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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

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-β1. 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.

BACKGROUND Antenatal magnesium sulfate (MgSO4 ) has been used in mother, 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 the serum Mg concentration, cumulative Mg dose, and duration of maternal antenatal Mg treatment. 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.

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.

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.

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.Clinical Relevance—The driving operation logging system that we developed can accurately and objectively evaluate the driving skills of mobility scooter drivers, such as steering and speed adjustment. Further, by accumulating such objective data, the system can be used for predicting and preventing accidents. Thus, the system will provide secure and safe community mobility for older persons and thereby improve their quality of life.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. The pathological mechanism of FPIES is intestinal inflammation, and cell-mediated hypersensitivity is presumed to play an important role in its development. Case Report: The first case in which significant fetal intestinal distension suggested fetal onset of FPIES is reported. A 2,334-g male was born at 34 weeks by vaginal delivery. Results: In utero, he had significant intestinal distension on ultrasonography and MRI. A few hours after the first feeding, he produced bloody stool and showed abdominal distension. In this case, FPIES was not only caused by cow’s milk protein diagnosed clinically and by an allergen-specific lymphocyte stimulation test, but also by breast milk diagnosed by oral food challenge. The clinical course and laboratory results strongly suggested not only fetal sensitization but also fetal onset. Conclusion: This report might be helpful for prompt diagnosis and treatment and, furthermore, lead to elucidation of the pathogenesis and pathophysiology of FPIES.

We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test

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

We evaluated the viability of free fat grafts in the thoracic cavity using 3-month old male swine (n = 2). After left caudal lobectomy, 1-3 g of subcutaneous fat tissue harvested via the thoracotomy site was implanted in the chest cavity. At re-thoracotomy 6 weeks after implantation, all of the implanted fat grafts (n = 15) were found to have closely adhered to the parietal pleura and visceral pleura. There was a significant decrease by ∼30% in the weight of the fat grafts after implantation. Regardless of the weight loss, the implanted fat graft showed normal structuring without scar formation in the central area. Our results may suggest that free fat pads, which weighed up to 3 g, were successfully cultured in the thoracic cavity until the implanted tissues integrated into the surrounding tissues. Therefore, the free fat pad can be used as a biomaterial for some purposes in thoracic surgery.

Sago palm is a highly efficient starch-producing plant found in humid tropical zones. In the areas where sago palms are cultivated, its plantation methods and food cultures have been conveyed from generation to generation. Recently, it is increasingly seen as an important agricultural product and crop whose cultivation can lead to more fulfilling lives for local people. However, there are very few food uses for sago starch as a main ingredient in Japan. In order to increase sago starch usage across Japan, it is exceedingly important to introduce high-quality sago starch. Also it is crucial to publicize its attractiveness, positive characteristics, and its specific and potential usages. Accordingly, in this report, the physicochemical characteristics and optimal cooking properties of sago starch were examined through investigating sago starch usage in the cooking processes of udon, Chinese noodles, Chinese vermicelli, kuzukiri (fen pi), gomadofu, kamaboko, warabimochi, kuzuzakura nama-yatsuhashi, mushiyokan, pie filling, blancmange, and biscuits.

The objective of this study is to develop a special self-training program for students of occupational therapy forthe National Examination and to explore changes in their scholastic ability and in their consciousness as well as the relationbetween their scholastic ability and their consciousness. The new study method was developed by referring to the KJ Method.The subjects were 28 students in their junior and senior years who were enrolled in the Department of Occupational Therapyof Teikyo University of Science. The examination of the scholastic ability of the students and a questionnaire to makeevaluation of consciousness was administrated to the juniors at the start and completion of the program, and to the seniors atthe completion of the program. As a result, it was found that improvement of scholastic ability was not significant. This mayhave been due to the inability of students with poor abilities to maintain their motivations since only a single, advanced methodof study was indicated to them. Next, it was found that there is a relationship between the consciousness and the scholasticability of the students. Further, the ability to obtain a high score was related to possession of basic information about theNational Examination. In addition, whereas the consciousness of students with good ability to obtain high scores was foundto converge to a single trend, that of students with poor ability to do so was found to be widely dispersed. These findingssuggest that it is necessary to make modifications to the program in accordance with the scholastic ability of the students.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have been recognized as metabolic disorders characterized by fatty accumulation in the liver without alcohol consumption. The diseases can cause metabolic syndromes, consisting of obesity, diabetes mellitus (DM), dyslipidemia and hypertension. For the treatment of NAFLD/NASH, losing weight by exercise or diet remains the standard treatment, because no effective pharmacological therapy has yet been developed for NAFLD/NASH. Two incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), stimulate glucose-mediated insulin production in pancreatic β cells. Incretin has also been reported to have various extra-pancreatic effects, including the regulation of hepatic glucose production, appetite and satiety, as well as the stimulation of afferent sensory nerves. Therefore, incretin may have potential as a novel therapeutic agent for NAFLD/NASH.

Background The aim of this study was to examine the effects on functional and psychosocial parameters and long-term care utilization of a preventive home visit program for ambulatory frail Japanese elders. Methods Eligible participants (n = 323) were randomly assigned to intervention (n = 161) or control group (n = 162). Nurses and care managers provided structured preventive home visits to the intervention group participants every 6 months over 2 years. Activities of daily living (ADLs), instrumental activities of daily living (IADLs), depression, and social support were collected via mail questionnaire at baseline and at 12- and 24-month follow-up points. The utilization of long-term care insurance was documented over the period. Results Two-way analysis of covariance did not show significant outcome differences overall. In a pre-planned subgroup analysis for participants who had at least one ADL dependency at baseline, those in the intervention group (N = 105) were significantly less likely to deteriorate over 2 years in their function and depression than those in the control group (N = 100): ADLs (p = .0311), IADLs (p = .0114), depression (p = .0001). The total long-term care costs over 2 years in the intervention group (36,001 credits) were higher than in the control group (26,022 credits) (nonsignificant), and elders in the intervention group utilized significantly more community and institutional long-term care services than those in the control group over the period 7 months to 15 months after the intervention started. Conclusions The results suggest that a preventive home visit program might be ineffective on functional and psychosocial status among ambulatory frail elders overall, although it might significantly improve ADLs, IADLs and depression for those with ADL dependency.

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.

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.

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.

The field of molecular biology currently faces the need for a comprehensive method of evaluating individual differences derived from genetic variation in the form of single nucleotide polymorphisms (SNPs). SNPs in human genes are generally considered to be very useful in determining inherited genetic disorders, susceptibility to certain diseases, and cancer predisposition. Quick and accurate discrimination of SNPs is the key characteristic of technology used in DNA diagnostics. For this study, we first developed a DNA microarray and then evaluated its efficacy by determining the detection ability and validity of this method. Using DNA obtained from 380 pregnant Japanese women, we examined 13 polymorphisms of 9 genes, which are associated with the metabolism of environmental chemical compounds found in high frequency among Japanese populations. The ability to detect CYP1A1 I462V, CYP1B1 L432V, GSTP1 I105V and AhR R554K gene polymorphisms was above 98%, and agreement rates when compared with real time PCR analysis methods (kappa values)showed high validity: 0. 98 (0.96), 0.97 (0.93), 0.90 (0.81), 0.90 (0.91), respectively. While this DNA microarray analysis should prove important as a method for initial screening,it is still necessary that we find better methods for improving the detection of other gene polymorphisms not part of this study., 近年，一遺伝子多型（SNPs）に由来する個々の感受性を包括的に評価する方法が必要とされている．ヒト遺伝子におけるSNP は，遺伝的な疾患，特定の疾病に対する感受性，癌などの素因のひとつとして考えられている．そのため，迅速で正確なSNPs判定法が求められている．本研究では，環境化学物質代謝に関与する遺伝子多型を判定するためのDNA マイクロアレイを開発し，その効力と信頼性を380人の日本人妊婦の血液を用いて，日本人で変異型.度の高い９遺伝子13多型について検討した．CYP1A1 I462V，CYP1B1 L432V，GSTP1 I105V，AhR R554K 遺伝子多型に対する検出力は98％以上の値を示すとともに，リアルタイムPCR 法による結果との比較による信頼度（κ係数）は，高い値を示した（それぞれ，0.98（0.96），0.97（0.93），0.90（0.81），0.90（0.91））．本研究のマイクロアレイ法は，検出できなかった遺伝子多型について改善する必要がある一方で，初期のスクリーニング方法として重要である．

Purpose This study aimed to evaluate predictive factors involved in efficacy and safety in Japanese infants who received theophylline therapy to prevent apnea of prematurity (AOP) after weaning from mechanical ventilation. Methods We retrospectively reviewed the medical records of infants who were administered intravenous aminophylline (theophylline ethylenediamine) for AOP at the neonatal intensive care unit, Kagoshima University Hospital, Japan, between January 2009 and June 2013. Results A total of 100 infants were evaluated as two separate groups in terms of efficacy and safety of theophylline. Sixty-seven (67.0%) infants had effective theophylline therapy. Multivariate logistic regression analysis showed that gestational age at birth was significant, with an odds ratio of 0.59 (p < 0.001). Receiver operating characteristic analysis showed that the cut-off value was 31.1 weeks old for predicting the efficacy of theophylline (specificity, 66.7%; sensitivity, 86.6%; p < 0.001; area under the curve, 0.750; 95% confidence interval, 0.45–0.74). Adverse reactions were identified in 21 (21.0%) infants. Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01). Conclusions Physicians need to be aware of the possibility that theophylline fails to produce therapeutic effects for extubation in infants aged less than 31.1 weeks old, and adverse reactions can easily develop when theophylline is administered soon after birth.

Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having the aryl hydrocarbon receptor (AhR) wild type genotype (Arg/Arg; 211 g ± 76 g; 1.2 cm ± 0.4 cm, p < 0.01 and p < 0.01, respectively), the CYP1A1 variant genotype (m1/m2 + m2/m2; 170 g ± 64 g, 0.8 cm ± 0.3 cm, p < 0.01 and p < 0.05, respectively), or the GSTM1 null genotype (171 g ± 58 g, 0.6 cm ± 0.3 cm, p < 0.01 and p < 0.05, respectively). When combinations of these genotypes were considered, birth weight and length were significantly lower for infants of continuously smoking women in the AhR wild type + CYP1A1 variant group (315 g ± 116 g; 1.7 cm ± 0.6 cm, p < 0.01 and p < 0.01, respectively) and in the CYP1A1 variant + GSTM1 null group (237 g ± 92 g; 1.3 cm ± 0.5 cm, p < 0.05 and p < 0.01, respectively). These genotypes did not confer adverse effects among women who had never smoked; therefore, maternal smoking in combination with maternal AhR, CYP1A1 and GSTM1 genetic polymorphisms may adversely affect infant birth size.

There have been several epidemiological and experimental studies about styrene from the neuroendocrinological viewpoint. Some reported that styrene exposure affected the neuroendocrinological system and enhanced prolactin (PRL) secretion, but others have denied those effects. It was assumed that styrene exposure caused depletion of dopamine (DA), which is a PRL inhibitor, and that, in consequence, the PRL level increased. However, not only DA but also many other factors control PRL secretion. Therefore, the mechanism of hypersecretion of PRL has not yet been clearly elucidated. In addition, effects of styrene on the female reproductive system have been reported, but the susceptibility needs to be further studied. Therefore, to investigate what causes hypersecretion of PRL and how different the susceptibility is in males and females, we studied acute effects of styrene exposure on the neuroendocrinological system in male and female rats. Immediately after exposure to 150 ppm styrene vapor for 10 days (8 h/day), male and female rats were killed, and blood and brain samples were collected. The styrene concentration in blood, hormones such as PRL, growth hormone (GH) and thyroid-stimulating hormone (TSH) in plasma and neurotransmitters in various brain regions were measured. The styrene concentration in the blood of female rats was higher than that in male rats, and the PRL level was significantly increased in female exposed rats compared with controls. No significant change was observed in male rats. We did not observe any significant changes in DA, 5-hydroxytryptamine (5-HT) or their metabolites. Because neurotransmitters were not affected in either male or female rats, the mechanism enhancing PRL secretion remains unclear. These results suggest that styrene exposure may cause hypersecretion of PRL and that the sensitivity to styrene exposure of the female may be higher than that of the male.

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Biochemistry following peer review. The definitive publisher-authenticated version Saijo, Y. ; Sata, F. ; Yamada, H. ; Suzuki, K. ; Sasaki, S. ; Kondo, T. ; Gong, Y. ; Kato, EH. ; Shimada, S. ; Morikawa, M. ; Minakami, H. ; Kishi, R., MHR: Basic science of reprod. Medicine, 10(10), 2004, 729-733 is available online at: http://molehr.oxfordjournals.org/cgi/content/abstract/10/10/729., The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40–1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68–2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.

Culture not only assigns a name to occupation through its language, but it also shapes the form it takes and the meaning with which it is imbued. When an individual chooses an occupation, psychological and physical concerns as well as cultural practices, values, and beliefs come into play. Although occupational therapists are trained to be culturally competent, their grasp of the importance of cultural considerations can be enhanced through detailed accounts of the way in which such concerns affect clinical practice. In this paper, I describe in detail my observations of how differences between American and Japanese culture have created tensions in occupational therapy practice in Japan. Further, largely through a case presentation, I illustrate the necessity for incorporating in-depth cultural considerations as a central part of the occupational therapy process. I argue that the study of culture and the production of culture-specific occupational therapy theories will contribute to best practice. I conclude by demonstrating that universal as well as culture-specific theories are needed to nurture occupational therapy.

Objective To investigate the relationships between recurrent pregnancy loss and single nucleotide polymorphisms (−634C→G and −174G→C genotypes) in the promoter region of the interleukin (IL)-6 gene in the Japanese population. Design A case–control study. Setting Obstetrics and gynecology department of a university hospital. Patient(s) Cases were 76 women with recurrent pregnancy loss; controls were 93 fertile women. Intervention(s) Determination of IL-6 promoter gene polymorphisms performed by polymerase chain reaction and gel electrophoresis. Main outcome measure(s) Frequency and distribution of the promoter region of the IL-6 gene allele. Results There was a significant difference in the −634C→G genotype frequency (CC vs. CG/GG) between women with recurrent pregnancy loss and controls. The risk of recurrent pregnancy loss was lower in the carriers of the G allele than in women with the wild type (CC) (odds ratio=0.46; 95% confidence interval=0.24-0.91). On the other hand, we did not detect any carrier of −174C among the 169 subjects. Conclusion(s) The results suggest that, in the Japanese population, women carrying the −634G allele of the IL-6 gene might have a decreased risk of recurrent pregnancy loss.

The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P

The purpose of the present study was to establish an effective immunotherapy by skewing the cosignal balance to be on the positive side by using the combination of monoclonal antibody (mAb) against 4-1BB also known as Cluster of Differentiation (CD) 137 as a co-stimulatory effector and to programmed death-1 (PD-1) to blockade the immune checkpoint.Mice implanted with 1×10(5) CT26 cells were treated with anti 4-1BB mAb alone, anti PD-1 mAb alone, or both anti 4-1BB mAb and anti PD-1 mAb. Immune cell populations were analyzed by flow cytometry. Tumor-infiltrating T-cells were evaluated by immunohistochemistry.Mice treated with the combination therapy had the best antitumor response that resulted in complete tumor rejection. The numbers of CD4(+) interferon (IFN)-γ(+) and CD8(+) IFN-γ(+) T-cells were significantly higher in the combination group. The number of tumor-infiltrating T-cells was significantly increased in the combination therapy.The therapeutic strategy of targeting co-signal molecules has promising clinical applications in the future.

By introducing the technology of the virtual desktop infrastructure (VDI) to e-learning systems, the identical learning environment can be provided to the learner at any time, and at any place, and also even if the learner stops learning or working, he can restart it by different terminals including different operating systems. On the other hand, the quality of screen images on the desktop would be affected by the quality of service (QoS) of the network, since the screen images are transferred to the client from the server by their transfer protocol. In this paper, we discuss the influence of the QoS upon the learning styles caused by the usability over the VDI. By constructing the experimental network using network emulators, we evaluate and discuss the influence of the QoS such as a round trip delay time (DT) and a bandwidth (BW) upon learning style measured by the quality of experience (QoE). As a result, we clarify the relationships between the QoS of the network and the QoE of the e-learning styles. Keywords— e-learning; learning style; quality of service; quality of experience; virtual desktop infrastructure; DaaS

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.

Cyclin B mRNA stored in immature zebrafish oocytes is translationally activated upon the stimulation of 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-DP), an event prerequisite for initiating oocyte maturation in this species. We investigated localization of cyclin B mRNA in zebrafish oocytes. Cyclin B mRNA was found to be exclusively localized as an aggregation along the cytoplasm at the animal pole of full-grown immature oocytes. When oocytes were treated with 17alpha,20beta-DP, a meshwork of microfilaments in the oocyte cortex disappeared and the aggregation of cyclin B mRNA dispersed just prior to the initiation of cyclin B synthesis and germinal vesicle breakdown (GVBD). Cytochalasin B, but not nocodazole or taxol, deformed the aggregation of cyclin B mRNA, indicating the involvement of microfilaments in organizing this form. Like 17alpha,20beta-DP, cytochalasin B (10 microg/ml) induced both complete dispersion of the aggregation and translational activation of cyclin B mRNA, forcing the oocytes to undergo GVBD without 17alpha,20beta-DP. Conversely, disturbance of the aggregation of cyclin B mRNA with a low concentration (1 microg/ml) of cytochalasin B inhibited 17alpha,20beta-DP-induced GVBD. These results suggest that the direct change in cyclin B mRNA from the aggregated form to the dispersed form is responsible for translational activation of the mRNA during zebrafish oocyte maturation.

Purpose. To evaluate an interaction between simvastatin and itraconazole in in vitro studies and to attempt a quantitative prediction of in vivo interaction in humans.

The structure of a new anthocyanin from Salvia uliginosa petals has been identified as delphinidin 3-O-[6-O-(p-coumaroyl)-β-d-glucopyranoside]-5-O-[4-O-acetyl-6-O-malonyl-β-d-glucopyranoside] using mass spectroscopy and NMR. This compound constitutes the anthocyanin component of the pigment responsible for blue flower colour in S. uliginosa.

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.

Objective. This study examined the effectiveness of microwave ovens in assisting elderly persons with disabilities with cooking food. Method. The participants were five elderly persons who had gross motor, fine motor, or vision impairments but no cognitive impairments. Before the study, none of the participants owned or operated a microwave oven. In this single-subject design off our phases (ABAB), training in microwave oven use was provided between the first A (baseline) and first B (intervention) phases. Participants had access to the microwave oven in their homes only during the B phases. Each phase lasted for 3 weeks, for a total of 12 weeks. The frequency of using cooking appliances, the number of food items prepared, and the time spent preparing meals were recorded through daily self-reports. Results. All participants showed an increase in the frequency of using cooking appliances for at least one of the two B phases, although they showed different patterns. The number of food items prepared increased in the B phases, except for two participants who were ill. With the introduction of the microwave oven, time spent preparing meals decreased for all five participants, and their participation in meal preparation increased. Although not measured as a study variable, results suggest that the quality of diet also improved with microwave oven use. Conclusion. Occupational therapy practitioners who serve elderly clients might consider recommending microwave ovens for those who do not have cognitive impairments but who are having difficulty with cooking because of vision impairments or physical disabilities.

Binuclear cells have been occasionally observed in nonneoplastic and carcinoma cells. However, in clinical cases, few reports have analyzed and discussed the origins and features, including the proliferative capacity, of binuclear cells. We describe the case of a 75-year-old man with gastric cancer with microscopically prominent binuclear cells in the resected tissue and ascitic fluid. Image cytometry and chromosomal analysis were performed on cells isolated from the ascitic fluid. The DNA histogram pattern showed aneuploidy and the fluorescence in situ hybridization pattern of centromeres 7 and 11 was similar to that of most other mononuclear cancer cells. Furthermore, the binuclear cells showed low proliferative capability based on 5-bromo-2'-deoxyuridine incorporation. Our results demonstrated that the binuclear cells were derived from mononuclear aneuploid cells through incomplete cell division, and, in this case, may have impaired proliferative capacity.

We report a case of Isaacs' syndrome associated with Hashimoto disease. A 26-year-old woman, who had a past history of Hashimoto disease, complained of involuntary movements and muscle cramp in lower extremities. On examination, myokymia was seen in lower extremities. Myokymia was observed even during sleep, and worsened by exercise or bathing. The antibody against voltage-gated potassium channel (VGKC) was positive. Myokymic discharges were recorded with needle EMG in lower extremities. The patient was diagnosed as having Isaacs' syndrome. Isaacs' syndrome tends to be associated with some other autoimmune diseases. We discussed the correlation between Isaacs' syndrome and autoimmune disease. About 23% of Isaacs' syndrome cases are associated with some other autoimmune diseases and myasthenia gravis was most common. This is the first case report of Isaacs' syndrome associated with Hashimoto disease in Japan.

Combinations of imidacloprid and permethrin were frequently used to control harmful arthropod of companion animals. The inhibitory effects on blood-feeding activity of mosquitoes in dogs raised under outdoor conditions were evaluated by using combination of 10% (w/v) of imidacloprid and 50% (w/v) of permethrin as spot-on form. Dogs in the treated group received the combination imidacloprid/permethrin spot-on. After treatment, dogs in the control and treated groups were kept separately from the evening (17:00) to the morning of the following day (09:00) in two different kennels installed outdoors to mimic realistic dog-raising conditions. Mosquitoes in the kennels were collected by light traps placed in the kennels and a sweep net to determine evidence of blood feeding, and for species identification. Mosquitoes were collected at Days 5, 3 and 1 before agent treatment, and the Day of treatment, and Days 3, 7, 14, 21, 28, 35 and 42 after treatment. The percentages of blood-fed mosquitoes measured at Days 0, 3, 21, 28 and 42 after treatment were statistically significantly lower (p < 0.01) in the treated group than in the control group. The most commonly collected mosquito, Culex tritaeniorhynchus, revealed statistically significant lower percentages (p < 0.01) of blood-fed mosquitoes in the treated group than in the control group at the Day of treatment, and Days 3, 7, 21, 28 and 42 after treatment. It appeared that the test agent was effective in inhibiting blood feeding by adult female mosquitoes, and the efficacy lasts for 42 days after treatment under outdoor conditions.

Although elevated cell proliferation activity is one of the most remarkable features known to characterize malignant ovarian germ cell tumors (MOGCTs), abnormalities in cell cycle regulation have yet to be thoroughly investigated in MOGCTs. Forty-two MOGCTs were immunohistochemically examined to determine their cyclin E and p27 Kip1 (p27) expression in correlation with their cell proliferation activity and clinicopathological features. Cytosine methylation of p27 gene promoter CpG islands was estimated by methylation-specific PCR. The labeling index (LI) was calculated as a percentage of the positively stained tumor cells per total tumor cells counted. p27 LIs showed a significant inverse correlation with Ki-67 LIs in MOGCTs examined (p

We evaluated the effects of inhaled di(2-ethylhexyl)phthalate (DEHP) on the onset of puberty and on postpubertal reproductive functions in prepubertal female rats. DEHP was administered by inhalation at doses of 0, 5, and 25 mg/m3 to groups of female rats for 6 h/day, 5 contiguous days/week from postnatal days (PNDs) 22 to 41 and to PND 84. The onset of puberty was determined by daily examination for vaginal opening (VO) and first estrous cycle. Reproductive function was evaluated by observing estrous cyclicity from PNDs 49 to 84. Upon completion of exposure, the rats were sacrificed at PND 42 and PNDs 85-88 during the diestrous stage. DEHP exposure advanced the age of VO and first estrous cycle, and serum cholesterol, luteinizing hormone, and estradiol levels were significantly elevated in the 25-mg/m3 DEHP group. Irregular estrous cycles were observed more frequently in DEHP-exposed rats, and serum cholesterol decreased in DEHP-exposed rats in adulthood; RT-PCR showed that the expression of aromatase mRNA, encoding a rate-limiting enzyme that catalyzes the conversion of testosterone to estradiol, was elevated in the 25-mg/m3 DEHP group. These data suggest that inhaled DEHP may advance the onset of puberty and alter postpubertal reproductive functions.

The CYP17 gene encodes the enzyme cytochrome P450c17alpha, which mediates both 17alpha-hydroxylase and 17,20-lyase activity in the steroid biosynthesis pathway. A T--C polymorphism in the 5' promoter region of CYP17 has been described. To examine the association between recurrent pregnancy loss (RPL) and a polymorphism in CYP17, a case-control study of 117 cases with RPL and 164 controls was conducted. This polymorphism was investigated by PCR/restriction fragment length polymorphism using DNA from peripheral lymphocytes. The T--C transition in the variant allele (A2) creates a new recognition site for the restriction enzyme MspA1, which permits designation of the wildtype allele (A1) and A2. Women with the A2 allele of CYP17 had an increased risk of RPL [A1/A1 genotype (reference); A1/A2 genotype: odds ratio (OR), 1.68; 95% confidence interval (CI), 0.94-3.01; A2/A2 genotype: OR, 2.37; 95% CI, 1.16-4.83; P trend, 0.016]. Additionally, there was a similar tendency for the increased risk of primary RPL [A1/A1 genotype (reference); A1/A2 genotype: OR, 2.14; 95% CI, 1.14-4.01; A2/A2 genotype: OR, 2.50; 95% CI, 1.16-5.41; P trend, 0.015]. These results suggest that possession of the A2 variant of CYP17 may predispose to an increased risk of RPL with a gene dosage effect.