Search

On 24 March 2020, an announcement was made that the Tokyo 2020 Olympic and Paralympic games would be postponed until 2021 due to the coronavirus pandemic. Athletes and their coaches have experience...

Because treatment for postsurgical pain (PSP) remains a major unmet medical need, the emergence of safe and innovative nonopioid drugs has been strongly coveted. Tetrahydrobiopterin (BH4) is an interesting molecule for gaining a better understanding the pathological mechanism of neuropathic pain. However, whether BH4 and its pathway are involved in the pathogenesis of PSP remains unclear. In this study, we found that early in a rat paw incision model, the gene expression of GTP cyclohydrolase 1 (GTPCH) and sepiapterin reductase (SPR), BH4-producing enzymes in the de novo pathway, were significantly increased in incised compared with naive paw skin. Although a significant increase in GTPCH protein levels was observed in incised paw skin until only 1 day after incision, a significant increase in BH4 levels was observed until 7 days after incision. In vivo, Spr-knockout mice showed an antinociceptive phenotype in the hind paw incision compared with the wild-type and Spr heterozygote groups. Furthermore, QM385, the SPR inhibitor, showed a significant dose-dependent, antinociceptive effect, which was supported by a reduction in BH4 levels in incised skin tissues, with no apparent adverse effects. Immunohistochemical analysis demonstrated that macrophages expressing GTPCH protein were increased around the injury site in the rat paw incision model. These results indicate that BH4 is involved in the pathogenesis of PSP, and that inhibition of the BH4 pathway could provide a new strategy for the treatment of acute PSP.

Acid sphingomyelinase (ASM) is a lysosomal hydrolase that degrades sphingomyelin into ceramide and phosphocholine. Recent crystallographic studies revealed the functional role of the N-terminal ASM saposin domain. ASM deficiency due to mutations in the ASM-encoding sphingomyelin phosphodiesterase 1 (SMPD1) gene causes an autosomal recessive sphingolipid-storage disorder, known as Niemann-Pick disease Type A (NPA) or Type B (NPB). NPA is an early-onset neuronopathic disorder, while NPB is a late-onset non-neuronopathic disorder. A homozygous one-base substitution (c.398G>A) of the SMPD1 gene was identified in an infant with NPA, diagnosed with complete loss of ASM activity in the patient's fibroblasts. This mutation is predicted to substitute tyrosine for cysteine at amino acid residue 133, abbreviated as p.C133Y. The patient showed developmental delay, hepatosplenomegaly and rapid neurological deterioration leading to death at the age of 3 years. To characterize p.C133Y, which may disrupt one of the three disulfide bonds of the N-terminal ASM saposin domain, we performed immunoblotting analysis to explore the expression of a mutant ASM protein in the patient's fibroblasts, showing that the protein was detected as a 70-kDa protein, similar to the wild-type ASM protein. Furthermore, transient expression of p.C133Y ASM protein in COS-7 cells indicated complete loss of ASM enzyme activity, despite that the p.C133Y ASM protein was properly localized to the lysosomes. These results suggest that the proper three-dimensional structure of saposin domain may be essential for ASM catalytic activity. Thus, p.C133Y is associated with complete loss of ASM activity even with stable protein expression and proper subcellular localization.

This study aimed to evaluate the capability of a piezoelectric sensor to detect a heart murmur in patients with congenital heart defects. Heart sounds and murmurs were recorded using a piezoelectric sensor and an electronic stethoscope in healthy neonates (n = 9) and in neonates with systolic murmurs caused by congenital heart defects (n = 9) who were born at a hospital. Signal data were digitally filtered by high-pass filtering, and the envelope of the processed signals was calculated. The amplitudes of systolic murmurs were evaluated using the signal-to-noise ratio and compared between healthy neonates and those with congenital heart defects. In addition, the correlation between the amplitudes of systolic murmurs recorded by the piezoelectric sensor and electronic stethoscope was determined. The amplitudes of systolic murmurs detected by the piezoelectric sensor were significantly higher in neonates with congenital heart defects than in healthy neonates (p < 0.01). Systolic murmurs recorded by the piezoelectric sensor had a strong correlation with those recorded by the electronic stethoscope (ρ = 0.899 and p < 0.01, respectively). The piezoelectric sensor can detect heart murmurs objectively. Mechanical improvement and automatic analysis algorithms are expected to improve recording in the future.

We describe a medicinal chemistry approach to the discovery of a novel EP1 antagonist exhibiting high potency and good pharmacokinetics. Our starting point is 1, an EP1 receptor antagonist that exhibits pharmacological efficacy in cystometry models following intravenous administration. Despite its good potency in vitro, the high lipophilicity of 1 is a concern in long-term in vivo studies. Further medicinal chemistry efforts identified 4 as an improved lead compound with good in vitro ADME profile applicable to long term in vivo studies. A rat fracture study was conducted with 4 for 4 weeks to validate its utility in bone fracture healing. The results suggest that this EP1 receptor antagonist stimulates callus formation and thus 4 has potential for enhancing fracture healing.

IntroductionA major concern is that few cancer survivors meet the guidelines for recommended levels of physical activity. No studies have investigated physical activity among breast cancer survivors nationwide in Japan. Therefore, the aims of this study are to identify the levels of physical activity among breast cancer survivors, to examine factors-related physical activity among breast cancer survivors and to identify breast cancer survivors’ preferences for and interest in exercise programmes in order to inform the future programme development.Methods and analysisWe will administer a cross-sectional survey using a self-report questionnaire to breast cancer survivors. At each of 50 facilities selected to include a variety of institutional backgrounds according to the population distribution of different regions throughout Japan, we will consecutively distribute the questionnaire to 30 outpatients who have completed initial treatments, except for hormone therapy. The target sample size is 1500 survivors. We will calculate descriptive statistics for each measurement item and perform univariate and multivariate analyses using outcome measures (eg, physical activity and quality of life) related to physical, psychological, social and environmental factors.DiscussionThis is the first nationwide survey of physical activity levels among breast cancer survivors in Japan. Identifying the factors associated with physical activity will help us to develop, disseminate and implement programmes that encourage more survivors to adhere to physical activity guidelines.Ethics and disseminationThe protocol was approved by the Institutional Review Board (IRB) of the National Cancer Center on 11 January 2019 (ID: 2018–295). In addition, many of the participating facilities required ethical approval from their local IRBs, while others did not. Accordingly, approval from the local IRBs of individual facilities was obtained when required. The findings will be disseminated through peer-reviewed publications and conference presentations.

AIM Bubbly/cystic appearance on chest X-ray (CXR) is an important factor in cases of severe bronchopulmonary dysplasia (BPD). We aimed to determine whether CXR -based BPD classifications obtained in extremely preterm infants with oxygen dependency at 28 days after birth (BPD28) is associated with wheezing disorders. METHODS This was a multicentre retrospective cohort study of population data from infants (body weight

Bubbly/cystic appearance on chest radiograph is an important factor in severe-type bronchopulmonary dysplasia (BPD) in Japan. The aim of this study was to determine the perinatal characteristics and neonatal complications of the bubbly/cystic(+) group in extremely preterm infants with BPD, that is, oxygen dependency at day 28 after birth (BPD28).This was a multicenter retrospective cohort study of population data from infants (birthweight,1,500 g) enrolled in the Neonatal Research Network of Japan. Of the 15 480 infants born at28 weeks' gestational age (GA) between 2003 and 2012, 8,979 met the BPD28 criteria. The BPD28 infants were classified according to bubbly/cystic appearance on radiograph (±) at28 postnatal days.The bubbly/cystic(+) group had lower GA and birthweight and required longer mechanical ventilation and oxygen dependency than the bubbly/cystic(-) group. After adjustment for confounding factors, bubbly/cystic appearance was an independent risk factor for home oxygen therapy at discharge.Bubbly/cystic appearance on chest radiograph was a predictor of short-term respiratory outcomes in infants with BPD28, which is diagnosed much earlier (≥28 postnatal days), and has a potentially different etiology to BPD36 (oxygen and/or positive pressure respiratory support dependency at 36 weeks' postmenstrual age).

This report describes the case of a very low-birth-weight male infant with neonatal lupus erythematosus. His mother had Sjögren's syndrome, and her previous child had suffered a complete heart block. Accordingly, maternal steroid (betamethasone) therapy was administered to prevent a congenital heart block for 15 weeks (from 13 to 27 weeks' gestation). At 28 weeks' gestation, the mother was weaned off the steroid therapy, and an emergency cesarean section was carried out at 29 weeks and 6 days' gestation because of a nonreassuring fetal status (NRFS). At birth, the infant exhibited grade-III intraventricular hemorrhage (IVH). Although it is unclear why the infant developed a NRFS and IVH, the condition of the fetus should be carefully monitored during and after long-term maternal steroid treatment.

Purpose: We examined the relationship between fecal occult blood test (FOBT) screening behavior and beliefs regarding FOBT screening in order to formulate effective measures to improve FOBT screening rates. Method: In June 2010, we conducted a cross-sectional questionnaire survey of 600 randomly selected individuals aged 40–60 years who were registered participants of Refine, which was an internet research company to cooperate with this study. We assessed CRC knowledge, perceived risk of CRC, perceived severity of CRC, concern for CRC, beliefs of FOBT screening, FOBT screening behavior, and demographic variables. Result: There were 592 valid responses (from 294 males and 298 females; mean age 53.96 ± 8.39) in the final analysis. A total of 266 (44.9%) underwent FOBT in the year preceding the survey. Factor analysis relating to the beliefs of obtaining FOBT demonstrated five factors (α = 0.829) including: (1) perceived barrier, (2) subjective norms, (3) low importance, (4) descriptive norms, and (5) non-ne...

A series of indazole derivatives were identified as Sirt 1 activators though high-throughput screening. Optimization of each substituent on the indazole ring led to the identification of compound 13. Compound 13 appeared to give the best Sirt 1 activity of the compounds tested and also showed osteogenesis activity in a cell assay. Sirt 1 activators are therefore potential candidates for the treatment of osteoporosis.

We examined the predictive validity of a segmentation strategy based on intention and cancer worry for mammography adoption and explored key factors for promoting mammography adoption in each segment. A questionnaire survey was completed by 641 women aged 40-59 years. Among them, 559 answered a follow-up survey after 15 months. They were categorized into five segments: maintenance group (S5), higher implementation intention group (S4), higher goal intention group (S3), higher worry group (S2), or lower worry group (S1). The odds of participants in each segment adopting mammography during the follow-up period were calculated. Logistic regression analysis was conducted to identify psychological predictors (five attitudes to mammography and perceived health competence) of transition to upper segments (S1 vs. S2, S2 vs. S3, S3 vs. S4, S4 vs. S5). Compared to S5, other segments did not undertake mammography at significant rates during the follow-up. The following were significant predictors for inclusion in upper segments: Lack of importance and perceived health competence were associated with inclusion in S2; lack of importance and barriers to screening were associated with inclusion in S3; perceived health competence was associated with inclusion in S4; and lack of importance was associated with inclusion in S5. These results confirm the predictive validity of a segmentation strategy, and indicate that there might be specific key factors for each segment in promoting mammography adoption.

Objectives This study aimed to develop a structural model for mammography adoption in Japanese middle-aged women by using constructs from the transtheoretical model (TTM), the theory of planned behavior (TPB), implementation intentions, and cancer worry. Methods Questionnaires based on items including TTM, TPB, implementation intentions, cancer worry-related variables, and demographic variables were distributed to 1000 adult women aged 40 to 59 years, with 641 subjects being used in the final analysis (response rate = 64.1%). Results Regarding the stage of adoption, 79 participants (12.3%) were at the precontemplation stage, 30 (4.7%) were at the relapse stage, 142 (22.2%) were at the contemplation stage, 88 (13.7%) were at the action stage, and 302 (47.1%) were at the maintenance stage. Our model, derived from structural equation modeling, revealed that the stage of mammography adoption was significantly affected by goal intentions, implementation intentions, perceived barriers, history of breast cancer screening, and relative risk. A logistic regression analysis revealed that goal intentions and implementation intentions significantly predicted mammography uptake within 1 year. Conclusion This study developed an integrated model constructed from TTM, TPB, implementation intentions, and cancer worry to account for mammography adoption in Japan, and also confirmed the predictive validity of the model. Copyright © 2013 John Wiley & Sons, Ltd.

Collapsin response mediator protein2 (CRMP2) is a brain-specific protein involved in neuronal polarity and axonal guidance, and phosphorylation of CRMP2 regulates the function and the activity. CRMP2 has shown to be implicated in several neurodegenerative diseases (Alzheimer's disease, epilepsy and ischemia) and this study was designed to assess the role of CRMP2 in periventricular leukomalacia (PVL). We developed a PVL model using 3-day-old rats to investigate the expression and phosphorylation of CRMP2 in the newborn brain. Hypoxia-ischemia was applied by unilateral carotid ligation followed by exposure to 5% oxygen for 30min. Pathological changes were evaluated from 0h to 21d post-HI, and white matter damage including severe necrosis, white matter rarefaction and lateral ventricle dilatation were found. In the PVL model astrogliosis and axonal damage were detected in the injured white matter by immunohistochemistry at 48-168h post-HI, and delayed myelination was verified by Western blotting after 21-day post-HI. We confirmed that this model showed neuropathological features of PVL. Next, significant changes of CRMP2 were observed in the brain of the PVL model. Western blotting and immunohistochemistry showed that cleavage and hypo-phosphorylation of CRMP2 occurred after 48h post-HI in the PVL brain. Our results suggest that cleaved CRMP2 could represent hypo-phosphorylated-CRMP2 and HI could induce activation of CRMP2 in the PVL brain. The activated CRMP2 may play an important role in neuronal plasticity in PVL. Our findings suggest that future treatment strategies of PVL should target the phosphorylation mechanism of CRMP2.

The purpose of this study was to examine the feasibility of a physical activity intervention program and the relationship between physical activity and psychological adjustment in Japanese advanced lung cancer patients in chemotherapy. The study was designed as an intervention study and the sample was comprised of advanced lung cancer patients in chemotherapy, all of whom provided written informed consent. Physical activity was recorded by uniaxial accelerometry monitors (Lifecoder®, Suzuken, Co., Ltd), and psychological adjustment was measured by the Hospital Anxiety and Depression Scale (HADS). Each participant received 1) feedback about the data of their footsteps, 2) positive reinforcement for being physically active, 3) enhancement of autonomy for being physically active and 4) information about setting goals related to physical activity in the first, second, and fourth week. Drop out rate of participants was 33.3% (3/9). None of the variables changed over the four weeks of the study. Spearman's correlational analysis revealed that higher steps were correlated with lower depression (r= −.90, p

The purpose of this study was to examine the influence of short-term affect resulting from a physical education class on long-term affect and self-efficacy for exercise. Thirty-seven male university students who attended a physical education class were recruited as participants. The class was conducted once a week for twelve weeks, and four evaluation scales were used: The Waseda Affect Scale of Exercise and Durable Activity (WASEDA), the Feeling Scale (FS), which is an affect scale for assessing the acute affects of exercise, the Japanese version of the Positive and Negative Affect Schedule (PANAS) to assess long-term affect, and the self-efficacy for exercise scale to assess the self-efficacy of maintaining exercise behavior. The participants rated the WASEDA and the FS at the end of each class session, and then we calculated the average score of each affect for these two scales. They responded to the PANAS and the self-efficacy for exercise scale at the end of the whole physical education program. It was found that Positive Affect as rated by the PANAS after the class was related to the average score for Positive Engagement. Furthermore, the average score for Positive Engagement was related to self-efficacy for exercise after the class. On the other hand, the average score for Negative Affect (WASEDA), Tranquility, and Pleasantness was not related to long-term affect or exercise self-efficacy after the class. In conclusion, the present study identified the importance of positive engagement in a physical education class. Future studies should explore the exercise prescription for obtaining activated and positive engagement along with acute exercise.

This study examined the application of the trans-theoretical model (TTM) for readiness for decision-making of outpatient chemotherapy of Japanese advanced lung cancer patients by a cross sectional questionnaire survey. A questionnaire was conducted with 105 Japanese patients diagnosed with advanced lung cancer receiving chemotherapy. We classified them according to the TTM stages, including 4 in precontemplation, 42 in contemplation, 22 in preparation, and 35 in action. The valid model (chi(2) (37) = 42.56, p = 0.24; GFI = 0.93; AGFI = 0.88; CFI = 0.98; RMSEA = 0.04; AIC = 100.56) derived from structural equation modeling (SEM) revealed that stage of outpatient chemotherapy was significantly affected mostly by decisional-balance (beta = 0.60, p < 0.001) and partially by time from the patient's house to the hospital (beta = -0.15, p < 0.10), and that decisional-balance was significantly affected by self-efficacy (beta = 0.48, p < 0.001) and nausea (beta = -0.23, p < 0.01). The findings from our study provided encouraging results for adopting the TTM in decision making for outpatient chemotherapy in Japanese cancer care and several clinical implications were obtained from the results.

The purpose of this study was to examine the effects of a physical education program matched to the stages of change for exercise of the transtheoretical model (TTM) in a group of male university students. The participants were 239 male university freshmen (121 students in the intervention group and 118 in the control group). Two tasks were assigned for the intervention group. The first was conducted during class time, and the participants completed the task based on behavioral science. In this task, the participants selectively worked their own stages of change for exercise. For participants at the precontemplation stage, we set assignments to clarify that they had a sedentary lifestyle. For participants at the contemplation stage, we set tasks to prompt them to think about the pros and cons of an active lifestyle. For participants at the preparation stage, we set tasks to produce rewards for achievement of their personal goals. For participants at the active stage, we set tasks to encourage the use of social support from people around them. For participants at the maintenance stage, we set tasks to encourage change in their environment to maintain a physically active lifestyle. The second assignment was a practical one conducted outside class time. This involved self-monitoring of daily physical activities. The participants were assessed for the stages of change for exercise, physical activity level, exercise self-efficacy, and decisional balance for exercise before and after attendance. The intervention group showed a greater increase in the scores for daily physical activity, and maintained their score for decisional balance to a better degree than the control group. Additionally, in the intervention group, the stages of change for exercise progressed significantly after attendance as compared with the control group.

The present study was aimed at exploring the barriers and facilitators of physical activity and exercise among the parents of children with intellectual disabilities. A qualitative study related to barriers and facilitators was conducted on 42 parents of children with intellectual disabilities through an open-ended questionnaire. Content analysis was performed by the KJ method (Kawakita, 1970), i.e., the barriers and facilitators of physical activity and exercise, by eight members. Consequently, 58 responses as barriers and 46 responses as facilitators were reported. Through the KJ method, nine items were categorized as barriers, and 10 as facilitators. In specific terms, the following items were categorized as barriers: “Too busy,” “Bad physical condition,” “To have to care for one's family,” “Not enough psychological status,” “Bad weather,” “Insufficient information,” “Not economically viable,” “Nowhere to exercise and conduct physical activity,” and “Nobody to do it with.” The following items were categorized as facilitators: “To have people to do it with,” “A good environment and weather,” “Time,” “To enhance one's athletic performance,” “To be fun,” “To have a goal,” “To feel good,” “Not to have care-giving obligations,” and “To have already paid for membership fees.” The results of our study show that the parents of children with intellectual disability should utilize their family members not as a barrier but as a facilitator. The results of this study are expected to be used as basic data to support parents' physical activity and exercise behavior.

Objectives: A psychometric scale for assessing cancer-related worry among cancer patients, called the Brief Cancer-Related Worry Inventory (BCWI), was developed. Methods: A cross-sectional questionnaire survey for item development was conducted of 112 Japanese patients diagnosed with breast cancer, and test–retest validation analysis was conducted using the data from another prospective study of 20 lung cancer patients. The questionnaire contained 15 newly developed items for cancer-related worry, the Hospital Anxiety and Depression Scale, The Impact of Event Scale Revised, and the Medical Outcomes Study Short Form-8. Results: Exploratory factor analysis of the 15 items yielded a 3-factor structure including (1) future prospects, (2) physical and symptomatic problems and (3) social and interpersonal problems. A second-order confirmatory factor analysis identified a second-order factor called cancer-related worry and confirmed the factor structure with an acceptable fit (chi-square (df=87)=160.16, P=0.001; GFI=0.83; CFI=0.92; RMSEA=0.09). The internal consistency and test–retest reliability were confirmed with the lung cancer sample. Multidimensional scaling found that cancer-related worry is separate from anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms. Conclusion: Our study succeeded in developing and confirming the validity and reliability of a BCWI. The study also confirmed the discriminable aspects of cancer-related worry from anxiety, depression, and PTSD symptoms. Copyright © 2008 John Wiley & Sons, Ltd.

A series of ponasterone A (PNA) derivatives with various steroid moieties were synthesized to measure their binding activity to the ecdysone receptors of Drosophila Kc cells. The activity of compounds was evaluated by determining the concentration required to give the 50% inhibition (IC 50 in M) of the incorporation of [ 3 H]PNA to Drosophila Kc cells. Compounds with no functional groups such as OH and C O group in the steroid skeleton moiety were inactive. By the introduction of functional groups such as the OH and the C O group in the steroidal structure, these compounds became active. Some compounds containing the A/B- trans ring fusion, which is different from that (A/B- cis ) of ecdysteroids were also active. The oxidation of CH 2 at 6-position to C O, enhanced the activity 19 times, but the activity was erased by the reduction of oxo to OH group at 6-position. The activity was enhanced about 250 times by the conversion of A/B ring configuration from trans [(20 R ,22 R )-2β,3β,20,22-tetrahydroxy-5α-cholestan-6-one: pIC 50 = 4.84] to cis [(20 R ,22 R )-2β,3β,20,22-tetrahydroxy-5β-cholestan-6-one: pIC 50 = 7.23]. The latter cis -type compound which is the most potent among compounds synthesized in this study was equipotent to the natural molting hormone, 20-hydroxyecdysone, even though it is 1/50 of PNA.

OBJECTIVE To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN We included 58 004 infants born weighing

Down syndrome with transient myeloproliferative disorder (TMD) is often associated with perinatal liver fibrosis. The authors recently encountered an autopsy case of this disease with a characteristic severe perisinusoidal liver fibrosis. Osteopontin (OPN) is a molecule that plays an important role in diverse fibro-inflammatory diseases. The purpose of the present report was to examine the involvement of OPN in development of the Down syndrome-associated liver fibrosis. Histology indicated severe perisinusoidal fibrosis and ductular arrangements of hepatocytes in the liver. Appearance of atypical megakaryocytes in the liver, a feature of TMD associated with Down syndrome, was not evident. On immunohistochemistry expression of OPN was observed in hepatocytes often having ductular arrangements and infiltrating macrophages. In contrast, a small number of transforming growth factor-beta1 (TGF-beta1)-positive mononuclear cells were present in the liver. Numerous activated hepatic stellate cells (HSC) expressing alpha-smooth muscle actin (alpha-SMA) were seen in the perisinusoidal area. A recent report indicated that OPN could directly activate the HSC. Thus, it is suggested that OPN produced by hepatocytes and macrophages induces activation of the HSC, and leads to the development of perisinusoidal liver fibrosis.

This study was conducted to examine the influence of a university physical education program on the volume of physical activity in male university students with disabilities. Three university freshmen who attended a health-related physical activity program (adapted course) participated in the study. Student A had diseases of the internal organs and a disabled right leg, student B had chronic nephritis, and student C had a chronic herniated intervertebral disc. As well as guidance or lectures, each class involved recording of attendance and measurement of body weight and fat (10 minutes), an assignment based on behavioral sciences and reflecting on a one-week self-monitored physical activity record (20 minutes), sports activities (45 minutes; e.g., boccia), and documenting the sports activities peformed (5 minutes). Students attending a class were challenged with two types of assignment. One was a class-practice assignment that included a component on behavioral sciences. The other assignment involved self-monitoring of a physical activity record for one week. In general, a tendency for an increase in the number of steps counted by a pedometer was observed throughout the 13 classes. Furthermore, self-efficacy and decisional balance for exercise also improved between pre- and post-attendance. Based on these results, it was concluded that the physical education program had a positive influence on the volume of physical activity of university students with disabilities.

The purpose of this study was to investigate the effects of physical education [PE] homework on the amount of daily physical activity and the health-related fitness of university freshmen. Two hundred and eighty four Japanese university freshmen were allocated to either homework group (N=133) or control group (N=151). The tasks for homework group were daily life (out of class) self-monitoring of physical activity to promote daily physical activity, as well as fitness tests and sports activity during the class. The tasks for control group were health-related fitness tests and sports activity during the class. The Physical Activity Assessment Scale (PAAS; Wakui & Suzuki, 1997), which consists of three subscales, was used to evaluate physical activity patterns of the participants. The three subscales were 1) Exercise/Sports: measures exercise/sports-related physical activities with more than moderate intensity, 2) Time Management: measures the ability of time management in being occupied and having little time for exercise/sports participation, and 3) Daily Activity: measures relatively light physical activities in daily life. Health-related fitness (cardiovascular endurance, muscle strength/endurance, flexibility, and body fat) was also measured. As the result of ANOVA, PE homework in daily life was found to increase; 1) the amount of physical activity widely with light to moderate intensity, 2) some healthrelated fitness related to practical homework. These results suggest that PE homework can contribute to promoting daily physical activity required for fitness program emphasized today.

A case of an infant with a rare combination of polysplenia syndrome with common atrioventricular canal and persistent truncus arteriosus is presented. In our present case, severe common atrioventricular valve regurgitation was identified, as in previous cases. To our knowledge, echocardiographic and autopsy findings of this association has not been previously reported. The persistent truncus arteriosus is extremely rare in the setting of the polysplenia syndrome, but the present case report demonstrates that these anomalies may, at times, occur.

Beckwith-Wiedemann syndrome (BWS) is the most common congenital overgrowth syndrome involving tumor predisposition. BWS is caused by various epigenetic or genetic alterations that disrupt the imprinted genes on chromosome 11p15.5 and the clinical findings of BWS are highly variable. Hyperinsulinemic hypoglycemia is reported in about half of all babies with BWS. We identified an infant with diazoxide-unresponsive congenital hyperinsulinism (HI) without any apparent clinical features suggestive of BWS, but diagnosed BWS by molecular testing. The patient developed severe hyperinsulinemic hypoglycemia within a few hours after birth, with macrosomia and mild hydronephrosis. We excluded mutations in the K(ATP) channel genes on chromosome 11p15.1, but found a rare homozygous single nucleotide polymorphism (SNP) of ABCC8. Parental SNP pattern suggested paternal uniparetal disomy in this region. By microsatellite marker analysis on chromosome 11p15, we could diagnose BWS due to the mosaic of paternal uniparental disomy. Our case suggests that some HI of unknown genetic etiology could involve undiagnosed BWS with no apparent clinical features, which might be diagnosed only by molecular testing.

We report a preterm infant who was prescribed an MCT formula and subsequently developed carnitine deficiency with liver dysfunction and an elevation of serum CK level. A male infant who had been born at 24 weeks' gestation with birth weight 799 g, was fed with an MCT formula containing 76.8% of all kinds of lipids, because of his steatorrhea after the 30th day. On the 100th day, he was noted hepatomegaly and elevation of serum levels of AST, ALT and CK. The needle biopsy of the liver indicated the existence of the liver damage. He showed low serum carnitine with high urinary loss of acylcarnitine and dicarboxylic aciduria. Administration of L-carnitine was an effective treatment. The carnitine deficiency might be exaggerated by an increased urinary loss of acylcarnitine. We should be cautious of the risk of carnitine deficiency in preterm infants during prolonged use of MCT formula.

A sister and a brother with 46, XX (46, XY), -21, +der (15) (q22.1; q22.1) mat were reported whose mother had a karyotype of 46, XX, t(15; 21)(q22.1; 22.1) and was phenotypically normal. Both sibs were mentally retarded and dysmorphic. Moreover, the sister had a holoprosencephaly with congenital hydrocephalus, and the brother showed congenital hydrocephalus.

Premature infants with intrauterine growth restriction (IUGR) are at greater risk for an adverse perinatal outcome. IUGR affects hepatocyte function, but the histopathological changes in the postnatal liver are not well known. We report a male infant with severe IUGR. His mother was transferred to our hospital at 26 weeks of gestation because of preterm labor and severe IUGR. An emergency cesarean section was carried out because of a non-reassuring fetal status. The birth weight of the infant was 332 g. He showed congestive heart failure and marked hepatomegaly from birth. After 1 week, blood examinations showed hyperbilirubinemia with high direct bilirubin. Because of liver dysfunction, he received the minimal total parenteral nutrition for 7 days. After 1 month, he progressively developed ascites and coagulopathy, and died 3 months after birth. Liver autopsy showed diffuse perisinusoidal fibrosis. Fibrosis was also prominent around the central vein. Immunohistochemical study revealed many alpha-smooth muscle actin-positive cells, which represent activated hepatic stellate cells, and a few transforming growth factor-beta1-positive cells in the perisinusoidal fibrotic area. These results indicate that the infant developed chronic (end stage) liver failure by 3 months of age. We excluded congenital infection, metabolic syndrome and citrin deficiency. It is therefore conceivable that intrauterine cardiac failure may be responsible for liver fibrosis. Early detection of liver dysfunction soon after birth is a key to predict the prognosis of severe IUGR in preterm infants.

Background: Transient hypothyroxinemia is the most common thyroid dysfunction in preterm infants. Hypothalamic–pituitary–thyroid immaturity and non-thyroidal illness contribute to its etiology. The aim of the present study was therefore to determine the relationship between thyroid hormone status and early postnatal steroid therapy in preterm infants. Methods: A prospective study of premature infants born at

A case of Down's syndrome associated with liver fibrosis is reported. The fibrosis was diffusely distributed along sinusoids, and an excess of megakaryocytes was also found in the liver. To determine the mechanism of liver fibrosis in Down's syndrome, we immunohistochemically stained the liver with markers of myofibroblast-like cells, antialpha smooth muscle actin antibodies and antidesmin antibodies. The myofibroblast-like cells were found along sinusoids, suggesting that liver fibrosis in Down's syndrome is caused by the myofibroblast-like cells derived from Ito cells/lipocytes. The expression of transforming growth factor (TGF)-beta1, which is an important mediator of theactivation of lipocytes, was immunohistochemically examined. The accumulation of TGF-beta1 was observed in cells in the sinusoidal spaces, which involve the intracellular expression of megakaryocytes. Together, these findings suggest that megakaryocyte-derived TGF-beta1 is one of the likely candidates in the lipocyte activation of liver fibrogenesis in Down's syndrome.

Background: Glucocorticoid hormones play an important role in architectural and biochemical lung maturation. Although much of the molecular mechanism of their action in the lung is not fully understood, glucocorticoids directly or indirectly regulate lung maturation. Indirect effects of glucocorticoids may involve the modulation of cell-cell or cell-matrix interactions. Fibronectin (FN) is the major constituent of the pulmonary extracellular matrix and exists in multiple isoforms arising from alternative RNA splicing. EIIIA is the major alternatively spliced segment, and its expression is regulated in a spatiotemporal and oncodevelopmental manner. Objectives: The present study focuses on the regulation of EIIIA-containing FN isoforms (referred to as EIIIA+ FN) by glucocorticoids in the developing lung. Methods: Dexamethasone (DEX) or saline was injected daily into pregnant rats from day 15 of gestation (term = day 22) until 24 h before sacrifice. The expression of EIIIA+ FN and proliferating cell nuclear antigen (PCNA), a biochemical marker for cell proliferation, was investigated in the fetal rat lung. Results: At day 20 of gestation (the canalicular stage), the DEX-treated lung showed a significant decrease in weight and saccular septal wall thickness, while the messenger RNA expression of the surfactant protein SP-B was increased in the DEX-treated lung, as compared with the control lung. The expression of EIIIA+ FN and PCNA around the distal airspaces was less extensive in the DEX-treated lung than in the control lung at day 20 of gestation. Conclusions: Given the finding in vitro that EIIIA+ FN regulated the cell cycle, our results suggest that the change of EIIIA+ FN expression in the DEX-treated lung affected pulmonary cell proliferation.

Fibronectin is known to regulate the development of the lung. The EIIIA segment of fibronectin is one of the major alternatively spliced segments and modulates the cell proliferative potential of fibronectin in vitro. But the specific role of the EIIIA-containing fibronectin isoform (referred to as EIIIA+ fibronectin) in pulmonary cell proliferation has not been explored in vivo as yet. In this study, to see whether EIIIA+ fibronectin is associated with pulmonary cell proliferation in vivo, the authors immunohistochemically examined the spatiotemporal relationship of the EIIIA+ fibronectin isoform protein and proliferating cell nuclear antigen (PCNA), a biochemical marker for the cell proliferation, during the alveolar formation in the developing rat lung. EIIIA+ fibronectin protein was localized in the epithelial cells and in the mesenchymal tissues. The expression of EIIIA+ fibronectin protein gradually decreased from the pseudoglandular stage to the saccular stage and then slightly increased from the saccular stage to the alveolar stage. This change in the EIIIA+ fibronectin expression seemed to be in accord with the change in the number of PCNA-positive cells in the distal pulmonary cells throughout the lung development. These results suggest that the expression of EIIIA+ fibronectin is associated with the distal pulmonary cell proliferation during the alveolar formation.

It remains difficult to predict, early enough to intervene effectively, the risk of the development of learning disabilities among extremely low birth weight (ELBW) infants (birth weights less than 1,000 g). We prospectively studied the relationship between dilatations of lateral ventricles of the cranial computed tomography (CT) scan taken at the postconceptional age of 40 weeks and learning disabilities in their school age. Using a computer digitizer, we measured the areas of ventricles on cranial CT scans. The mean area of lateral ventricles of the learning disabilities-suspected group was significantly larger than that of the control group (392.9 and 277.4 mm 2 , respectively; P P .01). There were no significant differences between the two groups in gestation, birth weight, physical measurements, and developmental quotients at early school age. The dilatation of the lateral ventricles assessed by cranial CT at the corrected term may be one of the first predictors of learning disabilities recognizable at early school age.

Choriocarcinoma occurring in a placenta and metastasizing to the fetus is quite rare. We describe here a case of such infantile choriocarcinoma, initially appeared as refractory anemia and rapidly metastasized to the liver, lungs, and brain. The placenta looked normal and was not submitted to histological examinations. Neither noninvasive nor invasive diagnostic methods (ultrasonography, computed tomography, magnetic resonance image, scintigraphy, and hepatic arteriography) gave any diagnostic information on the tumor. Liver biopsy was considered too risky due to a possible bleeding. Correct diagnosis was established only after the postmortem examination. Two months after the infant's death, we were informed that the mother was found having hepatic and pulmonary tumors. The importance of the maternal history and measurement of urinary human chorionic gonadotropin is emphasized for a rapid and correct diagnosis of infantile choriocarcinoma.