Pathological and Biological Significance of the Specific Glycan, TRA-1-60, on Aggressive Gastric Adenocarcinoma.

The glycans form a unique complex on the surface of cancer cells and play a pivotal role in tumor progression, impacting proliferation, invasion, and metastasis. TRA-1-60 is a glycan that was identified as a critical marker for the establishment of fully reprogrammed inducible pluripotent stem cells. Its expression has been detected in multiple cancer tissues, including embryonal carcinoma, prostate cancer, and pancreatic cancer, but the biological and pathological characterization of TRA-1-60-expressing tumor cells remains unclear within various types of malignancies. Here, we report the biological characteristics of TRA-1-60-expressing gastric cancer cells, especially those with its cell surface expression, and the therapeutic significance of targeting TRA-1-60. The cells with cell membrane expression of TRA-1-60 were mainly observed in the invasive area of patient gastric cancer tissues and correlated with advanced stages of the disease based on histopathological and clinicopathological analyses. In vitro analysis using a scirrhous gastric adenocarcinoma line, HSC-58, which highly expresses TRA-1-60 on its plasma membrane, revealed increased stress-resistant mechanisms, supported by the upregulation of glutathione synthetase and NCF-1 (p47phox) via lipid-ROS regulatory pathways, as detected by RNA-seq analysis followed by oxidative stress gene profiling. Our in vivo therapeutic study using the TRA-1-60-targeting antibody-drug conjugate, namely, Bstrongomab-conjugated monomethyl auristatin E, showed robust efficacy in a mouse model of peritoneal carcinomatosis induced by intraperitoneal xenograft of HSC-58, by markedly reducing massive tumor ascites. Thus, targeting the specific cell surface glycan, TRA-1-60, shows a significant therapeutic impact in advanced-stage gastric cancers.

Effects of maternal magnesium sulfate treatment on newborns.

BACKGROUND: Antenatal magnesium sulfate (MgSO4 ) has been used with mothers, but the influence of MgSO4 on the fetus is unclear. The purpose of this study is to determine whether longer antenatal MgSO4 exposure correlates with adverse effects in newborns. METHODS: The clinical data of 77 infants born to mothers treated with MgSO4 were collected. The infants were divided into two groups according to (1) the serum Mg concentration, (2) cumulative Mg dose, and (3) duration of antenatal maternal Mg treatment, respectively. RESULTS: The serum Mg level of the infants correlated with that of the mothers but not with the duration of Mg treatment or the cumulative dose of Mg. There were no significant differences in the infants' clinical variables according to either the duration of Mg treatment or the cumulative dose of Mg. By contrast, enteral feeding tolerance began at a significantly later age and the heart rate on admission was significantly lower in infants with a serum Mg level ≥4.0 mmol/L than in those with a serum Mg level <4.0 mmol/L. CONCLUSIONS: Modest effects on the clinical variables of infants with higher serum Mg levels were determined, whereas neither the duration of Mg treatment nor the cumulative Mg dose correlated with the clinical variables of the infants. Thus, in newborns with only moderately elevated serum Mg levels, serious adverse effects are unlikely.

Acetaminophen elevates unbound bilirubin levels by the glucose oxidase-peroxidase method.

BACKGROUND: Acetaminophen is widely administered to neonates but its effect on unbound bilirubin (UB) levels remains unclear. The aim of this study was to clarify whether administration of acetaminophen is related to an elevation of UB levels. METHOD: Infants with a birthweight of ˂1,500 g admitted to our neonatal intensive care unit between January 2017 and April 2020 were retrospectively reviewed. Seventy-one infants were enrolled, five of whom had received acetaminophen. Clinical data were analyzed when the highest UB value (UB peak) in each infant was recorded. Demographic data and information on treatment within the 24 h before the UB peak were also collected. UB was determined by the glucose oxidase-peroxidase (GOD-POD) method. Infants were categorized according to the presence or absence of acetaminophen administration (acetaminophen and no acetaminophen groups) within 24 h of the UB peak. The relationship between UB values and various clinical variables was then compared. RESULTS: Both the peak UB value and the ratio of gastrointestinal disease were higher in the acetaminophen group than in the no acetaminophen group. Univariate analysis revealed that a total of seven variables were potentially correlated with UB peak values (P < 0.10). Multivariate analysis showed that acetaminophen and direct bilirubin were independently associated with UB peak values. CONCLUSION: Our study suggests that administration of acetaminophen is related to higher UB levels by the GOD-POD method. UB values measured by the GOD-POD method should not be used in infants treated with acetaminophen for evaluation of bilirubin neurotoxicity avoidance.

Outcomes of Dysphagia Following Stroke: Factors Influencing Oral Intake at 6 Months After Onset.

PURPOSE: This study aimed to describe recovery of dysphagia after stroke. We determined the proportion of stroke survivors with dysphagia on admission, discharge, and 6 months after stroke. Additionally, the factors affecting oral feeding 6 months after stroke were explored. METHODS: A total of 427 acute stroke patients were recruited prospectively. Presence of dysphagia was evaluated on admission, weekly until recovery was achieved, and at discharge. We compared stroke survivors with dysphagia who had complete recovery, who had dysphagia but achieved oral feeding, and who required tube feeding. Patient-reported eating ability was evaluated at 6 months. Patients who achieved oral feeding by 6 months were compared to those who had persistent tube feeding need. RESULTS: Fifty-five percent of stroke survivors had dysphagia on initial evaluation (3.1 ± 1.4 days after admission) and 37% at discharge (21.1 ± 12.4 days). At 6 months, 5% of patients required tube feeding. Among those who had dysphagia at initial evaluation, 32% had resolution of dysphagia within two weeks, 44% had dysphagia but started oral feeding before discharge, and 23% required alternative means of alimentation (nasogastric tube feeding, percutaneous endoscopic gastrostomy, parental nutrition) throughout hospitalization. At 6 months, 90% of stroke survivors who achieved oral feeding by discharge continued with oral feeding. Patients who achieved oral feeding after discharge had less cognitive impairments on admission and a higher speech therapist intervention rate after discharge. CONCLUSIONS: More than half of stroke survivors had dysphagia but the vast majority were able to return to oral feeding by 6 months. Cognitive function and dysphagia rehabilitation interventions were associated with return to oral feeding after hospital discharge.

Corticotrophin-releasing hormone stimulation tests in late-onset circulatory collapse.

BACKGROUND: Late-onset circulatory collapse (LCC) is the transient development of refractory hypotension and oliguria after the early neonatal period, which may cause periventricular leukomalacia (PVL). The aim of this study was to evaluate the endogenous cortisol response to corticotrophin-releasing hormone (CRH) and determine whether it is effective for elucidating the pathology and selecting treatment in LCC. METHODS: This retrospective study examined infants admitted to the neonatal intensive care unit. Included were preterm (gestational age <34 weeks) infants who underwent CRH stimulation test and were treated for LCC with no obvious cause. Hydrocortisone (HC; 3.3-10 mg/kg) was given by bolus injection to the LCC infants. At 2 h after treatment, infants without a 20% rise in blood pressure (systolic or mean) from before treatment were defined as non-responsive to HC, and given catecholamine and/or vasopressin. RESULTS: Sixteen infants (median gestational age, 24 weeks 3 days; birthweight, 638 g) were eligible. Six of the infants had a good response to the CRH stimulation test. HC was effective in only three CRH good-response cases, and catecholamine and/or vasopressin was needed in the three other cases. HC was effective, however, for all CRH non-response cases. CONCLUSIONS: Although HC is the first-choice treatment for LCC, the CRH stimulation test facilitates prompt treatment of LCC, which may prevent PVL. The present findings help elucidate the pathology and aid in the selection of treatment for infants with LCC.

Calreticulin is highly expressed in pancreatic cancer stem-like cells.

Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). A P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2-D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P-CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P-CSLCs and did not correlate with the levels of CD44v9, another P-CSLC biomarker. Furthermore, the side population in the CRThigh /CD44v9low population was much higher than that in the CRTlow /CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P-CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.

Cysteine analogs with a free thiol group promote fertilization by reducing disulfide bonds in the zona pellucida of mice.

Archives of cryopreserved sperm harvested from genetically engineered mice, in mouse resource centers, are a readily accessible genetic resource for the scientific community. We previously reported that exposure of oocytes to reduced glutathione (GSH) greatly improves the fertilization rate of frozen-thawed mouse sperm. Application of GSH to in vitro fertilization techniques is widely accepted as a standard protocol to produce sufficient numbers of mice from cryopreserved sperm. However, the detailed mechanism of the enhancement of fertilization mediated by GSH in vitro is not fully understood. Here we focused on the chemical by determining the effects of its amino acid constituents and cysteine analogs on the fertilization of oocytes by frozen-thawed sperm. Furthermore, we determined the stability of these compounds in aqueous solution. We show here that l-cysteine (l-Cys), d-cysteine (d-Cys), or N-acetyl-l-cysteine (NAC) increased the rate of fertilization when added to the medium but did not adversely affect embryo development in vitro or in vivo. The levels of thiol groups of proteins in the zona pellucida (ZP) and the expansion of the ZP were increased by l-Cys, d-Cys, and NAC. These effects were abrogated by the methylation of the thiol group of l-Cys. NAC was the most stable of these compounds in the fertilization medium at 4°C. These results suggest that the thiol groups of cysteine analogs markedly enhance the fertilization rate of mouse oocytes.

Investigations of motility and fertilization potential in thawed cryopreserved mouse sperm from cold-stored epididymides.

Cold transport of epididymides from genetically modified mice is an efficient alternative to the shipment of live animals between research facilities. Mouse sperm from epididymides cold-stored for short periods can maintain viability. We previously reported that cold storage of mouse epididymides in Lifor® perfusion medium prolonged sperm motility and fertilization potential and that the sperm efficiently fertilized oocytes when reduced glutathione was added to the fertilization medium. Cryopreservation usually results in decreased sperm viability; an optimized protocol for cold storage of epididymides plus sperm cryopreservation has yet to be established. Here, we examined the motility and fertilization potential of cryopreserved, thawed (frozen-thawed) sperm from previously cold-stored mouse epididymides. We also examined the protective effect of sphingosine-1-phosphate (S1P) on sperm viability when S1P was added to the preservation medium during cold storage. We assessed viability of frozen-thawed sperm from mouse epididymides that had been cold-transported domestically or internationally and investigated whether embryos fertilized in vitro with these sperm developed normally when implanted in pseudo-pregnant mice. Our results indicate that frozen-thawed sperm from epididymides cold-stored for up to 48 h maintained high fertilization potential. Fertilization potential was reduced after cold storage for 72 h, but not if S1P was included in the cold storage medium. Live pups were born normally to recipients after in vitro fertilization using frozen-thawed sperm from cold-transported epididymides. In summary, we demonstrate an improved protocol for cold-storage of epididymides that can facilitate transport of genetically engineered-mice and preserve sperm viability after cryopreservation.

Rescue in vitro fertilization method for legacy stock of frozen mouse sperm.

Sperm cryopreservation has been widely adopted for maintenance of the genetically engineered mouse (GEM). The cryopreserved sperm are being exchanged among many institutes worldwide. However, the recipients are not always able to obtain high fertilization rates with the frozen sperm shipped from senders. In this study, we cryopreserved mouse sperm via various methods and performed in vitro fertilization (IVF) in which the combination of methyl-beta-cyclodextrin for sperm preincubation and reduced glutathione for insemination was used (the MBCD-GSH IVF). In addition, frozen sperm sent from the Jackson Laboratory (USA) were thawed and used for IVF in the same manner. The fertilization rates of both the sperm cryopreserved via the methods applied in some countries and the cryopreserved GEM sperm improved when used with the MBCD-GSH IVF method. Therefore, we strongly believe that the MBCD-GSH IVF method brings about relatively high fertilization rates with any strain of frozen mouse sperm.

Multiple ischemic strokes caused by nonbacterial thrombotic endocarditis because of gallbladder cancer: a case report.

We report a case of a 62-year-old woman with multiple ischemic strokes caused by nonbacterial thrombotic endocarditis (NBTE) because of gallbladder cancer. Transesophageal echocardiography showed NBTE on the mitral valve. The NBTE disappeared with anticoagulation treatment for 2 weeks. Abdominal computed tomography showed a gallbladder tumor that was surgically resected. Histopathologic studies showed poorly differentiated tumor cells and the production of mucin. Trousseau syndrome with gallbladder cancer is very rare. We suggest that the development of NBTE is related to the production of mucin.

Applications of cryopreserved unfertilized mouse oocytes for in vitro fertilization.

Since the first successful reports into oocyte freezing, many papers concerning the cryopreservation of mouse oocytes have been published. However, a simple and practical cryopreservation method for unfertilized C57BL/6 mouse oocytes, and an IVF system using these cryopreserved oocytes have yet to be established, in spite of the fact that C57BL/6 is the prevalent inbred strain and is used for large-scale knockout programs. In this study, unfertilized C57BL/6 mouse oocytes were cryopreserved via a simple vitrification method. After warming, IVF was performed using cryopreserved unfertilized oocytes and fresh sperm, cryopreserved unfertilized oocytes and cold-stored sperm, cryopreserved unfertilized oocytes and frozen sperm (C57BL/6 strain sperm), and cryopreserved unfertilized oocytes and frozen sperm derived from GEM strains (C57BL/6 background GEM strains). Nearly all of the cryopreserved oocytes were recovered, of which over 90% were morphologically normal. Those oocytes were then used for in vitro fertilization, resulting in 72-97% of oocytes developing into 2-cell embryos. A portion of the 2-cell embryos were transferred to recipients, resulting in live young being produced from 32-49% of the embryos. In summary, we established the simple and practical method of mouse oocyte vitrification with high survivability and developmental ability and the IVF using the vitrified-warmed oocytes with fresh, cold-stored or cryopreserved sperm with high fertility.

[A resected case of hilar cholangiocarcinoma treated with neoadjuvant chemoradiation therapy].

The patient was a 69-year-old woman with elevated levels of hepatobiliary enzymes. An abdominal computed tomography (CT) scan revealed an enhanced mass in the liver hilum with dilatation of the intrahepatic bile duct. We diagnosed hilar cholangiocarcinoma and administered neoadjuvant chemoradiation therapy because of the possibility of tumor cells remaining at the surgical margins. Radical surgery was performed and pathological examination showed the tumor to be Grade 2b according to the Oboshi-Shimosato classification. Although postoperative bile leakage and intra-abdominal abscess were observed, the patient was discharged on day 82 after surgery. The patient is still alive without recurrence at 17 months after the surgery. Neoadjuvant chemoradiation therapy has the potential to obtain a negative surgical margin in patients with hilar cholangiocarcinoma, which is likely to be positive for cancer cells at the surgical margin in preoperative diagnosis.

Establishment of a transport system for mouse epididymal sperm at refrigerated temperatures.

The exchange of genetically engineered mouse strains between research facilities requires transporting fresh mouse sperm under refrigerated temperatures. Although sperm generally maintains fertility for 48 h at cold temperatures, in vitro fertilization rates of C57BL/6 mouse sperm are low after 48-h cold storage. Furthermore, 48 h is often not sufficient for the specimens to reach their destinations. To increase the availability of this technology, we aimed to extend the cold storage period while maintaining sperm fertility. In this study, we determined the optimal medium for sperm preservation and evaluated the effect of reduced glutathione in the fertilization medium on sperm fertility after cold storage. We found that higher fertility levels were maintained after 72-h cold storage in the preservation medium Lifor compared with storage in paraffin oil, M2 medium, or CPS-1 medium. In addition, 1.0 mM glutathione enhanced sperm fertility. After transporting sperm from Asahikawa Medical University to our laboratory, embryos were efficiently produced from the cold-stored sperm. After transfer, these embryos developed normally into live pups. Finally, we tested the transport system using genetically engineered mouse strains and obtained similar high fertilization rates with all specimens. In summary, we demonstrated that cold storage of sperm in Lifor maintains fertility, and glutathione supplementation increased the in vitro fertilization rates of sperm after up to 96 h of cold storage. This improved protocol provides a simple alternative to transporting live animals or cryopreserved samples for the exchange of genetically engineered mouse strains among research facilities.

Cryopreserved allogenic fibroblast sheets: development of a promising treatment for refractory skin ulcers.

The purpose of this study was to investigate the therapeutic effect of cryopreserved allogenic fibroblast cell sheets in a mouse model of skin ulcers. It is necessary to reduce the cost of regenerative medicine for it to be widely used. We consider that cell sheets could be applied to various diseases if cryopreservation of allogenic cell sheets was possible. In this study, fibroblasts were frozen using a three-dimensional freezer. Freeze-thawed fibroblasts had ~80% cell viability, secreted ≥ 50% vascular endothelial growth factor, hepatocyte growth factor, and stromal derived factor-1α compared with non-frozen fibroblast sheets, and secreted approximately the same amount of transforming growth factor-ß1. There was no difference in wound-healing rates in the skin ulcer model between non-frozen and freeze-thawed fibroblast sheets regardless of autologous and allogenic cells. The degree of angiogenesis was comparable between autologous and allogenic cells. The number of CD3-positive cells in healed tissues was larger for allogenic fibroblast sheets compared with autologous fibroblast sheets. However, histopathological images showed that the fibrosis, microvascular density, and healing phase of the wound in allogenic freeze-thawed fibroblast sheets were more similar to autologous freeze-thawed fibroblast sheets than to allogenic non-frozen fibroblast sheets. These results suggest that allogenic freeze-thawed fibroblast sheets may be a promising therapeutic option for refractory skin ulcers.

Invasive thymoma extending to the right atrium with superior vena cava syndrome presenting massive intracardiac thrombosis immediately after the start of chemotherapy: an autopsy case report.

Invasive thymomas with intraluminal tumor thrombi are rare. Removal of the thymoma and infiltration of the superior vena cava (SVC) is a curative alternative. We report an autopsy case of invasive thymoma with intraluminal growth into the intracardiac right atrium extension. Furthermore, the patient died of massive intracardiac thrombosis 5 days after the start of chemotherapy. A 66-year-old man with SVC syndrome was referred to our hospital. He had been aware of swelling of the face for 6 months. The patient was diagnosed with invasive thymoma by a CT-guided needle biopsy of the anterior mediastinal mass. Contrast-enhanced chest computed tomography showed a mass in the anterior mediastinum extending to the SVC and right atrium. As a result of discussion with surgeons and radiotherapists, we planned a multidisciplinary treatment in which neoadjuvant chemotherapy would reduce the tumor size, and surgery and postoperative radiotherapy were followed by chemotherapy. He was administered neo-adjuvant chemotherapy with CBDCA + PTX (carboplatin, area under the curve = 6, and paclitaxel, 200 mg/m2). On the 4th day of chemotherapy, he suddenly developed obstructive shock due to intracardiac thrombosis in the right ventricle. We believe that chemotherapy may trigger rapid thrombus formation. If an invasive thymoma spreads into a large vessel or the right atrium, surgical treatment should be considered if possible. However, if surgery is impossible, administration of anticoagulants should be considered to prevent thrombus formation before chemotherapy.

Effect of 5-fluorouracil treatment on SN-38 absorption from intestine in rats.

5-Fluorouracil (5-FU)-based chemotherapies with irinotecan have been applied for the treatment of cancers, and a common dose-limiting toxicity is neutropenia and diarrhea. In this study, we investigated the effect of 5-FU treatment on expression levels of drug transporters for SN-38 transportation and SN-38 absorption from the intestine following 5-FU treatment. Expression levels of several drug transporters and nuclear receptors in rats after 5-FU treatment were evaluated. SN-38 absorption from the intestine was evaluated by SN-38 concentration levels in serum following SN-38 injection into the intestine of 5-FU treated rats. The levels of renal multidrug resistance protein 2 (Mrp2) on day 4 after treatment (400 mg/kg) showed significant upregulation, 359.2 ± 33.2% (mean ± S.E.) of control. Mrp2 levels in the intestine were downregulated to 26.2 ± 8.4% of control. 5-FU treatment (400 mg/kg) also significantly downregurated expression levels of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) to 41.2 ± 14.7%, 15.7 ± 4.3% of control, respectively. To evaluate SN-38 absorption from the intestine, SN-38 was loaded in to the intestine on day 4 after 5-FU treatment. Pretreatment with 5-FU significantly increased SN-38 concentration in the blood 30, 60 and 90 min after SN-38 administration. The area under the curve for SN-38 in the 5-FU group was significantly higher than in vehicle groups. 5-FU treatment decreased expression levels of P-glycoprotein and Bcrp in intestine. The present study suggests that combination chemotherapy of 5-FU with irinotecan (CPT-11) may elevate SN-38 absorption from intestine.

Perspectives of Multidisciplinary Professional Teams during Assessment Processes for ATD Selection in the Japanese Public Provision System.

Selection of assistive technology devices (ATDs), which are imperative for persons with disabilities to improve their quality of life, requires collaboration of users and multidisciplinary professionals. However, it is still unknown how to design and implement an adequate collaborative work flow and a professional team. Under Japanese governmental ATD provision system, based on the application by clients, ATDs are mainly selected through collaborative processes with the clients and health professionals in public organizations, rehabilitation counseling centers (RCCs). By employing qualitative study methods in this study, we investigated the ATD selection process in which health professionals in RCCs collaboratively assess clients with physical disabilities so as to support them in selecting the adequate ATDs. To identify the perspectives required for ATD selection completely, the assessment processes were recorded and analyzed with a pseudo setting in two RCCs. Content analysis of the conversations between the client and professionals revealed the characteristics of the information exchanged in the assessment processes. A total of 760 assessment items were identified, thus indicating a broad array of interest. Despite the richness of information collected for the assessment, half of the assessment items did not have corresponding items in the documents that were employed during the prescription process. Thematic analysis of the interviews that followed revealed the common values and collaborative processes in ATD selection, which were shared and elaborated among the staff in daily social interactions. To facilitate implementation of ATD provision in various areas with few resources, it may be effective to convert this tacit-to-tacit knowledge sharing into a more explicit sharing by promoting analyses of good practices.

Autologous transplantation of multilayered fibroblast sheets prevents postoperative pancreatic fistula by regulating fibrosis and angiogenesis.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is a serious complication after gastrointestinal or pancreatic surgery. Despite intensive investigations, the occurrence has not significantly decreased in the past decades. The aims of this study were to clarify the pathophysiology of POPF and establish the preventive measures using multilayered fibroblast sheets. METHODS: We developed a pancreatic fistula (PF) model of rat with transection of the splenic duct and surrounding pancreatic parenchyma. Multilayered fibroblast sheets prepared from tails were autologously transplanted to this model. The preventive effect was biochemically and histologically evaluated by measuring the ascitic levels of pancreatic enzymes and conducting immunohistochemistry and real-time polymerase chain reaction analyses of pancreatic tissue. Findings were compared to those obtained with acellular materials simply sealing the wound. RESULTS: In the PF model, the ascitic levels of pancreatic enzymes were transiently up-regulated. Inflammation and necrosis were histologically observed in a wide range. Islets were damaged even in remote areas. Transplantation of multilayered fibroblast sheets dramatically reduced the ascitic leakage of enzymes, suppressed inflammation, and broadly preserved the islets. Compared with acellular materials, these sheets offered superior prevention of cellular activity through the spaciotemporal regulation of fibrosis and angiogenesis. Notably, the leakage hole appeared to have been plugged with the fibrotic matrix, which might have been the most crucial mechanism minimizing pancreatic damage. CONCLUSIONS: The autologous transplantation of multilayered fibroblast sheets significantly prevented PF and protected the pancreas, underscoring the potential utility of this approach for POPF prevention.

Assessment of driving skills of a mobility scooter using driving operation logs.

A mobility scooter is a major assistive technology that replaces human ambulatory functions for people with disabilities. A license is often not required for driving a mobility scooter; therefore, less skilled drivers might create safety concerns. An effective way of reducing these safety risks is by assessing the driving skills of users. The existing assessment measures mostly score the task performance using manual observations. In this study, we have developed a novel assessment system that logs the driving operations by using add-on sensors. This system can monitor the operations of a mobility scooter including the angles of the throttle lever and the steering tiller. The subjects were seven older adults who participated in the driving test involving six tasks; the driver performances were video recorded, and the vehicle operation data were logged. The video analysis showed that two subjects crashed their scooters into objects or made contact with objects during the test course. To extract the characteristic patterns of the operations from the logs, 2D histograms of the operational status durations were investigated for each subject and task. Subsequent analysis of the operation logs identified the two subjects who had crashed their vehicles during the test drive. Our results proved that the driving operation logs could be used complementarily as a simple and low-cost tool for assessing a person's driving skills.

Aneuploidy predicts outcome in patients with endometrial carcinoma and is related to lack of CDH13 hypermethylation.

PURPOSE: Many investigators have reported that aneuploidy detected by flow cytometry is a useful prognostic marker in patients with endometrial cancer. Laser scanning cytometry (LSC) is a technology similar to flow cytometry but is more feasible for clinical laboratory use. We evaluated the usefulness of DNA ploidy detected by LSC as a prognostic marker in patients with endometrial cancer and investigated genetic and epigenetic factors related to aneuploidy. EXPERIMENTAL DESIGN: Endometrial cancer specimens from 106 patients were evaluated. The methylation status of CDH13, Rassf1, SFRP1, SFRP2, SFRP4, SFRP5, p16, hMLH1, MGMT, APC, ATM, and WIF1 and mutations in the p53 and CDC4 genes were investigated. LSC was carried out to determine DNA ploidy. Fluorescence in situ hybridization was done with chromosome-specific centromeric probes to assess chromosomal instability. RESULTS: Univariate and multivariate analyses revealed that p53 mutation and lack of CDH13 hypermethylation associated positively with aneuploidy. Univariate analysis showed that aneuploidy, chromosomal instability, and lack of CDH13 hypermethylation as well as surgical stage were significantly predictive of death from endometrial cancer. Furthermore, multivariate analysis revealed that stage in combination with either DNA aneuploidy or lack of CDH13 hypermethylation was an independent prognostic factor. CONCLUSION: These results suggest that analysis of DNA ploidy and methylation status of CDH13 may help predict clinical outcome in patients with endometrial cancer. Prospective randomized trials are needed to confirm the validity of an individualized approach, including determination of tumor ploidy and methylation status of CDH13, to management of endometrial cancer patients.