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Background: With the standardization of surgical techniques and continuous development of plate fixators, medial open-wedge high tibial osteotomy (OWHTO) has become an option for the treatment of medial knee osteoarthritis. However, it is also associated with several complications. To reduce the risk of these complications, it is essential for surgeons to accurately understand the three-dimensional (3D) anatomical structures, including the surroundings of the surgical field. Gross dissection using a cadaver provides a large surgical field and is the best learning method for studying anatomical structures in three dimensions; however, it is not available at all medical institutions., Methods: One female cadaveric knee, fixed using the Thiel method, was used in this study, and OWHTO was performed. A series of photographs was taken from approximately 60 different angles at each stage of the autopsy for digital photogrammetry to ensure that there was at least a 60% overlap between photographs., Results: Each 3D object was created to be faithful to the original specimen and displayed on an augmented reality headset. It was created to capture the subtle nuances of irregular shapes and structures, highlighting the unique ability of photogrammetry to capture pathology. This method allows surgeons to visualize the location of neurovascular injuries in the intraoperative field of view., Conclusions: Using a technique that applies digital photogrammetry to create 3D objects from handheld photographs, this reports for the first time an educational tool that can reproduce the anatomy related to high tibial osteotomy in three dimensions., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Tibial footprint of anterior cruciate ligament (ACL) is situated close to the anterior lateral meniscal root (ALMR) attachment., Purpose: To investigate the impact of the size and location of the tibial tunnel for ACL reconstruction on the ACL footprint coverage and overlap to the ALMR., Study Design: Controlled laboratory study., Methods: Twenty knee MRI scans from twenty healthy subjects were recruited, and three-dimensional (3D) tibia models were created to show the tibial attachment sites of ACL and ALMR. Surgical simulation of the tibial tunnel drilling was performed on each 3D model, entering the joint at an angle set at 60 degrees from the tibial plateau plane and 55 degrees from the posterior tibial condylar axis, with analysis for six different drill sizes; 7.5, 8, 8.5, 9, 9.5 and 10 mm; and nine locations; the center of the ACL attachment and eight locations 2% of the tibial width apart surrounding it. The width of the tibial plateau, the distance between ACL and ALMR attachment centers, and the size and location of the potential tibial tunnel were evaluated to determine association with the area of the ACL footprint coverage and ALMR overlap using a linear mixed effects model., Results: A large tunnel (p <.001), a central and anterior location (p <.029), and small tibial width (p =.015) were all associated with larger coverage of the ACL footprint. A large tunnel (p <.001), posteriorly and laterally located (p ≤ 0.001), and a small distance between the ACL and ALMR centers (p =.001) were significantly associated with a larger ALMR overlap. The association of the tunnel size to ALMR overlap reduced with a medial tunnel location., Conclusions: The short distance between the centers of the ALMR attachment and native ACL footprint suggests that the ALMR will always be susceptible to overlap when the tibial tunnel is drilled in ACL reconstruction. Small alterations in tunnel location can lead to a statistically significant alteration with the amount of ALMR overlap. To minimize this overlap, whilst maintaining acceptable coverage of the ACL footprint, a tibial tunnel positioned in a medial or anteromedial location from the center of the ACL footprint is recommended., 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 © 2022 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, the neuropathological formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. The best cellular correlates of the early cognitive deficits in AD patients are synapse loss and gliosis. In particular, it is unclear whether the activation of microglia (microgliosis) has a neuroprotective or pathological role early in AD. Here we report that microgliosis is an early mediator of synaptic dysfunction and cognitive impairment in APP/PS1 mice, a mouse model of increased amyloidosis. We found that the appearance of microgliosis, synaptic dysfunction and behavioral impairment coincided with increased soluble Aβ 42 levels, and occurred well before the presence of Aβ plaques. Inhibition of microglial activity by treatment with minocycline (MC) reduced gliosis, synaptic deficits and cognitive impairments at early pathological stages and was most effective when provided preventive, i.e., before the onset of microgliosis. Interestingly, soluble Aβ levels or Aβ plaques deposition were not affected by preventive MC treatment at an early pathological stage (4 months) whereas these were reduced upon treatment at a later stage (6 months). In conclusion, this study demonstrates the importance of early-stage prevention of microgliosis on the development of cognitive impairment in APP/PS1 mice, which might be clinically relevant in preventing memory loss and delaying AD pathogenesis., 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 © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Splenic hilar lymphadenectomy is not recommended for advanced proximal gastric cancer that does not invade the greater curvature according to the results of the previous studies. The efficacy of splenic hilar lymphadenectomy for type II and type III adenocarcinomas of the esophagogastric junction and easy spread to the greater curvature of the stomach remains unclear. This study aimed to investigate the efficacy of splenic hilar lymphadenectomy and identify the risk factors for metastasis to splenic hilar nodes., Methods: We examined patients who underwent R0/1 gastrectomy for Siewert types II and III at a single high-volume center in Japan. We analyzed the metastatic incidence, therapeutic value index, and risk factors for splenic hilar lymph node metastasis., Results: We examined 126 patients (74, type II; 52, type III). Splenectomy was performed in 76 patients. Metastatic incidence and the therapeutic value index of splenic hilar lymph nodes in patients with type II and type III tumors were 4.5% and 0, and 21.9% and 9.4, respectively. In the patients who underwent splenectomy, we identified Siewert type III tumors (odds ratio: 6.93, 95% confidence interval: 1.24-38.8, p = 0.027) and tumor location other than the lesser curvature (odds ratio: 7.36, 95% confidence interval: 1.32-41.1, p = 0.023) to be independent risk factors. The metastatic incidence (46.2%) and therapeutic value index (15.4) were high in patients with both risk factors., Conclusions: Splenic hilar lymphadenectomy may contribute to the survival of patients with Siewert type III tumors, especially when the predominant location is not the lesser curvature., Competing Interests: Declaration of competing interest Yasushi Rino has received speaker honorariums and research grants from Daiichi Sankyo, Johnson & Johnson, Otsuka, Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Abbott Nutrition, Asahi Kasei, Tsumura & Co., Covidien, Zeria Pharmaceutical and EA Pharma. The other authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Cancer cells rely on glycolysis to generate ATP for survival. However, inhibiting glycolysis is insufficient for the eradication of cancer cells because glycolysis-suppressed cells undergo metabolic reprogramming toward mitochondrial oxidative phosphorylation. We previously described that upon glycolytic suppression in pancreatic cancer cells, intracellular glycometabolism is shifted toward mitochondrial oxidative phosphorylation in an autophagy-dependent manner for cellular survival. Here, we hypothesized that mitophagy, which selectively degrades mitochondria via autophagy, is involved in mitochondrial activation under metabolic reprogramming. We revealed that glycolytic suppression notably increased mitochondrial membrane potential and mitophagy in a pancreatic cancer cell model (PANC-1). PTEN-induced kinase 1 (PINK1), a ubiquitin kinase that regulates mitophagy in healthy cells, regulated mitochondrial activation through mitophagy by glycolytic suppression. However, Parkin, a ubiquitin ligase regulated by PINK1 in healthy cells to induce mitophagy, was not involved in the PINK1-dependent mitophagy of the cancer glycometabolism. These results imply that cancer cells and healthy cells have different regulatory pieces of machinery for mitophagy, and inhibition of cancer-specific mechanisms may be a potential strategy for cancer therapy targeting metabolic reprogramming., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection., Objectives: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS)., Methods: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness., Results: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7., Conclusions: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Antibiotic-loaded acrylic cement beads have a large surface area and excellent sustained-release properties. However, there are some difficulty manufacturing reasonably sized beads and their careful handling. We developed a self-made cement bead maker using a mold of a sphere with a diameter of 8 and 10 mm with a 2-mm-diameter connecting hole. With this instrument, approximately 32 beads can be made from 40 g of bone cement. We clinically applied this technique to 11 cases of periprosthetic joint infection. There was no recurrence of infection noted. The advantages of this device were that it was possible to adjust the combination of antimicrobial agents and that the shape was uniform and easy to handle during surgery., (© 2021 The Authors.)

Casein hydrolysate (Pep) is a dispersant for poorly water-soluble drugs and nutraceutical ingredients. However, two types of complexes may be between Pep and poorly water-soluble molecules: those that are (1) dispersed as hydrocolloids in aqueous media with a particle size of 100-500 nm; and (2) not hydrocolloids, as indicated by permeability of the complex through an ultrafiltration (UF) membrane and the fact that the particle size is ambiguous by dynamic light scattering. This study was conducted to clarify the factors that determine the dissolution state of the complexes between poorly water-soluble ingredients and casein hydrolysate. We classified the dissolution state of the complexes between poorly water-soluble ingredients and Pep by the permeability using a UF membrane. Complexes containing larger and more-hydrophobic molecules are hydrocolloids and do not permeate the UF membrane, whereas complexes containing comparatively smaller and less-hydrophobic molecules do permeate the UF membrane. A complex containing indomethacin, which has borderline solubility properties, does not permeate the UF membrane at pH values in which the indomethacin carboxylic acid group is protonated, but it is permeable at pH values in which its carboxylic acid group is deprotonated. Furthermore, we determined the stoichiometry and association constant for the complex between a major peptide in Pep and poorly water-soluble resveratrol (Res) based on fluorescence quenching. We calculated the stoichiometry of Res and PepY to be 2:3 and the association constant to be 2.4 × 10 7 M -1 ., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Neonatal hypoxic-ischemic encephalopathy (nHIE) is a major neonatal brain injury. Despite therapeutic hypothermia, mortality and sequelae remain severe. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with the pathophysiology of nHIE. In this study, morphologic change and microglial activation under the nHIE condition and LOX-1 treatment were investigated. The microglial activity and proliferation were assessed with a novel morphologic method, immunostaining, and quantitative PCR in the rat brains of both nHIE model and anti-LOX-1 treatment. Circumference ratio, the long diameter ratio, the cell area ratio, and the roundness of microglia were calculated. The correlation of the morphologic metrics and microglial activation in nHIE model and anti-LOX-1 treated brains was evaluated. LOX-1 was expressed in activated ameboid and round microglia in the nHIE model rat brain. In the evaluation of microglial activation, the novel morphologic metrics correlated with all scales of the nHIE-damaged and treated brains. While the circumference and long diameter ratios had a positive correlation, the cell area ratio and roundness had a negative correlation. Anti-LOX-1 treatment attenuated morphologic microglial activation and proliferation, and suppressed the subsequent production of inflammatory mediators by microglia. In human nHIE, round microglia and endothelial cells expressed LOX-1. The results indicate that LOX-1 regulates microglial activation in nHIE and anti-LOX-1 treatment attenuates brain injury by suppressing microglial activation., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: The optimal anterolateral procedure to control anterolateral rotational laxity of the knee is still unknown. The objective was to compare the ability of five anterolateral procedures performed in combination with anterior cruciate ligament reconstruction (ACLR) to restore native knee kinematics in the setting of a deficient anterior cruciate ligament (ACL) and anterolateral structures., Methods: A controlled laboratory study was performed using 10 fresh-frozen cadaveric whole lower limbs with intact iliotibial band. Kinematics from 0° to 90° of flexion were recorded using a motion analysis three-dimensional (3D) optoelectronic system, allowing assessment of internal rotation (IR) and anteroposterior (AP) tibial translation at 30° and 90° of flexion. Joint centres and bony landmarks were calculated from 3D bone models obtained from CT scans. Intact knee kinematics were assessed initially, followed by sequential section of the ACL and anterolateral structures (anterolateral ligament, anterolateral capsule and Kaplan fibres). After ACLR, five anterolateral procedures were performed consecutively on the same knee: ALLR, modified Ellison, deep Lemaire, superficial Lemaire and modified MacIntosh. The last three procedures were randomised. For each procedure, the graft was fixed in neutral rotation at 30° of flexion and with a tension of 20 N., Results: Isolated ACLR did not restore normal overall knee kinematics in a combined ACL plus anterolateral-deficient knee, leaving a residual tibial rotational laxity (p=0.034). Only the ALLR (p=0.661) and modified Ellison procedure (p=0.641) restored overall IR kinematics to the normal intact state. Superficial and deep Lemaire and modified MacIntosh tenodeses overconstrained IR, leading to shifted and different kinematics compared with the intact condition (p=0.004, p=0.001 and p=0.045, respectively). Compared with ACLR state, addition of an anterolateral procedure did not induce any additional control on AP translation at 30° and 90° of flexion (all p>0.05), except for the superficial Lemaire procedure at 90° (p=0.032)., Conclusion: In biomechanical in vitro setting, a comparison of five anterolateral procedures revealed that addition of either ALLR or modified Ellison procedure restored overall native knee kinematics in a combined ACL plus anterolateral-deficient knee. Superficial and deep Lemaire and modified MacIntosh tenodeses achieved excellent rotational control but overconstrained IR, leading to a change from intact knee kinematics., Level of Evidence: The level-of-evidence statement does not apply for this laboratory experiments study., Competing Interests: Competing interests: None declared., (© International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Given the common occurrence of residual laxity and re-injury post anterior cruciate ligament reconstruction (ACLR), additional anterolateral procedures are increasingly used in combination with an ACLR. Despite the perception that there is a risk of over-constraining the lateral tibiofemoral (LTF) compartment, potentially leading to osteoarthritis, assessment on their effect on intra-articular compartment pressures is still lacking. Our objective was therefore, through a pilot biomechanical study, to compare LTF contact pressures after the most commonly used anterolateral procedures., Methods: A controlled laboratory pilot study was performed using 4 fresh-frozen cadaveric whole lower limbs. Through 0° to 90° of flexion, LTF contact pressures were measured with a Tekscan sensor, located under the lateral meniscus. Knee kinematics were obtained in 3 conditions of rotation (NR: neutral, ER: external and IR: internal rotation) to record the position of the knees for each loading condition. A Motion Analysis system with a coordinate system based on CT scans 3D bone modelling was used. After an ACLR, defined as the reference baseline, 5 anterolateral procedures were compared: anterolateral ligament reconstruction (ALLR), modified Ellison, deep Lemaire, superficial Lemaire and modified MacIntosh procedures. The last 3 procedures were randomised. For each procedure, the graft was fixed in NR at 30° of flexion and with a tension of 20 N., Results: Compared with isolated ACLR, addition of either ALLR or modified Ellison procedure did not increased the overall LTF contact pressure (all p>0.05) through the full range of flexion for the IR condition. Conversely, deep Lemaire, superficial Lemaire and modified MacIntosh procedure (all p<0.05) did increase the overall LTF contact pressure compared with ACLR in IR. No significant difference was observed in ER and NR conditions., Conclusion: This pilot study, comparing the main anterolateral procedures, revealed that addition of either ALLR or modified Ellison procedure did not change the overall contact pressure in the LTF compartment through 0° to 90° of knee flexion. In contrast, the deep and superficial Lemaire, and modified MacIntosh procedures significantly increased overall LTF contact pressures when the knee was internally rotated., Competing Interests: Competing interests: None declared., (© International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There has been increased use of adjustable suspensory fixation (ASF) for anterior cruciate ligament reconstruction (ACLR). Potential benefits are the ability to use a shorter graft and to prevent graft displacement and damage. The purpose of this study was to establish the efficacy of this fixation method and assess whether it leads to less tunnel widening, and avoids known complications of screw fixation., Methods: Thirty-eight patients who underwent ACLR with ASF on both the femoral and tibial sides met the inclusion criteria and were propensity matched demographically with 38 patients who underwent hybrid fixation with femoral suspensory and tibial screw and sheath. At one-year, KT-1000 knee laxity measurements were recorded and detailed MRI analysis looking at tunnel aperture widening, tunnel appearance, graft integration within the tunnels, and graft healing., Results: MRI comparison between ASF and hybrid cohorts revealed no significant differences in graft signal or integration, and clinically there were no differences in knee laxity between cohorts (mean 1.5 mm ± 2.0 and 1.5 mm ± 2.3 (n.s.) in the ASF and hybrid fixation respectively). Significantly less aperture tibial tunnel widening (2.2 mm versus 4.4 mm, p < 0.0001) and tibial cysts (2 versus 9, p = 0.047) were observed in the ASF cohort, whilst mean femoral tunnel widening was comparable between both cohorts (ASF 2.8 mm, hybrid 3.2 mm; n.s.)., Conclusions: Hamstring autografts for ACLR fixed using either ASF or a hybrid fixation technique provided comparable knee stability and MRI graft signal intensity. Tibial ASF demonstrated significantly less tibial aperture widening and tunnel cyst formation when compared to screw and sheath fixation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU)., Methods: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD., Results: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR® :  -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165)., Conclusion: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use., Competing Interests: Conflict of interest T Oshima received research grant from the public Foundation Nutrition 2000. M Delsoglio, YM Dupertuis and C Veraar have no conflict of interest. P Singer received nonrestrictive research grants and/or honoraries for lectures from Abbott, Baxter, B Braun, Fresenius-Kabi, Nestle, Nutricia and ART Medical., GE, Cosmed and Mindray. E De Waele received unrestricted research grants from the Belgian Government of Health, Baxter Healthcare, Nutricia, Fresenius Kabi International, B Braun and honoraries for lectures for Baxter, Nutricia, and Fresenius Kabi, none being related to the present study. CP Heidegger received restricted research grants from Fresenius Kabi and Nestlé, none being related to the present study. J Wernerman: received consulting fees and/or honoraries for lectures for Baxter, Fresenius Kabi, GE Health Care, Nestlé, and Nutricia none being related to the present study. P Wischmeyer received grant funding from National Institutes of Health, Canadian Institutes of Health Research, Abbott, Baxter, Fresenius and Takeda, unrestricted gift donations in support of nutrition research from Cosmed and Musclesound, honoraria or travel expenses for CME lectures on improving nutrition care from Abbott, Baxter, and Nutricia. He has served as a consultant to Abbott, Fresenius, Baxter, Cardinal Health, Nutricia and Takeda for ICU nutrition research. MM Berger received unrestricted research grant from Fresenius Kabi International, consulting fees from Fresenius Kabi International, and honoraries for lectures for Fresenius Kabi, Nestlé, and Baxter, none being related to the present study. C Pichard received financial support from research grants and unrestricted academic research grants from the public institutions, as well as no-restrictive research grants and consulting fees from the Foundation Nutrition 2000plus, Abbott, Baxter, B. Braun, Cosmed, Fresenius-Kabi, Nestle Medical Nutrition, Novartis, Nutricia-Numico, Pfizer, Shire and Solvay., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

d-Amino acids are physiologically important components of peptidoglycan in the bacterial cell wall, maintaining cell structure and aiding adaptation to environmental changes through peptidoglycan remodelling. Therefore, the biosynthesis of d-amino acids is essential for bacteria to adapt to different environmental conditions. The peptidoglycan of the extremely thermophilic bacterium Thermus thermophilus contains d-alanine (d-Ala) and d-glutamate (d-Glu), but its d-amino acid metabolism remains poorly understood. Here, we investigated the enzyme activity and function of the product of the TTHA1643 gene, which is annotated to be a Glu racemase in the T. thermophilus HB8 genome. Among 21 amino acids tested, TTHA1643 showed highly specific activity toward Glu as the substrate. The catalytic efficiency (k cat /K m ) of TTHA1643 toward d- and l-Glu was comparable; however, the k cat value was 18-fold higher for l-Glu than for d-Glu. Temperature and pH profiles showed that the racemase activity of TTHA1643 is high under physiological conditions for T. thermophilus growth. To assess physiological relevance, we constructed a TTHA1643-deficient strain (∆TTHA1643) by replacing the TTHA1643 gene with the thermostable hygromycin resistance gene. Growth of the ∆TTHA1643 strain in synthetic medium without d-Glu was clearly diminished relative to wild type, although the TTHA1643 deletion was not lethal, suggesting that alternative d-Glu biosynthetic pathways may exist. The deterioration in growth was restored by adding d-Glu to the culture medium, showing that d-Glu is required for normal growth of T. thermophilus. Collectively, our findings show that TTHA1643 is a Glu racemase and has the physiological function of d-Glu production in T. thermophilus., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest associated with the manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear., Objective: To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease., Methods: We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test., Results: The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593)., Conclusions: These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment., Competing Interests: Declaration of competing interest All authors have no potential conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Meniscal morphology under full weight-loading conditions is currently unknown. This study aimed to evaluate extrusion in the medial meniscus between unloaded and upright-loaded conditions in healthy adults using upright magnetic resonance imaging (MRI) and ultrasonography and to investigate the relationship between MRI and ultrasonography in upright-loaded conditions., Methods: Eighteen healthy adult volunteers (13 men and 5 women) participated in the study. MRI and ultrasonography were performed with patients in the supine, double-leg upright (DLU), and single-leg upright (SLU) positions. Medial, anterior, and posterior extrusions of the medial meniscus against the tibial edge were evaluated and compared across the three positions. Medial extrusion correlations between MRI and ultrasonography were examined. Demographic data and hip-knee-ankle (HKA) angles were measured and correlated with changes in the medial extrusion. The medial meniscal extrusions detected via MRI and ultrasonography were compared across the three positions. Correlations were examined using Pearson's correlation coefficients., Results: Negative correlations were found between the change in medial extrusion of the medial meniscus and HKA angle (MRI: r = -0.52, ultrasonography: r = -0.51). Although no significant differences among the three conditions were observed for the anterior and posterior extrusions of the medial meniscus, the medial extrusion of the medial meniscus was significantly greater in DLU and SLU positions than that in the supine position for MRI and ultrasonography (P < 0.05). Positive correlations for the medial extrusion of the medial meniscus were found between MRI and ultrasonography in all three positions (supine: r = 0.74, DLU; r = 0.71, SLU; r = 0.61)., Conclusions: Although no significant differences in anterior and posterior extrusions of the medial meniscus were seen across the studied positions, the medial meniscus was found to undergo significant medial extrusion during upright weight-loading conditions. The strong correlation between MRI and ultrasonography highlighted the usefulness of ultrasonography., Level of Evidence: Level IV., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Fluoroscopy and navigation systems provide an accurate and reproducible method of guiding anatomical tunnel positioning during anterior cruciate ligament reconstruction (ACLR). The aim was to evaluate the differences in tibial tunnel location assessed by both an intraoperative navigation system and fluoroscopy, validated using a one-week postoperative three-dimensional computed tomography (3DCT)., Methods: The tibial tunnel location in a consecutive series of 35 patients who received a single-bundle ACLR was evaluated by intraoperative navigation system, fluoroscopic image and compared with postoperative 3DCT position. The location to the anterior-posterior (AP) and medial-lateral (ML) direction were compared between all three methods., Results: The tibial tunnel locations were 46.7 ± 4.5%, 44.5 ± 1.9%, and 43.6 ± 2.4% in ML direction, and 42.8 ± 7.6%, 37.9 ± 3.8%, and 37.9 ± 3.7% in AP direction using an intraoperative navigation system, fluoroscopic image and postoperative 3DCT, respectively. Significant differences between the navigation system and fluoroscopic image (ML, P = 0.001; AP, P = 0.006), and the navigation system and 3DCT (ML, P = 0.001; AP, P < 0.001) were seen. However, there was no significant difference between fluoroscopy and 3DCT (ML, P = 0.315; AP, P = 0.999). There was a significant lack of agreement for analyses measured using a navigation system and 3DCT. Fluoroscopy and 3DCT demonstrated an acceptable agreement (ML, r pt  = -0.21, P = 0.232; AP, r pt  = 0.04, P = 0.826)., Conclusions: A tibial tunnel location assessed by intraoperative fluoroscopy shows better agreement and interchangeability with one-week postoperative 3DCT validation during single-bundle ACLR compared with an intraoperative image-free navigation system., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of 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 © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: Indirect calorimetry (IC) is the only way to measure in real time energy expenditure (EE) and to optimize nutrition support in acutely and chronically ill patients. Unfortunately, most of the commercially available indirect calorimeters are rather complex to use, expensive and poorly accurate and precise. Therefore, an innovative device (Q-NRG®, COSMED, Rome, Italy) that matches clinicians' needs has been developed as part of the multicenter ICALIC study supported by the two academic societies ESPEN and ESICM. The aim of this study was to evaluate the accuracy and intra- and inter-unit precision of this new device in canopy dilution mode in vitro and in spontaneously breathing adults., Methods: Accuracy and precision of oxygen consumption (VO 2 ) and carbon dioxide production (VCO 2 ) measurements were evaluated in vitro and in 15 spontaneously breathing healthy adults by interchanging three Q-NRG® units in a random order. In vitro validation was performed by gas exchange simulation using high-precision gas mixture and mass flow controller. Accuracy was calculated as error of measured values against expected ones based on volume of gas infused. Respiratory coefficient (RQ) accuracy was furthermore assessed using the ethanol-burning test. To evaluate the intra- and inter-unit precisions, the coefficient of variation (CV% = SD/Mean*100) was calculated, respectively, from the mean ± SD or the mean ± SD of the three mean values of VO 2 , VCO 2 , RQ and EE measured by each Q-NRG® units. In vivo accuracy measurement of the Q-NRG® was assessed by simultaneous comparison with mass spectrometry (MS) gas analysis, using Bland-Altman plot, Pearson correlation and paired t-test (significance level of p = 0.05)., Results: In vitro evaluation of the Q-NRG® accuracy showed measurement errors <1% for VO 2 , VCO 2 and EE and <1.5% for RQ. Evaluation of the intra- and inter-unit precision showed CV% ≤1% for VO 2 and EE and CV% ≤1.5% for VCO 2 and RQ measurements, except for one Q-NRG® unit where CV% was 2.3% for VO 2 and 3% for RQ. Very good inter-unit precision was confirmed in vivo with CV% equal to 2.4%, 3%, 2.8% and 2.3% for VO 2 , VCCO 2 , RQ and EE, respectively. Comparison with MS showed correlation of 0.997, 0.987, 0.913 and 0.997 for VO 2 , VCO 2 , RQ and EE respectively (p ≤ 0.05). Mean deviation of paired differences was 1.6 ± 1.4% for VO 2 , -1.5 ± 2.5% for VCO 2 , -3.1 ± 2.6% for RQ and 0.9 ± 1.4% for EE., Conclusion: Both in vitro and in vivo measurements of VO 2 , VCO 2 , RQ and EE on three Q-NRG® units showed minimal differences compared to expected values and MS and very low intra- and inter-unit variability. These results confirm the very good accuracy and precision of the Q-NRG® indirect calorimeter in canopy dilution mode in spontaneously breathing adults., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The tibial bony attachments of the anterior cruciate ligament (ACL) and the anterolateral meniscal root (ALMR) are very close, and drilling the tibial tunnel in ACL reconstruction may damage the ALMR attachment. This study investigated the relationship between the tibial attachment of the ACL and ALMR using high-resolution 3-T magnetic resonance imaging (MRI)., Methods: Twenty healthy subjects (35.8 ± 13.0 years) had 20 knees scanned using high resolution 3-T MRI. The tibial bony attachments of ACL, ALMR, and the tibia were segmented and three-dimensional models were created. The shape, area, and location of each attachment were evaluated using this model., Results: The ACL tibial attachment was elliptical in nine knees (45%), C-shaped in nine knees (45%) and triangle in two knees (10%). The mean values of the ACL vs ALMR tibial attachments were as follows: area, 106.2 ± 21.3 vs 56.2 ± 21.3 mm 2 ; length, 16.8 ± 2.0 vs 11.0 ± 1.8 mm; and width, 6.9 ± 1.3 vs 6.6 ± 1.0 mm. The location of the ACL vs ALMR attachment centres was 46.5 ± 1.7% vs 56.5 ± 1.9% in the medial-lateral direction and 36.3 ± 3.6% vs 36.7 ± 3.5% in the anterior-posterior direction. The distance between the ACL and ALMR centres was 8.1 ± 1.3 mm., Conclusions: ACL and ALMR tibial attachments were individually distinguished using high resolution 3-T MRI. The short distance between both centres of the attachments may suggest that ALMR can be damaged when the tibial tunnel is drilled in ACL reconstruction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background/objective: We compared the surgery data of the department of otorhinolaryngology of the university hospitals in Japan and Thailand to make each feature and the differences of both otorhinolaryngology surgeries clear. There are some medical meetings and congresses between Japan and Thailand, but so far it has not reported about the comparison of surgery data., Methods: Retrospectively, we analyzed the surgical statistics of department of otorhinolaryngology of Nihon University Itabashi Hospital (Japan) and Thammasat University Hospital (Thailand) between 2013 and 2014., Results: In Japan, there were many surgeries involving the middle ear and paranasal sinuses whereas in Thailand, tracheotomy and tonsillectomy were more frequently performed. Statistical analysis of the surgical data revealed specific tendencies in the nature of the operations performed at each university., Conclusion: This study revealed that there are rather differences between two hospitals' surgeries features. It was thought that it would be beneficial to both institutions to gain a deeper understanding of the areas of expertise of each university in order to foster an environment conducive to increasing future international collaborations., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Erythropoietin has been thought to be secreted to plasma soon after the production because of the difficulty of Western blot analysis and immunohistochemistry. We established the new methods of Western blot analysis and immunohistochemistry. Using the new methods, we investigated the effects of aldosterone and fludrocortisone, an analogue of aldosterone on erythropoietin mRNA and protein production by the kidneys. Aldosterone stimulated Epo and HIF2α mRNA expressions in tubule suspensions and microdissected medullary thick ascending limbs and outer medullary collecting ducts. Western blot analysis showed a recombinant erythropoietin at 34-45 kDa and kidney erythropoietin at 36-40 and 42 kDa, both of which shifted to 22 kDa by deglycosylation. Erythropoietin protein expression was observed in the nephrons but not in the interstitial cells in control condition. Fludrocortisone stimulated erythropoietin mRNA and protein expressions in the distal nephrons, particularly in the intercalated cells of the collecting ducts. These data show that erythropoietin is produced by the nephrons by the regulation of renin-angiotensin-aldosterone system and not by the renal interstitial cells in control condition., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The ductus arteriosus (DA), an essential fetal shunt between the pulmonary trunk and the descending aorta, changes its structure during development. Our previous studies have demonstrated that prostaglandin E 2 (PGE 2 )-EP4 signaling promotes intimal cushion formation (ICF) by activating the migration of DA smooth muscle cells via the secretion of hyaluronan. We hypothesized that, in addition to hyaluronan, PGE 2 may secrete other proteins that also regulate vascular remodeling in the DA. In order to detect PGE 2 stimulation-secreted proteins, we found that CCN3 protein was increased in the culture supernatant in the presence of PGE 2 in a dose-dependent manner by nano-flow liquid chromatography coupled with tandem mass spectrometry analysis and enzyme-linked immunosorbent assay. Quantitative RT-PCR analysis revealed that PGE 2 stimulation tended to increase the expression levels of CCN3 mRNA in DA smooth muscle cells. Immunohistochemical analysis revealed that CCN3 was highly localized in the entire smooth muscle layers and the endothelium of the DA. Furthermore, exogenous CCN3 inhibited PGE 2 -induced ICF in the ex vivo DA tissues. These results suggest that CCN3 is a secreted protein of the DA smooth muscle cells induced by PGE 2 to suppress ICF of the DA. The present study indicates that CCN3 could be a novel negative regulator of ICF in the DA to fine-tune the PGE 2 -mediated DA remodeling., (Copyright © 2018 Elsevier Inc. All rights reserved.)

There is an increasing need for assessing aquatic ecosystems that are globally endangered. Since aquatic ecosystems are complex, integrated consideration of multiple factors utilizing omics technologies can help us better understand aquatic ecosystems. An integrated strategy linking three analytical (machine learning, factor mapping, and forecast-error-variance decomposition) approaches for extracting the features of surface water from datasets comprising ions, metabolites, and microorganisms is proposed herein. The three developed approaches can be employed for diverse datasets of sample sizes and experimentally analyzed factors. The three approaches are applied to explore the features of bay water surrounding Odaiba, Tokyo, Japan, as a case study. Firstly, the machine learning approach separated 681 surface water samples within Japan into three clusters, categorizing Odaiba water into seawater with relatively low inorganic ions, including Mg, Ba, and B. Secondly, the factor mapping approach illustrated Odaiba water samples from the summer as rich in multiple amino acids and some other metabolites and poor in inorganic ions relative to other seasons based on their seasonal dynamics. Finally, forecast-error-variance decomposition using vector autoregressive models indicated that a type of microalgae (Raphidophyceae) grows in close correlation with alanine, succinic acid, and valine on filters and with isobutyric acid and 4-hydroxybenzoic acid in filtrate, Ba, and average wind speed. Our integrated strategy can be used to examine many biological, chemical, and environmental physical factors to analyze surface water., (Copyright © 2018. Published by Elsevier B.V.)

Background: Body weight loss (BWL) is frequently observed in gastric cancer patients who undergo gastrectomy for gastric cancer. The risk factors for severe BWL after gastrectomy remain unclear., Methods: The present study retrospectively examined patients who underwent curative gastrectomy for gastric cancer between January 2012 and June 2014 at Kanagawa Cancer Center. All patients received perioperative care based on the enhanced recovery after surgery protocol. The %BWL value was calculated based on the percentage of body weight at 1 month after surgery in comparison to the preoperative body weight. Severe BWL was defined as %BWL > 10%. The risk factors for severe BWL were determined by both univariate and multivariate logistic regression analyses., Results: There were 278 patients examined. The median age of the patients was 68 years. The operative procedures included total gastrectomy [n=97; open (n=61) and laparoscopic {n=36)] and distal gastrectomy (n=181). Surgical complications of grade ≥ 2 (as defined by the Clavien-Dindo classification) were observed in 37 patients, these included: pancreatic fistula (n=9), anastomotic leakage (n=5), and abdominal abscess (n=3). There were no cases of surgery-associated mortality. Both univariate and multivariate logistic analyses demonstrated that surgical complications, and total gastrectomy were significant risk factors for severe BWL., Conclusions: Surgical complications and total gastrectomy were identified as being significant risk factors for severe BWL in the 1 st month after gastrectomy. To maintain body weight after gastrectomy, physicians should pay careful attention to patients who undergo total gastrectomy and those who develop surgical complications., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Recently, digestive peptides prepared as a casein hydrolysate have been found to be an effective dispersant for the poorly water-soluble drug paclitaxel (Ptx). A major hydrophobic peptide in the digested peptides was identified as YQEPVLGPVRGPFPIIV (PepY) by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry with the "LIFT" technique. In the present study, three peptides PepY, VVVPPFLQPEVMGVSKV (PepV), and KFQSEEQQQTEDELQDK (PepK) were chemically synthesized by Fmoc solid-phase synthesis to compare their function as dispersants for Ptx. PepV and PepK are the most hydrophobic and hydrophilic peptides, respectively, in the sequence of β-casein, which are the same length as PepY (PepY, PepV, and PepK are abbreviated as Peps). The complex between Ptx and Peps (Ptx-Peps) was prepared by mixing an ethanol solution of Ptx and an aqueous solution of Peps, followed by lyophilization. The complex with PepV, which is estimated to be the most hydrophobic of the peptides, had the greatest ability to improve the water dispersibility of Ptx. The water dispersibility of the complexes between Ptx and PepY and PepV increased as the amount of the peptides increased, whereas PepK was not effective in enhancing the dispersibility of Ptx. Furthermore, a peptide mixture obtained from a casein hydrolysate [Pep (fraction A)] was more effective for the enhancement of Ptx dispersibility than the single peptide PepY. These results suggests that a variety of peptides in the casein hydrolysate contribute toward complexation with Ptx., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Depurination is accelerated by heat and reactive oxygen species under physiological conditions. We previously reported that polyamines are involved in mitigation of heat shock and oxidative stresses through stimulation of the synthesis of heat shock and antioxidant proteins. This time, we investigated whether polyamines are directly involved in protecting nucleic acids from thermal depurination induced by high temperature. The suppressing efficiencies of depurination of DNA by spermine, caldopentamine and caldohexamine in the presence of 1 mM Mg 2+ , were approximately 50%, 60% and 80%, respectively. Mg 2+ also protected nucleic acids against depurination but to a lesser degree than polyamines. Longer unusual polyamines were more effective at protecting DNA against depurination compared to standard polyamines. The tRNA depurination suppressing efficiencies of spermine, caldopentamine and caldohexamine in the presence of 1 mM Mg 2+ , were approximately 60%, 70% and 80%, respectively. Standard polyamines protected tRNA and ribosomes more effectively than DNA against thermal depurination. Branched polyamines such as mitsubishine and tetrakis(3-aminopropyl)ammonium also protected RNA more effectively than DNA against depurination. These results suggest that the suppressing effect of depurination of nucleic acids (DNA and RNA) depends on the types of polyamines: i.e. to maintain functional conformation of nucleic acids at high temperature, longer and branched polyamines play important roles in protecting nucleic acids from depurination compared to standard polyamines and Mg 2+ ., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Routine therapy of metabolic bone disorder (MBD) after gastrectomy for gastric cancer has not been established yet. We have reported that administering an active vitamin D3 agent to patients who had undergone gastrectomy for gastric cancer improved MBD. Recently, the usefulness of alendronate, an osteoclast inhibitor, has been reported for MBD. Here we report the effects of alendronate for MBD after gastrectomy for gastric cancer., Methods: Dual energy X-ray absorptiometry was performed consequently in 14 patients, who had been gastrectomized for gastric cancer and survived more than 5 years without recurrence, to evaluate the MBD and compared before and after treatment. The 14 patients were divided into two groups: in group VD3, 1 μg/d of alfacalcidol, an active vitamin D3 agent, was administered; and in group ALN, 5 mg/d or 35 mg/wk of alendronate or both alfacalcidol and alendronate were administered. These drugs had been administered to the patients for > 2 years, and the patients were followed up., Results: After 12 months, dual energy X-ray absorptiometry revealed that bone mineral density and T score were significantly increased in group ALN. Changes in serum bone-specific alkaline phosphatase after 24 months were -9.1 μg/L in the ALN group and 3.75 μg/L in the VD3 group, showing a significant difference (p = 0.02). No serious adverse events were observed in either group., Conclusion: These results showed the usefulness of alendronate and alendronate+activated vitamin D3 combination therapy, suggesting that these treatments might prevent postgastrectomic MBD., (Copyright © 2016. Published by Elsevier Taiwan.)

Background & Aims: This review aims to clarify the use of indirect calorimetry (IC) in nutritional therapy for critically ill and other patient populations. It features a comprehensive overview of the technical concepts, the practical application and current developments of IC., Methods: Pubmed-referenced publications were analyzed to generate an overview about the basic knowledge of IC, to describe advantages and disadvantages of the current technology, to clarify technical issues and provide pragmatic solutions for clinical practice and metabolic research. The International Multicentric Study Group for Indirect Calorimetry (ICALIC) has generated this position paper., Results: IC can be performed in in- and out-patients, including those in the intensive care unit, to measure energy expenditure (EE). Optimal nutritional therapy, defined as energy prescription based on measured EE by IC has been associated with better clinical outcome. Equations based on simple anthropometric measurements to predict EE are inaccurate when applied to individual patients. An ongoing international academic initiative to develop a new indirect calorimeter aims at providing innovative and affordable technical solutions for many of the current limitations of IC., Conclusion: Indirect calorimetry is a tool of paramount importance, necessary to optimize the nutrition therapy of patients with various pathologies and conditions. Recent technical developments allow broader use of IC for in- and out-patients., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Optimal nutritional care for intensive care unit (ICU) patients requires precise determination of energy expenditure (EE) to avoid deleterious under- or overfeeding. The reference method, indirect calorimetry (IC), is rarely accessible and inconstantly feasible. Various equations for predicting EE based on body weight (BW) are available. This study aims at determining the best prediction strategy unless IC is available., Methods: Mechanically ventilated patients staying ≥72 h in the ICU were included, except those with contraindications for IC measurements. IC and BW measurements were routinely performed. EE was predicted by the ESPEN formula and other predictive equations using BW (i.e. anamnestic (AN), measured (MES), adjusted for cumulated water balance (ADJ), calculated for a body mass index (BMI) of 22.5). Comparisons were made using Pearson correlation and Bland & Altman plots., Results: 85 patients (57 ± 19 y, 61 men, SAPS II 43 ± 16) were included. Correlations between IC and predicted EE using the ESPEN formula with different BW (BW AN , BW MES , BW ADJ , and BW BMI22.5 ) were 0.44, 0.40, 0.36, and 0.47, respectively. Bland & Altman plots showed wide and inconsistent variations. Predictive equations including body temperature and minute ventilation showed the best correlations, but when using various BWs, differences in predicted EE were observed., Conclusion: No EE predictive equation, regardless of the BW used, gives statistically identical results to IC. If IC cannot be performed, predictive equations including minute ventilation and body temperature should be preferred. BW has a significant impact on estimated EE and the use of measured BW MES or BW BMI 22.5 is associated with the best EE prediction. Clinical trial registration number on ClinicalTrial.gov: NCT02552446. Ethical committee number: CE-14-070., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: There have been a number of studies exploring treatments for psychogenic non-epileptic seizure (PNES) but largely neglecting the sizable subgroup of patients with intellectual disability (ID). In the present study, we attempted to demonstrate effects and preferred modes of therapeutic intervention in PNES patients with ID being treated at a Japanese municipal center with a short referral chain., Methods: We examined 46 PNES patients with ID (ID group) and 106 PNES patients without ID (non-ID group) retrospectively in case charts. In addition to examining basic demographic and clinical data, effects of different therapeutic intervention were examined as a function of decrease or disappearance of PNES attacks in the ID group., Results: Age at the first visit as well as PNES onset was younger in the ID than in the non-ID group (t=2.651, p=0.009; t=3.528, p=0.001, respectively). PNES-free ratio at the last visit tended to be higher in the non-ID group (chi square=3.455; p=0.063). Psychosis was more often encountered in the ID group (chi square=13.443; p=0.001). Although cognitive therapy and pharmaco-therapeutic approaches were quite similarly distributed in both groups, environmental adjustment was often introduced in the ID group (44%) as compared to the non-ID group (15%) (chi square=14.299; p=0.001). Brief weekly visit service is also more often utilized by the patients with ID (54%) than by those without ID (35%) (chi square=5.021, p=0.025)., Conclusions: Optimal treatment approaches in this sizable patient subgroup should be the subject of future prospective studies., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to investigate the relationship between psychological competitive ability and the incidence of noncontact ACL injuries among high school female athletes., Methods: A three-year prospective cohort study was conducted using 300 15-year-old high school female athletes with no previous injuries or symptoms in their lower limbs (106 handball players and 194 basketball players). At baseline, their psychological competitive abilities were assessed using a self-administered questionnaire-the Diagnostic Inventory of Psychological Competitive Ability (DIPCA.3). After the baseline examination was performed at high school entry, all players were prospectively followed for 36months to document any subsequent incidence of ACL injury, according to their coaches. An unpaired t-test with Welch's correction was performed to compare the differences in the psychological competitive abilities between the injured and uninjured players., Results: Of the 300 players, 25 (8.3%) experienced a noncontact ACL injury during the three-year observation period. The injured players had significantly higher total DIPCA.3 scores for psychological competitive ability than the uninjured players (169.9±18.8 vs. 159.2±21.6, P=.036). Additionally, the injured players had significantly higher scores than the uninjured players in the following categories: aggressiveness, volition for self-realization, volition for winning, judgment, and cooperation. However, no significant differences were observed in patience, self-control, ability to relax, concentration, confidence, decision, and predictive ability., Conclusions: High psychological competitive ability was associated with the incidence of noncontact ACL injuries in high school female athletes., Level of Evidence: Level II (prospective cohort study)., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background & Aims: We hypothesize that an optimal and simultaneous provision of energy and protein is favorable to clinical outcome of the critically ill patients., Methods: We conducted a review of the literature, obtained via electronic databases and focused on the metabolic alterations during critical illness, the estimation of energy and protein requirements, as well as the impact of their administration., Results: Critically ill patients undergo severe metabolic stress during which time a great amount of energy and protein is utilized in a variety of reactions essential for survival. Energy provision for critically ill patients has drawn attention given its association with morbidity, survival and long-term recovery, but protein provision is not sufficiently taken into account as a critical component of nutrition support that influences clinical outcome. Measurement of energy expenditure is done by indirect calorimetry, but protein status cannot be measured with a bedside technology at present., Conclusions: Recent studies suggest the importance of optimal and combined provision of energy and protein to optimize clinical outcome. Clinical randomized controlled studies measuring energy and protein targets should confirm this hypothesis and therefore establish energy and protein as a power couple., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Tip-apex distance (TAD) is reported as a good predictor for cut-outs of lag screws and spiral blades in the treatment of intertrochanteric fractures, and surgeons are advised to strive for TAD within 20 mm. However, the femoral neck axis and the position of the lower limb in the lateral radiograph are not clearly defined and can lead to measurement errors. We propose a refined TAD by defining these factors. The objective of this study was to analyze the reliability of this refined TAD., Methods: The radiographs of 130 prospective cases with unstable trochanteric fractures were used for the analysis of the refined TAD. The refined TAD was independently measured by 2 raters with clinical experience of more than 10 years (rater 1, 2) and 2 raters with much less clinical experience (rater 3, 4) after they received a training about the new measurement method. Intraclass correlation coefficient (ICC [2,4]) was calculated to assess the interrater reliability., Results: The mean refined TADs were 18.2:18.4:18.2:18.2 mm for rater 1:2:3:4. There was a strong correlation among all four raters (ICC 0.998, (95% CI: 0.998, 0.999)., Conclusions: Regardless of the clinical experience of raters, the refined TAD is a reliable tool and can be used to develop new TAD recommendations for predicting failure of fixation. Future studies with larger samples are needed to evaluate the predictive value of the refined TAD., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

We have recently shown that loss of the regenerating gene (Reg) I causes susceptibility to nonsteroidal anti-inflammatory drug-induced gastrointestinal damage. However, the mechanism by which Reg I plays a protective role against this pathophysiological condition is unclear. Here, we investigated whether Reg I plays roles in the induction of tight junction proteins and mucosal barrier function in the small intestine. The small-intestinal permeability was evaluated in Reg I-deficient mice by FITC-dextran and transepithelial electrical resistance (TEER) assay. The effect of REG Iα on TEER, claudins expression, and intracellular signaling was examined using Caco2 cells in vitro. Small-intestinal expression of claudins 3 and 4 was investigated in Reg I-deficient mice in vivo. REG I deficiency significantly decreased the expression of claudin 3 in the small-intestinal epithelium. When mice were treated with indomethacin, the serum level of FITC-dextran in Reg I knockout mice was significantly higher than that in wild-type (WT) mice. The level of small-intestinal TEER was significantly decreased in Reg I knockout mice compared with WT mice under normal condition. REG Iα stimulation significantly enhanced the level of TEER in Caco2 cells. Treatment with REG Iα enhanced the expression of claudins 3 and 4 and promoted Sp1, Akt, and ERK phosphorylation in Caco2 cells, whereas these effects were attenuated by treatment with anti-REG Iα antibody. Reg I may play a role in the maintenance of mucosal barrier function by inducing tight junction proteins such as claudins 3 and 4., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Lung cancer is generally considered as a highly malignant cancer. A major challenge for the management of lung adenocarcinoma patients is to predict the clinical course of the disease after resection. We analyzed the different levels of phosphorylation of proteins in lung adenocarcinoma tissues between a poor prognosis (PP) group, in which six patients exhibited recurrence within five years after surgery, and a good prognosis (GP) group, in which seven patients did not exhibit recurrence within five years after surgery. We found that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2) [phospho-SSFA2(pS92)] was stimulated in the PP group. Using samples from a total of 46 patients, we investigated the utility of phospho-SSFA2(pS92) to discriminate patients of GP and PP groups, with multiple reaction monitoring (MRM) mass spectrometry. Consequently, we confirmed that the PP group had significantly elevated phospho-SSFA2(pS92) levels. Additionally, no expression of SSFA2 recognized in the normal lung tissues. From these results, we demonstrate that phospho-SSFA2 (pS92) is related to the prognosis of early resected lung adenocarcinomas. Therefore, we suggest that phosphorylation of this protein indicates its role as a potential biomarker and new therapeutic target., Biological Significance: Lung adenocarcinoma patients often experience a high rate of recurrence after surgery. It is important to discover biomarkers for prognostic prediction and therapeutic targets for treatment of early-stage lung adenocarcinoma. In this study, using tissue samples obtained from patients with lung adenocarcinoma that had been stored for five years at -80°C, we identified 13 unique phosphorylated peptides, which were differentially expressed between poor and good prognosis groups. We confirmed that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2)[phospho-SSFA2 (pS92)], was related to poor prognosis. Our study demonstrates that prognostic prediction of early-stage lung adenocarcinoma is possible, and suggests new therapeutic targets for its treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Effective communication between pharmacists and patients is a crucial factor in ensuring that medications are used properly. However, few studies have examined the contents of actual on-site communications between pharmacists and patients., Objective: To identify the characteristics of and problems with routine communications between pharmacists and patients using the Roter Method of Interaction Process Analysis System (RIAS)., Methods: Conversations between pharmacists and simulated patients (SPs) were recorded and transcribed. Using the RIAS technique, their utterances were classified into 42 categories, and these were further divided into 11 clusters, such as open- and closed-ended questions, and analyzed. Furthermore, the influence that the different scenarios performed by the pharmacists may have had on the structure of their communication was investigated. All of the transcripts were double-coded by two certified coders., Results: A total of 57 pharmacists took part in the study. The mean ratio of utterances made by SPs and pharmacists were 44% and 56%, respectively. The percentage of pharmacists' questions was more than double that of SPs' for both open- and closed-ended questions. In the influence that the different scenarios, the scenarios for patients with cancer was significantly higher ratio of utterances by the pharmacists., Conclusions: Pharmacists' communications tended to focus more on information-gathering activities that concentrated on closed-ended questions and frequent counseling, or directing utterances about the medication than on considering the patient's background. On the other hand, the pharmacists did communicate in ways that matched each patient's disease. This study identified the structure of pharmacists' on-site communications, and revealed the associated characteristics and problems., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The anterolateral ligament (ALL) functions as a stabilizer in the internal rotation of the knee. Previous studies have reported the ALL can be identified using magnetic resonance imaging (MRI); however, there are no reports on using ultrasonography (US) for this purpose. Real-time virtual sonography (RVS) uses magnetic navigation and computer software for the synchronized display of real-time US and multiplanar reconstruction MRI images. This study investigated the ability of using US with RVS to evaluate the ALL., Methods: Nine healthy subjects were enrolled. The Digital Imaging Communications in Medicine MRI dataset was loaded into the Hitachi Aloka Preirus, and US images were displayed on the same monitor. When the ALL was identified using MRI, the monitor was frozen to evaluate the ALL. The ALL was divided into the femoral, meniscal, and tibial portions. The portions and thickness of the ALLs and the lateral inferior genicular artery (LIGA), a landmark for the ALL, were evaluated., Results: All portions of the ALL could be identified using MRI. Using US, the tibial portion of the ALL was detected in all subjects and the femoral portion was detected in seven subjects; however, the meniscal portions could not be identified. The average ALL thickness as measured by US was 1.3±0.1 mm and the LIGA was identified in all cases., Conclusions: Most portions of the ALL can be identified using US. As most ALL injuries occur at the femoral or tibial portion, US may be useful as a diagnostic tool for ALL injury., Level of Evidence: 4., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: This study aimed to present a new technique for anatomical single bundle anterior cruciate ligament (ACL) reconstruction. We developed an original rounded rectangular dilator set to create rounded rectangular femoral tunnels. This technique can increase the femoral tunnel size without roof impingement, and has the potential to reduce the graft failure rate. We investigated the tunnel position and the incidence of intraoperative complications., Method: The presented technique is anatomical single bundle ACL reconstruction using a semitendinosus graft (with or without the gracilis tendon). The tunnel was drilled via an additional medial portal. Rounded rectangular tunnels were created using a special dilator. Tibial tunnels were created using conventional rounded tunnels. Fixation was achieved using a suspensory device on the femoral side and a plate and screw on the tibial side., Patients: Fifty patients underwent this surgery, and intraoperative complications were investigated. The femoral tunnel positions were documented postoperatively from computed tomography scans using the quadrant method. The tibial tunnel positions (anterior-to-posterior, medial-to-lateral) were documented using intraoperative X-ray scans., Results: Only one patient had a partial posterior tunnel wall blowout. The femoral tunnel length varied between 30 and 40mm (mean, 34.9±3.3mm). All femoral and tibial tunnels were located within the area of the anatomical ACL insertions., Conclusion: We did not experience any serious intraoperative complications during anatomical single bundle ACL reconstruction using a rounded rectangle dilator, and the resulting locations of the femoral and tibial tunnels were within the anatomical ACL footprint., Level of Evidence: Level IV., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Lower-extremity muscle weakness in athletes after lower limb trauma or surgery can hinder their return to sports, and the associated muscle atrophy may lead to deterioration in performance after returning to sports. Recently, belt electrode skeletal muscle electrical stimulation (B-SES) which can contract all the lower limb skeletal muscles simultaneously was developed. However, no study has evaluated skeletal muscle activity with B-SES. Since only superficial muscles as well as a limited number of muscles can be investigated using electromyography, we investigated whether positron emission tomography (PET) can evaluate the activity of all the skeletal muscles in the body simultaneously. The purpose of this study was to evaluate the effectiveness of the B-SES system using PET., Methods: Twelve healthy males (mean age, 24.3 years) were divided into two groups. The subjects in the control group remained in a sitting position for 10 min, and [(18)F] fluorodeoxyglucose (FDG) was intravenously injected. In the exercise group, subjects exercised using the B-SES system for 20 min daily for three consecutive days as a pre-test exercise. On the measurement day, they exercised for 10 min, received an injection of FDG, and exercised for another 10 min. PET-computed tomography images were obtained in each group 60 min after the FDG injection. Regions of interest were drawn in each lower-extremity muscle. We compared each skeletal muscle metabolism using the standardized uptake value., Results: In the exercise group, FDG accumulation in the gluteus maximus, gluteus medius, gluteus minimus, quadriceps femoris, sartorius, and hamstrings was significantly higher than the muscles in the control (P < 0.05)., Conclusion: Exercise with B-SES increased the skeletal muscle activity of the gluteal muscles as well as the most lower-extremity muscles simultaneously., (Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

The complex between paclitaxel (Ptx) and a peptide mixture (Pep) was prepared to enhance of the water-dispersibility of Ptx. Pep was prepared by enzymatic hydrolysis of casein, followed by fractionation using ammonium sulfate precipitation and ultrafiltration. The Ptx and Pep complex (Ptx-Pep) was prepared by mixing an ethanol solution of Ptx and an aqueous solution of Pep followed by lyophilization. The water dispersibility test of Ptx-Pep prepared using different fractions of Pep demonstrated that a fraction (Pep-A), containing relatively hydrophobic peptides with high molecular weights, was effective in enhancing the water dispersibility of Ptx. The sequences of the major peptides in Pep-A were identified by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry with "LIFT" technique. The water dispersibility of the complex between Ptx and Pep-A (Ptx-Pep-A) was independent of pH, even though it is positively or negatively charged under strongly acidic and neutral conditions. As the particle size of Ptx-Pep-A in aqueous media was 147-215 nm, Ptx-Pep-A was present as a hydrocolloidal material in aqueous media., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The prognostic impact of worsening renal function (WRF) in acute coronary syndrome (ACS) patients is not fully understood in Japanese clinical practice, and clinical implication of persistent versus transient WRF in ACS patients is also unclear., Methods: With a single hospital-based cohort in the Shinken database 2004-2012 (n=19,994), we followed 604 ACS patients who underwent percutaneous coronary intervention (PCI). WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value. Persistent WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value and maintained until discharge, whereas transient WRF was defined as that WRF resolved at hospital discharge., Results: WRF occurred in 78 patients (13%), persistent WRF 35 patients (6%) and transient WRF 43 patients (7%). WRF patients were older and had a higher prevalence of chronic kidney disease, history of myocardial infarction (MI), and ST elevation MI. WRF was associated with elevated inflammatory markers and reduced left ventricular (LV) ejection fraction in acute, chronic phase. Incidence of all-cause death and major adverse cardiac events (MACE: all-cause death, MI, and target lesion revascularization) was significantly higher in patients with WRF. Moreover, in the WRF group, incidences of all-cause death and MACE were higher in patients with persistent WRF than those with transient WRF. A multivariate analysis showed that as well as older age, female gender, and intubation, WRF was an independent determinant of the all-cause death in ACS patients who underwent PCI., Conclusions: In conclusion, WRF might have a prognostic impact among Japanese ACS patients who underwent PCI in association with enhanced inflammatory response and LV remodeling. Persistent WRF might portend increased events, while transient WRF might have association with favorable outcomes compared with persistent WRF., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aim of this work was to analyse the suitability of mesenchymal stem cell isolation by FICOLL density centrifugation and the closed bone marrow aspirate concentrate (BMAC) system for sinus augmentation with bovine bone mineral (BBM) in the sheep model., Methods: 16 sheep underwent sinus augmentation with BBM and MSCs; they were divided between two groups with survival points of 8 and 16 weeks. For the FICOLL control arm three, and for the BMAC test arm, five augmentations were performed for each time point. The derived cell numbers were counted; a colony forming unit (CFU) assay was performed; the pluripotency of the MSCs was proved; histological and histomorphometrical analysis were performed., Results: The approach of using BBM and MSCs in combination with fibrin adhesive was sufficient for new bone formation as the FICOLL experiment indicated. However, due to significantly lower cell numbers isolated using the BMAC in sheep, less new bone was formed in the test arm., Conclusions: The BMAC system is well suited for human MSC isolation but it needs to be optimized to fit sheep cell characteristics if it is to be used in this animal model., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Affinity extraction based on the interaction between a target molecule and a specific affinity ligand offers a novel separation system for biomolecules in an aqueous two-phase system, however, most of affinity ligands are expensive. In the present study, metal affinity extraction of histidine (His) derivatives using a complex between Cu(II) and a commercially available chelating ligand was studied in a poly(ethylene glycol) (PEG)/Li2SO4 ATPS. Alizarin complexone (3-[N,N-bis(carboxymethyl)amino methyl]-1,2-dihydroxy anthraquinone, AC) was selected as the chelating ligand because of the good extractability of Cu(II) into the upper PEG-rich phase. On the basis of coordinate bonding with Cu(II), the extraction of His in the presence of the Cu(II)-AC complex under neutral condition was 73%, which was much higher than that under Cu(II) free condition (13%). Among a series of divalent transition metal ions (Cu(II), Ni(II), Co(II), and Zn(II)), Cu(II) was the most effective for the extraction of His. Derivatives of His were selectively extracted in the presence of many other amino acids because of the specificity of the interaction between Cu(II) and imidazole group of His. Extracted His was quantitatively stripped from the Cu(II)-AC complex using competitive complexation with agents such as iminodiacetic acid and imidazole., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Wiskott-Aldrich syndrome protein (WASP) is an adaptor molecule in immune cells. Recently, we showed that the WASP N-terminal domain interacted with the SH3 domain of Bruton's tyrosine kinase (Btk), and that the complex formed by WASP and Btk was important for TLR2 and TLR4 signaling in macrophages. Several other studies have shown that Btk played important roles in modulating innate immune responses through TLRs in immune cells. Here, we evaluated the significance of the interaction between WASP and Btk in TLR3, TLR7, and TLR9 signaling. We established bone marrow-derived macrophage cell lines from transgenic (Tg) mice that expressed intracellular antibodies (intrabodies) that specifically targeted the WASP N-terminal domain. One intrabody comprised the single-chain variable fragment and the other comprised the light-chain variable region single domain of an anti-WASP N-terminal monoclonal antibody. Both intrabodies inhibited the specific interaction between WASP and Btk, which impaired the expression of TNF-α, IL-6, and IL-1β in response to TLR3, TLR7, or TLR9 stimulation. Furthermore, the intrabodies inhibited the phosphorylation of both nuclear factor (NF)-κB and WASP in response to TLR3, TLR7, or TLR9 stimulation, in the Tg bone marrow-derived macrophages. These results suggested that WASP plays important roles in TLR3, TLR7, and TLR9 signaling by associating with Btk in macrophages., (Copyright © 2015 Elsevier Inc. All rights reserved.)