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TP0446131, developed as an antidepressant agent, was found to cause lenticular opacity in a 13-week repeated-dose study in dogs. Histopathologically, the lenticular opacity was observed as a degeneration of the lens fibers, characterized by irregularity in the ordered arrangement of the fibers which is necessary to maintain the transparency of the lens, and was considered to manifest clinically as cataract. To evaluate the development mechanism of the lenticular opacity, the chemical constituents of the lens, which is known to be associated with the development of cataract, were examined. The results of liquid chromatography-tandem mass spectrometry analysis revealed an increase in the amplitudes of 3 unknown peaks in a dose- and time-dependent manner in the lens, with no remarkable changes in the other chemical components tested. In addition, the content of cholesterol, alterations of which have been reported to be associated with cataract, remained unchanged. The mass spectral data and chromatographic behavior of the 3 peaks indicated that these peaks corresponded to sterol-related substances, and that one of them was 7-dehydrocholesterol, a precursor of cholesterol biosynthesis. This finding suggested that TP0446131 exerts some effects on the cholesterol biosynthesis pathway, which could be involved in the development of the cataracts. Furthermore, increases in the levels of these sterol-related substances were also detected in the serum, and were, in fact, noted prior to the onset of the cataract, suggesting the possibility that these substances in the serum could be used as potential safety biomarkers for predicting the onset of cataract induced by TP0446131. [ABSTRACT FROM AUTHOR]

In the present study, the free-energy landscape of a hydrated alanine dipeptide has been studied by the 3D-RISM theory. We calculate the hydration free energy as a function of dihedral angles φ and ψ using both the 3D-RISM theory and the umbrella sampling method. The 3D-RISM results are found to be in good agreement with those by the umbrella sampling calculations, demonstrating the reliability of the integral equation theory applied to bimolecular systems. [ABSTRACT FROM AUTHOR]

Ordinary lipoma is cytogenetically characterized by structural rearrangements, particularly translocations, of 12q13-15. By contrast, atypical lipomatous tumors exhibit supernumerary ring or giant marker chromosomes that are composed mainly of amplified material from the 12q13-15 chromosome segment. The present study describes the cytogenetic and molecular cytogenetic findings from a lipomatous tumor with minimal nuclear atypia that was identified in a 49-year-old female patient. Magnetic resonance imaging of the right shoulder revealed a 13-cm fatty mass in the subcutaneous layer that possessed only pencil-line septa. Contrast-enhanced fat-suppressed T1-weighted images demonstrated faint enhancement. A marginal excision was performed. Histologically, the tumor was composed of lobules that consisted of mature adipocytes separated by thin fibrous septa. There was minimal nuclear atypia in certain cells, and a small number of binucleated cells were also observed within the tumor. Immunohistochemically, the tumor cells did not reveal the expression of murine double-minute 2 (MDM2). Cytogenetic analysis revealed a complex karyotype with several numerical and structural alterations, including 12q rearrangements. Spectral karyotyping demonstrated a duplication of chromosome segment 12q13-15. Interphase fluorescence in situ hybridization analysis revealed no MDM2 gene amplification. The present case indicates that duplication of 12q may be associated with minimal nuclear atypia in a subset of lipomatous tumors. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective study. Purpose: To examine the effectiveness of using an electrodiagnostic technique as a new approach in the clinical diagnosis of extraforaminal stenosis at L5-S1. Overview of Literature: We introduced a new effective approach to the diagnosis of extraforaminal stenosis at the lumbosacral junction using the existing electrophysiological evaluation technique. Methods: A consecutive series of 124 patients with fifth lumbar radiculopathy were enrolled, comprising a group of 74 patients with spinal canal stenosis and a second group of 50 patients with extraforaminal stenosis at L5-S1. The technique involved inserting a pair of needle electrodes into the foraminal exit zone of the fifth lumbar spinal nerves, which were used to provide electrical stimulation. The compound muscle action potentials from each of the tibialis anterior muscles were recorded. Results: The distal motor latency (DML) of the potentials ranged from 11.2 to 24.6 milliseconds in patients with extraforaminal stenosis. In contrast, the DML in patients with spinal canal stenosis ranged from 10.0 to 17.2 milliseconds. After comparing the DML of each of the 2 groups and at the same time comparing the differences in DML between the affected and unaffected side of each patient, we concluded there were statistically significant differences (p <0.01) between the 2 groups. Using receiver operating characteristic curve analysis, the cutoff values were calculated to be 15.2 milliseconds and 1.1 milliseconds, respectively. Conclusions: This approach using a means of DML measurement enables us to identify and localize lesions, which offers an advantage in diagnosing extraforaminal stenosis at L5-S1. [ABSTRACT FROM AUTHOR]

Abstract Background: Escherichia coli RuvAB promotes branch migration of Holliday junctions during recombination repair and homologous recombination. RuvB forms a hexameric ring through which duplex DNA passes and is translocated in an ATP-dependent manner. ATPase-deficient RuvB mutant K68A has a mutation in the Walker A motif and exerts a dominant-negative effect on in vivo repair of UV-induced DNA damage. In this study, we examined RuvAB-dependent branch migration in the presence of a mutant RuvB, K68A. Results: Mixing K68A with wild-type RuvB resulted in the formation of heterohexamers that showed unique properties of DNA binding, ATPase, and branch migration activities different from those of either wild-type or mutant homohexamers. RuvB heterohexamers inhibited branch migration and caused Holliday junctions to accumulate during RecA-mediated strand exchange. In the presence of RuvA, RuvB heterohexamers had Holliday junction-dependent ATPase activity, but did not promote branch migration. Conclusions: These results suggest that functional cooperation among the subunits in the hexamers is required for branch migration, but inclusion of inactive subunits is tolerated for ATP hydrolysis. Therefore, we propose that an essential ATP hydrolysis-dependent functional cooperation is induced in RuvB hexamer subunits during RuvAB-mediated branch migration. [ABSTRACT FROM AUTHOR]

A prospective multicenter observational cohort study. Objective. This study aimed to investigate the role of transcranial motor evoked potential (TcMEP) monitoring during traumatic spinal injury surgery, the timing of TcMEP alerts, and intervention strategies to avoid intraoperative neurological complications. Summary of Background Data. Intraoperative neuromonitoring, including TcMEP monitoring, is commonly used in high-risk spinal surgery to predict intraoperative spinal cord injury; however, little information is available on its use in traumatic spinal injury surgery. Methods. The TcMEP monitoring data of 350 consecutive patients who underwent traumatic spinal injury surgery (mean age, 69.3 y) between 2017 and 2021 were prospectively reviewed. In this study, a TcMEP amplitude reduction =70% was established as a TcMEP alert. A rescue case was defined as a case with the recovery of TcMEP amplitudes after certain procedures and without postoperative neurological complications. Results. Among the 350 patients who underwent traumatic spinal injury surgery (TcMEP derivation rate 94%), TcMEP monitoring revealed seven true-positive (TP) (2.0%), three rescues (0.9%; rescue rate 30%), 31 false-positive, one false-negative, and 287 true-negative cases, resulting in 88% sensitivity, 90% specificity, 18% positive predictive value, and 99% negative predictive value. The TP rate in patients with preoperative motor deficits was 2.9%, which was higher than that in patients without preoperative motor deficits (1.1%). The most common timing of TcMEP alerts was during decompression (40%). During decompression, suspension of surgery with intravenous steroid injection was ineffective (rescue rate, 0%), and additional decompression was effective. Conclusion. Given the low prevalence of neurological complications (2.3%) and the low positive predictive value (18.4%), single usage of TcMEP monitoring during traumatic spinal injury surgery is not recommended. Further efforts should be made to reduce FP alert rates through better interpretation of multimodal Intraoperative neuromonitorings and the incorporation of anesthesiology to improve the positive predictive value. [ABSTRACT FROM AUTHOR]

Study Design: Prospective multicenter observational study.Objective: To evaluate transcranial motor-evoked potentials (Tc-MEPs) baseline characteristics of lower limb muscles and to determine the accuracy of Tc-MEPs monitoring based on preoperative motor status in surgery for high-risk spinal disease.Summary Of Background Data: Neurological complications are potentially serious side effects in surgery for high-risk spine disease. Intraoperative spinal neuromonitoring (IONM) using Tc-MEPs waveforms can be used to identify neurologic deterioration, but cases with preoperative motor deficit tend to have poor waveform derivation.Methods: IONM was performed using Tc-MEPs for 949 patients in high-risk spinal surgery. A total of 4454 muscles in the lower extremities were chosen for monitoring. The baseline Tc-MEPs was recorded immediately after exposure of the spine. The derivation rate was defined as muscles detected/muscles prepared for monitoring. A preoperative neurological grade was assigned using the manual muscle test (MMT) score.Results: The 949 patients (mean age 52.5 ± 23.3 yrs, 409 males [43%]) had cervical, thoracic, thoracolumbar, and lumbar lesions at rates of 32%, 40%, 26%, and 13%, respectively. Preoperative severe motor deficit (MMT ≤3) was present in 105 patients (11%), and thoracic ossification of the posterior longitudinal ligament (OPLL) was the most common disease in these patients. There were 32 patients (3%) with no detectable waveform in any muscles, and these cases had mostly thoracic lesions. Baseline Tc-MEPs responses were obtained from 3653/4454 muscles (82%). Specificity was significantly lower in the severe motor deficit group. Distal muscles had a higher waveform derivation rate, and the abductor hallucis (AH) muscle had the highest derivation rate, including in cases with preoperative severe motor deficit.Conclusion: In high-risk spinal surgery, Tc-MEPs collected with multi-channel monitoring had significantly lower specificity in cases with preoperative severe motor deficit. Distal muscles had a higher waveform derivation rate and the AH muscle had the highest rate, regardless of the severity of motor deficit preoperatively.Level of Evidence: 3. [ABSTRACT FROM AUTHOR]

Calcifying aponeurotic fibroma (CAF) is a rare, locally aggressive fibroblastic lesion that occurs predominantly in the distal extremities of children and adolescents. In the present study, a case of pathologically proven CAF arising in the right little finger of a 69-year-old woman is presented. Physical examination revealed a firm, immobile, non-tender mass. Plain radiographs showed a faintly calcified soft tissue mass without bone involvement and computed tomography scans clearly demonstrated the presence of the lesion. Magnetic resonance imaging revealed that the lesion exhibited low to intermediate signal intensity on T1-weighted images and heterogeneous high signal intensity with small foci of low signal intensity on T2-weighted spectral presaturation with inversion recovery images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated intense heterogeneous enhancement throughout the mass. The patient underwent an excisional biopsy. Histologically, the tumor showed a biphasic pattern, composed of a moderately cellular fibromatosis-like component and irregular calcified areas with polygonal epithelioid cells. There has been no evidence of local recurrence four months following surgery. To the best of our knowledge, this case report describes the oldest patient with this condition. [ABSTRACT FROM AUTHOR]

The Mre11-Rad50-Nbs1 complex (MRN) is important for repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). The endonuclease activity of MRN is critical for resecting 5'-ended DNA strands at DSB ends, producing 3'-ended single-strand DNA, a prerequisite for HR. This endonuclease activity is stimulated by Ctp1, the Schizosaccharomyces pombe homolog of human CtIP. Here, with purified proteins, we show that Ctp1 phosphorylation stimulates MRN endonuclease activity by inducing the association of Ctp1 with Nbs1. The highly conserved extreme C terminus of Ctp1 is indispensable for MRN activation. Importantly, a polypeptide composed of the conserved 15 amino acids at the C terminus of Ctp1 (CT15) is sufficient to stimulate Mre11 endonuclease activity. Furthermore, the CT15 equivalent from CtIP can stimulate human MRE11 endonuclease activity, arguing for the generality of this stimulatory mechanism. Thus, we propose that Nbs1-mediated recruitment of CT15 plays a pivotal role in the activation of the Mre11 endonuclease by Ctp1/CtIP. [ABSTRACT FROM AUTHOR]

Study Design: Prospective, multicenter, observational study.Objective: The aim of this study was to investigate the efficacy of intervention after an alert in intraoperative neurophysiological monitoring (IONM) using transcranial motor-evoked potentials (Tc-MEPs) during surgery for thoracic ossification of the posterior longitudinal ligament (T-OPLL).Summary Of Background Data: T-OPLL is commonly treated with posterior decompression and fusion with instrumentation. IONM using Tc-MEPs during surgery reduces the risk of neurological complications.Methods: The subjects were 79 patients with a Tc-MEP alert during posterior decompression and fusion surgery for T-OPLL. Preoperative muscle strength (manual muscle testing [MMT]), waveform derivation rate at the start of surgery (baseline), intraoperative waveform changes; and postoperative motor paralysis were examined. A reduction in MMT score of ≥1 on the day after surgery was classified as worsened postoperative motor deficit. An alert was defined as a decrease in Tc-MEP waveform amplitude of ≥70% from baseline. Alerts were recorded at key times during surgery.Results: The patients (35 males, 44 females; age 54.6 years) had OPLL at T1-4 (n = 27, 34%), T5-8 (n = 50, 63%), and T9-12 (n = 16, 20%). The preoperative status included sensory deficit (n = 67, 85%), motor deficit (MMT ≤4) (n = 59, 75%), and nonambulatory (n = 26, 33%). At baseline, 76 cases (96%) had a detectable Tc-MEP waveform for at least one muscle, and the abductor hallucis had the highest rate of baseline waveform detection (n = 66, 84%). Tc-MEP alerts occurred during decompression (n = 47, 60%), exposure (n = 13, 16%), rodding (n = 5, 6%), pedicle screw insertion (n = 4, 5%), posture change (n = 4, 5%), dekyphosis (n = 2, 3%), and other procedures (n = 4, 5%). After intraoperative intervention, the rescue rate (no postoperative neurological deficit) was 57% (45/79), and rescue cases had a significantly better preoperative ambulatory status and a significantly higher baseline waveform derivation rate.Conclusion: These results show the efficacy of intraoperative intervention following a Tc-MEP alert for prevention of neurological deficit postoperatively.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Homologous recombination (HR) is essential for maintaining genome stability. Although Rad51 is the key protein that drives HR, multiple auxiliary factors interact with Rad51 to potentiate its activity. Here, we present an interdisciplinary characterization of the interactions between Rad51 and these factors. Through structural analysis, we identified an evolutionarily conserved acidic patch of Rad51. The neutralization of this patch completely abolished recombinational DNA repair due to defects in the recruitment of Rad51 to DNA damage sites. This acidic patch was found to be important for the interaction with Rad55-Rad57 and essential for the interaction with Rad52. Furthermore, biochemical reconstitutions demonstrated that neutralization of this acidic patch also impaired the interaction with Rad54, indicating that a single motif is important for the interaction with multiple auxiliary factors. We propose that this patch is a fundamental motif that facilitates interactions with auxiliary factors and is therefore essential for recombinational DNA repair. [ABSTRACT FROM AUTHOR]

Homologous recombination (HR) is a universal mechanism operating in somatic and germ-line cells, where it contributes to the maintenance of genome stability and ensures the faithful distribution of genetic material, respectively. The ability to identify and exchange the strands of two homologous DNA molecules lies at the heart of HR and is mediated by RecA-family recombinases. Dmc1 is a meiosis-specific RecA homolog in eukaryotes, playing a predominant role in meiotic HR. However, Dmc1 cannot function without its two major auxiliary factor complexes, Swi5-Sfr1 and Hop2-Mnd1. Through biochemical reconstitutions, we demonstrate that Swi5-Sfr1 and Hop2-Mnd1 make unique contributions to stimulate Dmc1-driven strand exchange in a synergistic manner. Mechanistically, Swi5-Sfr1 promotes establishment of the Dmc1 nucleoprotein filament, whereas Hop2-Mnd1 defines a critical, rate-limiting step in initiating strand exchange. Following execution of this function, we propose that Swi5-Sfr1 then promotes strand exchange with Hop2-Mnd1. Thus, our findings elucidate distinct yet complementary roles of two auxiliary factors in Dmc1-driven strand exchange, providing mechanistic insights into some of the most critical steps in meiotic HR. [ABSTRACT FROM AUTHOR]

Eukaryotic Rad51 protein is essential for homologous-recombination repair of DNA double-strand breaks. Rad51 recombinases first assemble onto single-stranded DNA to forma nucleoprotein filament, required for function in homology pairing and strand exchange. This filament assembly is the first regulation step in homologous recombination. Rad51 nucleation is kinetically slow, and several accessory factors have been identified to regulate this step. Swi5-Sfr1 (S5S1) stimulates Rad51-mediated homologous recombination by stabilizing Rad51 nucleoprotein filaments, but the mechanism of stabilization is unclear. We used single-molecule tethered particle motion experiments to show that mouse S5S1 (mS5S1) efficiently stimulates mouse RAD51 (mRAD51) nucleus formation and inhibits mRAD51 dissociation from filaments. We also used single-molecule fluorescence resonance energy transfer experiments to show that mS5S1 promotes stable nucleus formation by specifically preventing mRAD51 dissociation. This leads to a reduction of nucleation size from three mRAD51 to two mRAD51 molecules in the presence of mS5S1. Compared with mRAD51, fission yeast Rad51 (SpRad51) exhibits fast nucleation but quickly dissociates from the filament. SpS5S1 specifically reduces SpRad51 disassembly to maintain a stable filament. These results clearly demonstrate the conserved function of S5S1 by primarily stabilizing Rad51 on DNA, allowing both the formation of the stable nucleus and the maintenance of filament length. [ABSTRACT FROM AUTHOR]

Background. Catheter-associated urinary tract infection is a common and costly problem throughout the world. As limited data from Asia exist regarding the prevalence and appropriateness of urinary catheters in critically ill patients, we sought to assess both prevalence and appropriateness of urinary catheters in Japan. Methods. Using independent observers, we evaluated the prevalence and clinical necessity of indwelling urinary catheters in 7 Japanese intensive care units. Results. Data were collected on 1289 catheter-days and 1706 patient days in the 7 participating intensive care units between August 2015 and May 2016. Urinary catheter prevalence was 76% (range, 49%-94%). The observers deemed that only 54% of the catheters met an appropriate indication for use (range, 40%-74%). The most common appropriate indications for urinary catheter use were (1) the need for accurate input and output monitoring in critically ill patients; (2) perioperative use; and (3) prolonged immobilization. The use of monitoring accurate input and output in critically ill patients, however, may be overused as bedside nurses used this indication in 27% more patients than the objective observer deemed necessary. Conclusions. Urinary catheters were frequently used in the 7 participating Japanese intensive care units and almost half did not meet an appropriate indication for use. Overusing catheters for monitoring accurate input and output was especially notable. Multimodal interventions may be needed to limit inappropriate urinary catheter use. [ABSTRACT FROM AUTHOR]

Holliday junctions, four-stranded DNA structures formed during homologous recombination, are disentangled by resolvases that have been found in prokaryotes and eukaryotes but not in plant organelles. Here, we identify monokaryotic chloroplast 1 (MOC1) as a Holliday junction resolvase in chloroplasts by analyzing a green alga Chlamydomonas reinhardtii mutant defective in chloroplast nucleoid (DNA-protein complex) segregation. MOC1 is structurally similar to a bacterial Holliday junction resolvase, resistance to ultraviolet (Ruv) C, and genetically conserved among green plants. Reduced or no expression of MOC1 in Arabidopsis thaliana leads to growth defects and aberrant chloroplast nucleoid segregation. In vitro biochemical analysis and high-speed atomic force microscopic analysis revealed that A. thaliana MOC 1 (AtMOC1) binds and cleaves the core of Holliday junctions symmetrically. MOC1 may mediate chloroplast nucleoid segregation in green plants by resolving Holliday junctions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate fluid loading-induced changes in left ventricular end-diastolic volume (LVEDV) and stroke volume variability (SVV) in patients with end-stage renal disease (ESRD) using real-time three-dimensional transesophageal echocardiography and the Vigileo-FloTrac system.Patients and Methods: After obtaining ethics committee approval and informed consent, 28 patients undergoing peripheral vascular procedures were studied. Fourteen patients with ESRD on hemodialysis (HD) were assigned to the HD group and 14 patients without ESRD were assigned to the control group. Institutional standardized general anesthesia was provided in both groups. SVV was measured using the Vigileo-FloTrac system. Simultaneously, a full-volume three-dimensional transesophageal echocardiography dataset was acquired to measure LVEDV, left ventricular end-systolic volume, and left ventricular ejection fraction. Measurements were obtained before and after loading 500 mL hydroxyethyl starch over 30 minutes in both groups.Results: In the control group, intravenous colloid infusion was associated with a significant decrease in SVV (13.8%±2.6% to 6.5%±2.6%, P<0.001) and a significant increase in LVEDV (83.6±23.4 mL to 96.1±28.8 mL, P<0.001). While SVV significantly decreased after infusion in the HD group (16.2%±6.0% to 6.2%±2.8%, P<0.001), there was no significant change in LVEDV.Conclusion: Our preliminary data suggest that fluid responsiveness can be assessed not by LVEDV but also by SVV due to underlying cardiovascular pathophysiology in patients with ESRD. [ABSTRACT FROM AUTHOR]

Purpose: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease. Methods: Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM). Results: The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model. Conclusion: The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively. [ABSTRACT FROM AUTHOR]

The patella is a rare site for the development of primary tumors. This is the case report of a giant cell tumor (GCT) occurring in the patella in a 25-year-old woman. The patient presented with a 1-year history of occasional right anterior knee pain. The radiological characteristics suggested a benign condition. The intraoperative pathological diagnosis was GCT of the bone. The lesion was treated by radical curettage with adjuvant therapy comprising phenol and ethanol and injection of calcium phosphate cement. Histologically, the tumor consisted of round or spindle-shaped mononuclear cells admixed with numerous osteoclastic giant cells. The patient was asymptomatic and there was no evidence of local recurrence or distant metastasis 16 months after surgery. Although rare, patellar GCT may be included in the differential diagnosis of anterior knee pain and/or swelling, particularly in young adults. [ABSTRACT FROM AUTHOR]

Purpose. Hypoglossal nerve palsy after use of the laryngeal mask airway (LMA) is an exceptionally rare complication. We present the first case of unilateral hypoglossal nerve palsy after use of the LMA Supreme. Clinical Features. A healthy 67-year-old female was scheduled for a hallux valgus correction under general anesthesia combined with femoral and sciatic nerve blocks. A size 4 LMA Supreme was inserted successfully at the first attempt and the cuff was inflated with air at an intracuff pressure of 60 cmH2O using cuff pressure gauge. Anesthesia was maintained with oxygen, nitrous oxide (67%), and sevoflurane under spontaneous breathing. The surgery was uneventful and the duration of anesthesia was two hours. The LMA was removed as the patient woke and there were no immediate postoperative complications. The next morning, the patient complained of dysarthria and dysphasia. These symptoms were considered to be caused by the LMA compressing the nerve against the hyoid bone. Conservative treatment was chosen and the paralysis recovered completely after 5 months. Conclusion. Hypoglossal nerve injury may occur despite correct positioning of the LMA under the appropriate intracuff pressure. A follow-up period of at least 6 months should be taken into account for the recovery. [ABSTRACT FROM AUTHOR]

Theobjective of this study was to determine the point after sugammadex administration atwhich sufficient or insufficient dose could be determined, using first twitch height of train-of-four (T1 height) or train-of-four ratio (TOFR) as indicators. Groups A and B received 1mg/kg and 0.5mg/kg of sugammadex, respectively, as a first dose when the second twitch reappeared in train-of-four stimulation, and Groups C and Dreceived 1mg/kg and 0.5mg/kg of sugammadex, respectively, as the first dose at posttetanic counts 1-3. Five minutes after the first dose, an additional 1mg/kg of sugammadex was administered and changes in T1 height and TOFR were observed. Patients were divided into a recovered group and a partly recovered group, based on percentage changes in T1 height after additional dosing. T1 height and TOFR during the 5 min after first dose were then compared. In the recovered group, TOFR exceeded 90% in all patients at 3 min after sugammadex administration. In the partly recovered group, none of the patients had a TOFR above 90% at 3 min after sugammadex administration. An additional dose of sugammadex can be considered unnecessary if the train-of-four ratio is =90% at 3 min after sugammadex administration. This trial is registered with UMIN000007245. [ABSTRACT FROM AUTHOR]

Periosteal chondroma is a rare benign hyaline cartilage neoplasm that occurs most commonly in the metaphases of long tubular bones. We present a unique case of periosteal chondroma arising in the proximal phalanx of the left index finger in a 12-year old boy. Physical examination revealed a slightly protuberant, subcutaneous mass. Plain radiographs and computed tomography scans showed a periosteal lesion producing saucerization of the cortex and subjacent cortical sclerosis, without internal matrix calcification. On magnetic resonance imaging, the lesion exhibited intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated peripheral and septal enhancement. The patient underwent a marginal excision with curettage of the underlying bone cortex. Histological examination confirmed the diagnosis of periosteal chondroma. There has been no evidence of local recurrence eight months after surgery. Periosteal chondroma can protrude into the subcutaneous soft tissue causing a palpable mass. Recognition of the typical radiological features can lead to an accurate diagnosis of this rare condition. [ABSTRACT FROM AUTHOR]

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive and associated with poor prognosis. Basic research to develop new treatment regimens is critically needed. Methods: The effects of imatinib mesylate on MPNSTs were examined in six human MPNST cell lines and in a xenograft mouse model. Results: The results showed expression of platelet-derived growth factor receptor-β and suppression of its phosphorylation by imatinib mesylate in all six cell lines. Imatinib mesylate effectively suppressed MPNST cell growth in vitro at concentrations similar to those used clinically (1.46 - 4.6 μM) in three of six cell lines. Knockdown of PDGFR-β by transfection with a specific siRNA also caused significant reduction in cell proliferation in the sensitive cell lines, but not in the resistant cell lines. Furthermore, imatinib mesylate also significantly suppressed colony formation within soft agar and tumor growth in xenograft models using two of the three sensitive MPNST cell lines. There was excellent agreement between in vitro and in vivo sensitivity to imatinib mesylate, suggesting possible selection of imatinib-sensitive tumors by in vitro analysis. Conclusions: The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo. [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma is an aggressive type of neoplasm difficult to cure by conventional procedures. Because of the lack of reliable markers for assessing the prognosis, this retrospective study was designed to investigate the prognostic significance of MK-1 overexpression in human carcinoma of the gallbladder. Immunohistochemical staining using monoclonal antibody FU-MK-1 (MK-1 antigen) was performed on paraffin-embedded tissues from 63 patients who had undergone surgical resection for gallbladder carcinoma. Expression of MK-1 was found in 50 (79%) of 63 tumor samples. All 21 papillary and 12 of 13 well-differentiated tubular adenocarcinomas but only 1 of 8 poorly differentiated adenocarcinomas were positive for FU-MK-1. Multivariate analysis showed that only MK-1 expression was an independent prognostic marker (P = .0473), and Kaplan-Meier curves showed that MK-1 expression was significantly related to increased overall survival (P < .0001). These results suggest that MK-1 expression is a prognostic marker in gallbladder carcinoma. [ABSTRACT FROM AUTHOR]

The article presents the case of a female infant who suffered graft dysfunction after the Norwood operation. The patient was scheduled for an emergency right modified Blalock-Taussig shunt (MBTS). Venovenous extracorporeal membrane oxygenation (VV-ECMO) was also planned to avoid the risk of perioperative hypoxemia. After anesthetic induction, a bicaval dual-lumen catheter was placed in the right internal jugular vein under ultrasound guidance and VV-ECMO was implemented. [ABSTRACT FROM AUTHOR]