), and PMS at 3 months postoperatively was significantly higher in the SA group (p = 0.016)., Conclusion: The survival rate of elderly patients who underwent cemented HA was better in the SA group. General anaesthesia in cemented HA may be associated with lower life expectancy, increased incidence of pneumonia, and decreased walking ability., Competing Interests: Declaration of competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: In some cases, patients feel a perceived leg length discrepancy (P-LLD) despite no radiographic leg length discrepancy (R-LLD) after total hip arthroplasty (THA). We aimed to investigate the rate of postoperative P-LLD and the factors that cause postoperative P-LLD., Methods: A retrospective study was conducted on 100 patients with R-LLD ≤5 mm after THA. Patients were classified into two groups based on P-LLD post-THA: group P (with P-LLD) and group E (without P-LLD). Relevant data on the general characteristics and radiological findings between the two groups were compared., Results: We observed that 25 & 75% of patients belonged to group P and group E, respectively, with no significant difference in patient background. Postoperative Japanese Orthopedic Association (JOA) classification of pain and activities of daily living scores were significantly lower in group P than in group E (37.2 ± 3.9 vs. 39.1 ± 2.2, respectively; P = 0.013, and 16.2 ± 4.2 vs. 18.2 ± 2.2, respectively; P = 0.011). The preoperative pelvic oblique angle (POA) was significantly larger in group P than in group E (3.3 ± 2.3° vs. -0.2 ± 2.1°; respectively; P < 0.01). The pelvis tilted toward the surgical side was significantly higher in group P than in group E(88% vs 57%; respectively; P = 0.013). The preoperative C7 coronal vertical axis (C7 CVA) was significantly larger in group P than in group E (6.7 ± 14.7 mm vs. -0.2 ± 10.3 mm; respectively; P = 0.028). Multivariate logistic analysis revealed that preoperative POA (OR, 3.71; 95% CI: 1.86-8.12; P < 0.01) and the pelvis tilted toward the surgical side (OR, 4.14; 95% CI: 2.07-9.71; P = 0.022) were independent risk factors for P-LLD after THA., Conclusion: Even though there was no postoperative R-LLD, 25% of patients had P-LLD. A large preoperative POA and the pelvis tilted toward the surgical side were independent risk factors for P-LLD after THA., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Patients with locomotive syndrome (LS) are poor ambulatory status and a high risk of requiring nursing care. The purpose of this study is to investigate the relationship between LS and fall risk among community-dwelling elderly individuals., Methods: The subjects were Japanese elderly individuals aged 65 and over who participated in Yakumo study 2019 (N = 189). We defined the fall risk index 5 items version (FRI-5) ≥6 points as the fall risk group. LS was evaluated by stand-up test, two-step test, and 25-Geriatric Locomotive Function Scale (GLFS-25). We divided the subjects into two groups according to the presence or absence of fall risk, and investigated factors associated with fall risk., Results: The fall risk group (30 patients, 15.9%) had higher GLSF-25 (P = 0.001). The results of logistic regression analysis adjusted for age, sex, BMI, and knee osteoarthritis revealed that GLFS-25 (OR: 1.052; 95%CI: 1.009-1.097) was independent factor associated with fall risk. In the ROC analysis, the optimal cut-off value of the GLFS-25 to predict fall risk was 12, which is equivalent to LS stage 1 (AUC 0.688; 95% CI: 0.588-0.787; sensitivity: 0.467, specificity: 0.836)., Conclusions: GLFS-25 was associated with fall risk among community-dwelling elderly individuals aged 65 and over., Competing Interests: Conflict of interest statement Hiroki Iida, Taisuke Seki, Yasuhiko Takegami, Yusuke Osawa, Kato Daisaku, Genta Takemoto, Kei Ando, Shinya Ishizuka, Yukiharu Hasegawa, and Shiro Imagama declare that they have no conflict of interest., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Rapid qualitative antigen testing is essential in the clinical management of COVID-19. However, most evaluations of antigen tests have been performed before the emergence of the Omicron variant., Methods: This prospective observational study evaluated QuickNavi-COVID19 Ag, a rapid antigen detection test between December 2021 and February 2022 in Japan, using real-time reverse transcription (RT)-PCR as a reference. Two nasopharyngeal samples were simultaneously collected for antigen testing and for RT-PCR. Variant analysis of the SARS-CoV-2 genomic sequencing was also performed., Results: In total, nasopharyngeal samples were collected from 1073 participants (417 positive; 919 symptomatic; 154 asymptomatic) for analysis. Compared with those of RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 94.2% (95% CI: 91.6%-96.3%), 99.5% (95% CI: 98.7%-99.9%), 99.2% (95% CI: 97.8%-99.8%), and 96.5% (95% CI: 94.8%-97.7%), respectively. The sensitivity among symptomatic individuals was 94.3% (95% CI: 91.5%-96.4%). Overall, 85.9% of sequences were classified as Omicron sublineage BA.1, 12.4% were Omicron sublineage BA.2, and 1.6% were Delta B.1.617.2. (Delta variant). Most of the samples (87.1%) had Ct values of <25, and the sensitivity was 47.4% for low viral load samples (Ct ≥ 30); a similar trend has been observed in both symptomatic and asymptomatic groups., Conclusions: The QuickNavi-COVID19 Ag test showed sufficient diagnostic performance for the detection of the SARS-CoV-2 Omicron sublineages BA.1 and BA.2 from nasopharyngeal samples. However, the current study was mainly performed in symptomatic patients and the results are not sufficiently applicable for asymptomatic patients., Competing Interests: Declaration of competing interest Denka Co., Ltd. provided funds for research expenses the QuickNavi-COVID19 Ag tests without charge. Hiromichi Suzuki received a lecture fee from Otsuka Pharmaceutical Co., Ltd. Daisuke Kato, Miwa Kuwahara and Shino Muramatsu work for Denka Co., Ltd., the developer of the QuickNavi-COVID19 Ag tests. The Ct values for RT-PCR were determined using the NIID (N2 gene), Japan method [22], 6 positive samples were excluded because the samples were found to be negative by the NIID method, and positive results were determined by Xpert Xpress SARS-CoV-2 and the GeneXpert System. The Ct values for RT-PCR were determined using the NIID (N2 gene), Japan method [22], 5 positive samples were excluded because the samples were found to be negative by the NIID method, and positive results were determined by Xpert Xpress SARS-CoV-2 and the GeneXpert System. The Ct values for RT-PCR were determined using the NIID (N2 gene), Japan method [22], 1 positive sample was excluded because the samples were found to be negative by the NIID method, and positive results were determined by Xpert Xpress SARS-CoV-2 and the GeneXpert System., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Each oligodendrocyte (OC) forms myelin approximately in around 10 different axons to coordinate information transfer by regulating conduction velocity in the central nervous system (CNS). In the classical view, myelin has been considered a static structure that rarely turns over under healthy conditions because myelin tightly holds axons by their laminar complex structure. However, in recent decades, the classical views of static myelin have been renewed with pioneering studies that showed plastic changes in myelin throughout life with new experiences, such as the acquisition of new motor skills and the formation of memory. These changes in myelin regulate conduction velocity to optimize the temporal pattern of neuronal circuit activity among distinct brain regions associated with skill learning and memory. Here, we introduce pioneering studies and discuss the implications of plastic myelin on neural circuits and brain function., (Copyright © 2022 Japan Neuroscience Society and Elsevier Ltd. All rights reserved.)

Holographic structured illumination combined with optogenetics enables patterned stimulation of neurons and glial cells in an intact living brain. Moreover, in vivo functional imaging of cellular activity with recent advanced microscope technologies allows for visualization of the cellular responses during learning, emotion and cognition. Integrating these techniques can be used to verify the link between cell function and behavior output. However, there are technical limitations to stimulate multiple cells with high spatial and temporal resolution with available techniques of optogenetic stimulation. Here, we summarized a two-photon microscope combined with holographic system to stimulate multiple cells with high spatial and temporal resolution for living mice and their biological application., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Since respiratory sample collection is an uncomfortable experience, simultaneous detection of pathogens with a single swab is preferable. We prospectively evaluated the clinical performance of a newly developed antigen test QuickNavi-Flu+COVID19 Ag (Denka Co., Ltd., Tokyo, Japan) which can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses at the same time with a single testing device., Methods: We included those who were suspected of contracting coronavirus disease 2019 (COVID-19) and were referred to a PCR center at Ibaraki prefecture in Japan, between August 2, 2021 to September 13, 2021, when the variant carrying L452R spike mutation of SARS-CoV-2 were prevalent. Additional nasopharyngeal samples and anterior nasal samples were obtained for the antigen test and were compared with a reference real-time reverse transcription PCR (RT-PCR) using nasopharyngeal samples., Results: In total, 1510 nasopharyngeal samples and 862 anterior nasal samples were evaluated. During the study period, influenza viruses were not detected by QuickNavi-Flu+COVID19 Ag and reference real-time RT-PCR. For SARS-CoV-2 detection in nasopharyngeal samples, the sensitivity and specificity of the antigen test were 80.9% and 99.8%, respectively. The sensitivity and specificity using anterior nasal samples were 67.8% and 100%, respectively. In symptomatic cases, the sensitivities increased to 88.3% with nasopharyngeal samples and 73.7% with anterior nasal samples. There were three cases of discrepant results between the antigen test and the real-time RT-PCR. All of them were positive with the antigen test but negative with the real-time RT-PCR in SARS-CoV-2 detection., Conclusion: A combo kit, QuickNavi-Flu+COVID19 Ag, showed an acceptable sensitivity and sufficient specificity for SARS-CoV-2 detection, especially using nasopharyngeal sample collected from symptomatic patients., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Antigen tests for severe acute respiratory coronavirus 2 sometimes show positive lines earlier than their specified read time, although the implication of getting the results at earlier time is not well understood., Methods: We prospectively collected additional nasopharyngeal samples from patients who had already tested positive for SARS-CoV-2 by reverse transcription PCR. The swab was used for an antigen test, QuickNavi™-COVID19 Ag, and the time periods to get positive results were measured., Results: In 84 of 96 (87.5%) analyzed cases, the results of QuickNavi™-COVID19 Ag were positive. The time to obtain positive results was 15.0 seconds in median (inter quartile range: 12.0-33.3, range 11-736) and was extended in samples with higher cycle thresholds (p < 0.001). Positive lines appeared within a minute in 85.7% of cases and within 5 min in 96.4%., Conclusion: QuickNavi™-COVID19 Ag immediately showed positive results in most cases, and the time to a positive reaction may have indicated the viral load., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Antigen testing may help screen for and detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in asymptomatic individuals. However, limited data regarding the diagnostic performance of antigen tests for this group are available., Methods: We used clinical samples to prospectively evaluate the analytical and clinical performance of the antigen test QuickNavi™-COVID19 Ag. This study was conducted at a PCR center between October 7, 2020 and January 9, 2021. Two nasopharyngeal samples per patient were obtained with flocked swabs; one was used for the antigen test, and the other for real-time reverse transcription PCR (RT-PCR). The diagnostic performance of the antigen test was compared between asymptomatic and symptomatic patients, and the RT-PCR results were used as a reference., Results: Among the 1934 collected samples, 188 (9.7%) demonstrated detection of SARS-CoV-2 by real-time RT-PCR; 76 (40.4%) of these 188 samples were from asymptomatic individuals, and over half of the total samples were asymptomatic (1073; 55.5%). The sensitivity of the antigen test was significantly lower for the asymptomatic group than for symptomatic patients (67.1% vs. 89.3%, respectively, p < 0.001). The specificity was 100% for both groups, and no false positives were observed among all 1934 samples. The median cycle threshold value for the asymptomatic group was significantly higher than that of the symptomatic group (24 vs. 20, p < 0.001)., Conclusions: The QuickNavi™-COVID19 Ag showed lower sensitivity for the asymptomatic group than for symptomatic patients. However, its specificity was consistently high, and no false positives were found in this study., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: The rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required to prevent the spread of COVID-19. This study evaluated the utility of two SARS-CoV-2 antigen detection methods., Methods: We evaluated two types of antigen detection methods using immunochromatography (Espline) and quantitative chemiluminescent enzyme immunoassay (Lumipulse). RT-PCR was performed as a standard procedure for COVID-19 diagnosis. Lumipulse and RT-PCR were performed for all 486 nasopharyngeal swabs and 136 saliva samples, and the Espline test was performed for 271 nasopharyngeal swabs and 93 saliva samples., Results: The sensitivity and specificity of the Espline test were 10/11 and 260/260 (100%), respectively for the nasopharyngeal swabs and 3/9 and 84/84 (100%), respectively for the saliva samples. High sensitivities for both saliva (8/9) and nasopharyngeal swabs (22/24) were observed in the Lumipulse test. The specificities of the Lumipulse test for nasopharyngeal swabs and saliva samples were 460/462 (99.6%) and 123/127 (96.9%), respectively., Conclusion: The Espline test is not effective for saliva samples but is useful for simple and rapid COVID-19 tests using nasopharyngeal swabs because it does not require special devices. The Lumipulse test is a powerful high-throughput tool for COVID-19 diagnosis because it has high detection performance for nasopharyngeal swabs and saliva samples., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Postoperative aneurysmal formation of the anomalous artery stump has been reported in the systemic arterial supply to the basal segment of the left lung, whereas the effective preventive strategy remains unclear. Herein we report a case successfully treated with a new external corset technique of an anomalous artery stump. A 54-year-old man with a history of repeated hemoptysis underwent a left lower lobectomy. The anomalous artery stump with a 1.1 cm diameter was wrapped using woven Dacron vascular graft. No aneurysmal change has been observed in the computed tomography obtained after 3 years of follow-up., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Oligodendrocytes, which form the myelin sheaths that insulate axons, regulate conduction velocity. Myelinated axons make up the brain's white matter and contribute to the efficiency of information processing by regulating the timing of neural activity. Traditionally, it has been thought that myelin is a static, inactive insulator around the axon. However, recent studies in humans using magnetic resonance imaging have shown that structural changes in the white matter occur during learning and training, suggesting that 1) white matter change depends on neural activity and 2) activity-dependent changes in white matter are essential for learning and behavior. Furthermore, suppression of oligodendrocytes and their progenitor cells leads to deficits in motor learning and remote fear memory consolidation, suggesting a causal relationship between glial function and the learning process. However, for technical reasons, it remains unclear how myelin-generating glia modulate neural circuitry and what underlying mechanisms they employ to affect learning and behavior. Recent advances in optical and genetic techniques have helped elucidate this mechanism. In this review, we highlight evidence that neural activities regulated by myelin plasticity play a pivotal role in learning and behavior and provide further insight into possible therapeutic targets for treating diseases accompanied by myelin impairment., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Several antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide, but their clinical utility has not been well established. In this study, we evaluated the analytical and clinical performance of QuickNavi™-COVID19 Ag, a newly developed antigen test in Japan., Methods: This prospective observational study was conducted at a PCR center between October 7 and December 5, 2020. The included patients were referred from a local public health center and 89 primary care facilities. We simultaneously obtained two nasopharyngeal samples with flocked swabs; one was used for the antigen test and the other for real-time reverse transcription PCR (RT-PCR). Using the results of real-time RT-PCR as a reference, the performance of the antigen test was evaluated., Results: A total of 1186 patients were included in this study, and the real-time RT-PCR detected SARS-CoV-2 in 105 (8.9%). Of these 105 patients, 33 (31.4%) were asymptomatic. The antigen test provided a 98.8% (95% confidence interval [CI]: 98.0%-99.4%) concordance rate with real-time RT-PCR, along with a sensitivity of 86.7% (95% CI: 78.6%-92.5%) and a specificity of 100% (95% CI: 99.7%-100%). False-negatives were observed in 14 patients, 8 of whom were asymptomatic and had a low viral load (cycle threshold (Ct) > 30). In symptomatic patients, the sensitivity was 91.7% (95% CI: 82.7%-96.9%)., Conclusion: QuickNavi™-COVID19 Ag showed high specificity and sufficient sensitivity for the detection of SARS-CoV-2. This test is a promising potential diagnostic modality especially in symptomatic patients., Competing Interests: Declaration of competing interest Denka Co., Ltd., provided fees for research expenses and the QuickNavi™-COVID19 Ag kits without charge. Hiromichi Suzuki received a lecture fee from Otsuka Pharmaceutical Co., Ltd., regarding this study. Daisuke Kato, Miwa Kuwahara and Shino Muramatsu belong to Denka Co., Ltd., the developer of the QuickNavi™-COVID19 Ag., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Antidepressants are among the most commonly detected pharmaceuticals in the aquatic environment. As they modulate neurotransmission in nervous systems, behavioural abnormalities among aquatic species are of concern. It is possible to measure the concentrations of selected antidepressants by chemical analysis, but other non-target antidepressants and active metabolites might also be present. Here, we propose an "in vitro monoamine transporter inhibition assay" to measure the biological activity of antidepressants, particularly monoamine transporter inhibitors, in wastewater. We used APP, a fluorescent substrate for monoamine transporters, to measure the activity of wastewater extracts at inhibiting APP uptake through the human serotonin transporter (hSERT), norepinephrine transporter (hNET), and dopamine transporter, and the zebrafish SERT (zSERT). We confirmed that the assay could measure the biological activity of test antidepressants. Interestingly, the IC 50 values of antidepressants (the concentration that gave a 50% reduction of APP uptake) for the zSERT were smaller than those for the hSERT. For example, IC 50 value of desipramine for the zSERT was 1/200 of that for the hSERT. These results indicate that antidepressants inhibited zSERT more strongly than hSERT. Then we applied the assay to extracts of effluent from municipal wastewater treatment plants and detected biological activity of antidepressants specifically against the hSERT, hNET, and zSERT for the first time. For the hSERT, antidepressant-equivalent quantities (EQs) ranged from 2.2 × 10 1 to 2.5 × 10 2  ng-clomipramine-EQ/L. For the hNET, EQs ranged from below limit of detection to 8.2 × 10 1  ng-desipramine-EQ/L. For the zSERT, EQs ranged from 2.8 × 10 2 to 3.3 × 10 2  ng-duloxetine-EQ/L. The in vitro monoamine transporter inhibition assay is thus useful for measuring the biological activity of antidepressants in the aquatic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cholinergic neural activation from the medial septal nucleus to hippocampus plays a crucial role in episodic memory as a regulating system for glutamatergic neural activation in the hippocampus. As a candidate regulating factor for acetylcholine synthesis in the medial septal nucleus, hippocampal cholinergic neurostimulating peptide (HCNP) was purified from the soluble fraction of young adult rat hippocampus. HCNP is released from its precursor protein (HCNP-pp), also referred to as phosphatidylethanolamine-binding protein 1. We recently reported that HCNP-pp conditional knockout (KO) mice, in which the HCNP-pp gene was knocked out at 3 months of age by tamoxifen injection, display no significant behavioral abnormalities, whereas HCNP-pp KO mice have a diminished cholinergic projection to CA1 and a decreased of theta activity in CA1. In this study, to address whether HCNP-pp reduction in early life is associated with behavioral changes, we evaluated the behavior of HCNP-pp KO mice in which HCNP-pp was downregulated from an early phase (postnatal days 14-28). As unexpected, HCNP-pp KO mice had no behavioral deficits. However, a significant positive correlation between HCNP-pp and gamma-aminobutyric acid A (GABA A ) receptor α3 subunit mRNA expression was found in individuals. This finding suggests involvement of HCNP-pp in regulating GABA A receptor α3 gene expression., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Thoracoscopic sleeve lobectomy is challenging, considering the technical difficulty in controlling the needle angle and thread through the port. However, effective simulation of the procedure remains to be established. Here, we describe our first experience with thoracoscopic sleeve lobectomy simulation using a three-dimensional printed thoracic model and a handmade rolled sponge. Owing to the transparent structure, we could simultaneously confirm the suturing technique through the monitor (two-dimensional) and direct vision (three-dimensional). We are certain that our realistic and easily repeatable simulation will assist in developing better technique and conduct feasible thoracoscopic sleeve lobectomy., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Bronchopleural fistula (BPF) is a fatal complication after lung cancer surgery. We report the case of a 56-year-old man treated with omental flap for BPF after pneumonectomy along with descending aorta replacement. He underwent left pneumonectomy with combined resection of the descending aorta, followed by replacement with prosthetic graft after the diagnosis of lung cancer, cT4 N1 M0 stage IIIA. He had BPF postoperatively and underwent an omental flap plombage after unsuccessful repair using the latissimus dorsi muscle. He did not have BPF recurrence or aortic graft infection. An omental flap is a useful option for treating BPF with an intrathoracic prosthetic graft., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This report described the experience of active surveillance culture implemented in response to the identification of a single carbapenemase-producing Escherichia coli in a Japanese university hospital. It revealed a horizontal transmission event and an additional asymptomatic carrier of carbapenemase-producing Escherichia coli with unique drug susceptibility and resistance gene profiles. Early implementation of active surveillance culture as a part of multifaceted infection control measures appeared to be useful to control further transmission of carbapenemase-producing Escherichia coli even in the low endemic facility. Further investigations on the timing and usefulness of active surveillance culture in the control of carbapenemase-producing Enterobacteriaceae would be warranted., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The prognostic nutritional index (PNI), calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (cells/mm 3 ), can reportedly predict postoperative complications and prognosis for various types of malignancy. However, the clinical significance and prognostic value of the PNI for both short- and long-term outcomes remains uncertain in patients with lung cancer., Methods: We retrospectively reviewed 248 patients with completely resected non-small cell lung cancer (NSCLC). Clinicopathologic characteristics were evaluated according to the PNI, and the prognostic significance for postoperative outcomes was assessed using Cox proportional regression analysis. The survival rate was calculated using the Kaplan-Meier method., Results: An optimal cutoff of 48 for recurrence-free survival (RFS) was determined using the minimum p value approach. Old age, low body mass index, large tumor size, and elevated C-reactive protein levels correlated significantly with low PNI. Logistic regression analysis demonstrated that low PNI status was statistically related to postoperative complications (Clavien-Dindo grade ≥II) and pulmonary air leakage. Five-year overall survival (OR) rates in the high- and low-PNI groups were 80.6% and 58.5%, respectively (p = 0.002). Five-year RFS rates were 73.6% and 48.6%, respectively (p < 0.001). Furthermore, PNI was identified as an independent prognostic factor for OS (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.08-4.21) and RFS (HR, 2.57; 95% CI, 1.46-4.38) by multivariate analysis., Conclusions: The PNI could represent a useful biomarker to predict postoperative complications and survival in patients with completely resected NSCLC., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Pneumococcal biliary tract infections (PBTIs) were reported as rare due to the bacterium's bile solubility. The purpose of this study was to determine the occurrence and clinical characteristics of PBTIs. A retrospective case series review was conducted from January 2006 to August 2014 at a tertiary referral university hospital in Japan. Patients with a blood or bile culture positive for Streptococcus pneumoniae diagnosed with definite cholangitis or cholecystitis according to Tokyo Guideline 2013 were enrolled in this study. Data on clinical information, treatments, and outcomes were collected. During 104 months, 48 cases of positive blood cultures and 13 cases of positive bile cultures were recorded, and after excluding 43 and 5 of these, respectively, a total of 10 patients were diagnosed with PBTI. Most patients (9/10) had biliary tract problems and biliary devices in place. PBTIs were not rare; conversely, they were a relatively common cause of pneumococcal bacteremia in this center treating a high volume of biliary tract illnesses., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The crotonylation of histones is an important post-translational modification, and epigenetically functions in the regulation of genomic DNA activity. The histone modifications in the structured "histone-fold" domains are considered to have an especially important impact on the nucleosome structure and dynamics. In the present study, we reconstituted the human nucleosome containing histone H3.2 crotonylated at the Lys122 residue, and determined its crystal structure at 2.56 Å resolution. We found that the crotonylation of the H3 Lys122 residue does not affect the overall nucleosome structure, but locally impedes the formation of the water-mediated hydrogen bond with the DNA backbone. Consistently, thermal stability assays revealed that the H3 Lys122 crotonylation, as well as the H3 Lys122 acetylation, clearly reduced the histone-DNA association., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Iron is an essential metal in the body, but its excessive accumulation causes damage in various organs through free radical production. Iron homeostasis is therefore tightly regulated. However, when iron balance collapses, such as in prolonged transfusion, transferrin (Tf) is fully saturated and non-Tf-bound iron (NTBI) appears in the serum. Monitoring serum NTBI levels is therefore crucial in the assessment of the clinical status of patients with iron overload, since NTBI is associated with cellular and organ damage. Several methods for NTBI determination have been reported, but these are extremely complicated and very few laboratories can quantify NTBI at present., Methods: We established a novel assay system utilizing automated analyzers that are widely used in clinical laboratories for diagnostic testing. In this assay, NTBI is chelated by nitrilotriacetic acid (NTA), after which the iron is reduced and transferred to nitroso-PSAP, a chromogen., Results: The assay shows excellent linearity, reproducibility, and compatibility with HPLC, one of the most reliable conventional methods for NTBI quantification., Conclusions: Our novel method for NTBI measurement is high-throughput and may be a useful and powerful tool in the study of the physiological and clinical importance of NTBI., (Copyright © 2014 Elsevier B.V. All rights reserved.)

During mammalian mitosis, transcription is silenced due to dissociation of transcription factors from DNA and chromosome condensation. At the end of mitosis, transcription is reactivated through chromosome relaxation and reloading of these factors to the DNA. Early G1 genes, which are preferentially reactivated during M/G1 transition, are important for maintenance of cellular function and are known to be strictly regulated. As only few early G1 genes have been identified to date, screening for early G1 genes by genome-wide analysis using nascent mRNA could contribute to the elucidation of the regulatory mechanisms during early G1. Here, we performed a detailed expression analysis for the M/G1 transition of mammalian cells by microarray analysis of nascent mRNA, and identified 298 early G1 genes. Analysis of these genes provides two important insights. Firstly, certain motifs are enriched in the upstream sequences of early G1 genes; from this we could predict candidate cognate transcription factors, including Sp1, which is recruited to the DNA in the early G1 phase. Secondly, we discovered that neighboring genes of early G1 genes were also frequently up-regulated in the G1 phase. Information about these numerous newly identified early G1 genes will likely contribute to an understanding of the regulatory mechanisms of the early G1 genes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Tumor necrosis factor α (TNF-α) is a pleiotropic cytokine mediating inflammatory as well as cell death activities, and is thought to induce chondrocytic chondrolysis in inflammatory and degenerative joint diseases. Selective estrogen receptor modulators (SERMs), such as raloxifene, which are commonly used in clinical settings act as estrogen agonists or antagonists. It is assumed that estrogens have a potential role in cartilage protection; however, the precise molecular mechanism for the protective effects of estrogens is unclear. This study was designed to examine whether raloxifene inhibits TNF-α-induced apoptosis in human chondrocytes and to clarify the mechanisms involved. We also investigated the signaling pathways responsible for the anti-apoptotic effect of raloxifene. Apoptosis in chondrocytes was determined by DNA fragmentation assay and caspase-3 activation. Raloxifene significantly inhibited TNF-α-induced caspase-3 activation and cell DNA fragmentation levels in chondrocytes. The inhibitory effect of raloxifene was abolished by the estrogen receptor antagonist ICI 182,780. Extracellular signal-regulated kinase 1/2 (ERK1/2) regulates apoptosis, acting as an apoptotic or anti-apoptotic signal. TNF-α-induced apoptosis was significantly enhanced by the ERK1/2 pathway inhibitor PD98059. Raloxifene stimulated a further increase in ERK1/2 phosphorylation in TNF-α-treated chondrocytes. Furthermore, the anti-apoptotic effects of raloxifene were inhibited by PD98059. In addition, the anti-apoptotic effects of raloxifene were completely abolished in ERK1/2 siRNA-treated chondrocytes. These results suggest that raloxifene prevents caspase-3-dependent apoptosis induced by TNF-α in human chondrocytes by activating estrogen receptors and the ERK1/2 signaling pathway., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Double strand breaks (DSBs) are the most serious type of DNA damage. DSBs can be generated directly by exposure to ionizing radiation or indirectly by replication fork collapse. The DNA damage tolerance pathway, which is conserved from bacteria to humans, prevents this collapse by overcoming replication blockages. The INO80 chromatin remodeling complex plays an important role in the DNA damage response. The yeast INO80 complex participates in the DNA damage tolerance pathway. The mechanisms regulating yINO80 complex are not fully understood, but yeast INO80 complex are necessary for efficient proliferating cell nuclear antigen (PCNA) ubiquitination and for recruitment of Rad18 to replication forks. In contrast, the function of the mammalian INO80 complex in DNA damage tolerance is less clear. Here, we show that human INO80 was necessary for PCNA ubiquitination and recruitment of Rad18 to DNA damage sites. Moreover, the C-terminal region of human INO80 was phosphorylated, and overexpression of a phosphorylation-deficient mutant of human INO80 resulted in decreased ubiquitination of PCNA during DNA replication. These results suggest that the human INO80 complex, like the yeast complex, was involved in the DNA damage tolerance pathway and that phosphorylation of human INO80 was involved in the DNA damage tolerance pathway. These findings provide new insights into the DNA damage tolerance pathway in mammalian cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We retrospectively analyzed 12 consecutive adult severe aplastic anemia patients who received unrelated umbilical cord blood transplantation after a reduced-intensity conditioning regimen (RI-UCBT). The conditioning regimen consisted of 125 mg/m² fludarabine, 80 mg/m² melphalan, and 4 Gy of total body irradiation. The median infused total nucleated cell number and CD34(+) cell number were 2.50 × 10⁷/kg and 0.76 × 10⁵/kg, respectively. Eleven of the 12 patients achieved primary neutrophil and platelet engraftment. All patients who achieved engraftment had complete hematologic recovery with complete donor chimerism, except for one patient who developed late graft failure 3 years after RI-UCBT. Two of the 12 patients died of idiopathic pneumonia syndrome, and the remaining 10 patients are alive, having survived for a median of 36 months. Our encouraging results indicate that RI-UCBT may become a viable therapeutic option for adult severe aplastic anemia patients who lack suitable human leukocyte antigen-matched donors and fail immunosuppressive therapy.

Sulphated glycosaminoglycans such as heparin inhibit the early step of dengue virus infection through interaction with envelope (E) protein. Here, we found that chondroitin sulphate E (CSE), but not CSD, which contains the same degree of sulphation, inhibited dengue virus (DENV) infection of cells with adsorption. CSE significantly reduced infectivity of all dengue virus serotypes to BHK-21 and Vero cells. DENV preferentially bound to CSE immobilised on plastic plates. Also, virus binding to CSE or heparin was cross-inhibited by soluble CSE or heparin. These findings suggested that common carbohydrate determinants on CSE and heparin could be essential epitopes for interaction of DENV, and may be responsible for inhibition of the early steps of DENV infection. A recombinant E protein directly bound heparin and CSE, but not CSD, meaning that interaction of CSE with E protein contributes to the inhibitory action of this glycosaminoglycan. These observations indicate that a specific carbohydrate structure rather than polysulphation or addition of negative charges of the glycosaminoglycan molecule would be necessary for direct binding to DENV E protein. In conclusion, CSE showed antiviral activity as an entry inhibitor targeting E protein of dengue virus., (Copyright © 2010 Elsevier B.V. All rights reserved.)

We describe the direct electrochemical detection of DNA methylation in relatively long sequences by using a nanocarbon film electrode. The film was formed by employing the electron cyclotron resonance sputtering method and had a nanocrystalline sp(2) and sp(3) mixed bond structure. Our methylation detection technique measures the differences between the oxidation currents of both 5-methylcytosine and cytosine without a bisulfite reaction or labeling. This was possible because this film electrode has a wide potential window while maintaining the high electrode activity needed to quantitatively detect both bases by direct oxidation. By optimizing the electrode surface conditions using electrochemical pretreatment, we used this film to quantitatively detect single cytosine methylation regardless of the methylation position in the sequence including retinoblastoma gene fragments (approximately 24 mers). This was probably due to the high stability of this film electrode, which we achieved by controlling the surface hydrophilicity to suppress the fouling, and by maintaining electrode activity against all the bases. The pH optimization of the oligonucleotide measurements was also useful for distinguishing both bases separately. Under the optimized conditions, this film electrode allowed us to realize the quantitative detection of DNA methylation ratios solely by measuring methylated 5'-cytosine-phosphoguanosine (CpG) repetition oligonucleotides (60 mers) with different methylation ratios., (Copyright 2010 Elsevier Inc. All rights reserved.)

Delayed engraftment or graft failure is one of the major complications after cord blood transplantation (CBT). To investigate factors impacting engraftment, we conducted a retrospective analysis of adult patients who underwent reduced-intensity CBT at our institute, in which preparative regimens mainly consisted of fludarabine, melphalan, and total body irradiation with graft-versus-host (GVH) disease prophylaxis using single calcineurin inhibitors. Among 152 evaluable patients, the cumulative incidence of neutrophil engraftment was 89%. High total nucleated cell and CD34(+) cell dose were associated with the faster speed and higher probability of engraftment. In addition, the degree of human leukocyte antigen (HLA) mismatch in the GVH direction was inversely associated with engraftment kinetics, whereas no statistically significant association was observed with the degree of HLA mismatch in the host-versus-graft direction. Similarly, the number of HLA class I antigens mismatched in the GVH direction, but not in the host-versus-graft direction, showed a negative correlation with engraftment kinetics. HLA disparity did not have significant impact on the development of GVH disease or survival. This result indicates the significant role of HLA disparity in the GVH direction in the successful engraftment, raising the novel mechanism responsible for graft failure in CBT.

We report a case of quadrilateral space syndrome related to thoracic surgery. A 21-year-old man underwent video-assisted thoracic surgery for a left-sided pneumothorax. After the operation, he presented with difficulties in left arm abduction and paresthesia over the lateral aspect of the shoulder and upper arm. Deltoid muscle atrophy and tenderness over the quadrilateral space were also observed. On further examination, he was diagnosed with isolated paralysis of the axillary nerve, the so-called quadrilateral space syndrome. This is a rare complication, but it interferes with the activities of daily living, and thus one should pay attention to this syndrome.

We performed X-ray crystallographic analyses of 6-aminohexanoate-dimer hydrolase (Hyb-24DN), an enzyme responsible for the degradation of nylon-6, an industry by-product, and of a complex between Hyb-24DN-A(112) (S112A-mutant of Hyb-24DN) and 6-aminohexanoate-linear dimer (Ald) at 1.58 A and 1.4 A resolution, respectively. In Hyb-24DN, Asp181-O(delta) forms hydrogen bonds with Tyr170-O(eta), -two of the catalytic and binding amino acids, and a loop between Asn167 and Val177. This state is the so-called open form, allowing its substrate to bind in the space between the loop and catalytic residues. Upon substrate binding (in Hyb-24DN-A(112)/Ald complex), the loop is shifted 4.3 A at Tyr170-C(alpha), and the side-chain of Tyr170 is rotated. By the combined effect, Tyr170-O(eta) moves a total of 10.5 A, resulting in the formation of hydrogen bonds with the nitrogen of amide linkage in Ald (closed form). In addition, electrostatic interaction between Asp181-O(delta) and the amino group in Ald stabilizes the substrate binding. We propose here that the enzyme catalysis proceeds according to the following steps: (i) Ald-induced transition from open to closed form, (ii) nucleophilic attack of Ser112 to Ald and formation of a tetrahedral intermediate, (iii) formation of acyl enzyme and transition to open form, (iv) deacylation. Amino acid substitutions reducing the enzyme/Ald interaction at positions 181 or 170 drastically decreased the Ald-hydrolytic activity, but had very little effect on esterolytic activity, suggesting that esterolytic reaction proceeds regardless of conversion. Present models illustrate why new activity against the nylon oligomer has evolved in an esterase with beta-lactamase folds, while retaining the original esterolytic functions.

Background: At present in Japan, there are neither reports on antibiotic prophylaxis regardless of underlying diseases nor precise guidelines on prophylactic antibiotics in orthopedic surgery. Therefore, the preventive effect of antimicrobial agents on surgical site infection (SSI) after clean orthopedic surgery was studied to control the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in our ward and to reduce SSI caused by MRSA., Methods: Regardless of the type of operation or underlying disease, a regimen of prophylaxis that is of shorter duration than before was conducted in 419 patients admitted to our orthopedic ward (one ward) and who underwent clean orthopedic surgery between 2001 and 2002., Results: The annual usage of beta-lactam antibiotics in the ward decreased by 960.9 g, the isolation rate of MRSA in the ward decreased to 50% (the lowest isolation rate in the past 4 years), and SSIs caused by MRSA were found in 3 of 419 (0.71%) patients in one year compared with 6 of 470 (1.28%) during the previous year. Comparison of two antibiotics revealed that SSI caused by MRSA did not occur in any of the 187 patients receiving sulbactam/ampicillin as prophylaxis but did occur in 1.29% (3/232) patients receiving cefazolin. Concerning all SSIs caused by any organisms, they occurred in 0.53% of patients receiving sulbactam/ampicillin and in 2.16% of patients receiving cefazolin. The difference in the SSI rates between the two groups was not statistically significant., Conclusions: Although there is statistically no significant difference in the incidence of SSI caused by MRSA, we were able to decrease the isolation rates of MRSA and prevent MRSA from spreading owing to the reduced antibiotic usage in this study. Sulbactam/ampicillin can be recommended, as well as cefazolin, for antibiotic prophylaxis in clean orthopedic surgery.

Objectives: The goal of our study was to evaluate the efficacy and safety of a new type of automated cutting needle for tissue-core lung biopsy under real-time CT fluoroscopic guidance., Design: Observational, Materials and Methods: One hundred ten percutaneous needle tissue-core lung biopsies were performed with the Auto Surecut needle (Create Medic; Yokohama, Japan) under CT fluoroscopic guidance, and the specimens obtained underwent histopathologic evaluation. A final diagnosis was confirmed by independent surgical pathology., Results: The rate of success for the diagnosis for specimens that were adequate for histopathologic analysis was 94.5% (104 of 110 specimens). The sensitivity, specificity, and accuracy in diagnosing malignancy were 95.1%, 100%, and 96.2%, respectively. A specific cell type could be characterized in 95.2% of those 104 lesions (99 lesions; malignant, 76 lesions; benign, 23 lesions). The specific cell type was precisely diagnosed, and was confirmed after surgery in 65 malignant lesions and 23 benign lesions. The biopsy-induced complications encountered were pneumothorax in 34.5% (38 of 110 patients) and hemoptysis in 6.4% (7 of 110 patients). No patient had a serious complication., Conclusion: CT fluoroscopy-guided lung biopsy using the Auto Surecut needle provides a high degree of diagnostic accuracy, allows for the specific characterization of lung nodules, and can be performed safely.