Impact of dog and/or cat ownership on functional constipation at 3 years of age: the Japan Environment and Children's study.

PURPOSE: This investigation assessed the impact of dog and/or cat ownership during infancy on the presence of functional constipation (FC) at 3 years of age. METHODS: The fixed data of 73,936 singleton births from a large national birth cohort study commencing in 2011 were used to identify FC as estimated by Rome III at 3 years of age. Multiple logistic regression analysis was employed to search for correlations between FC development and dog and/or cat ownership in early childhood. RESULTS: A total of 8,459 toddlers (11.6%) met the Rome III criteria for FC at 3 years of age. Overall, 57,264 (77.5%) participants had never owned a dog or cat. We identified 7,715 (10.4%) infant-period owners, 1,295 (1.8%) current owners, and 7,762 (10.5%) long-term owners. Multivariate analysis showed that infant-period ownership remained significantly associated with the risk of developing FC at 3 years of age after adjusting for covariates (adjusted OR [95% CI] 1.09 [1.01-1.19] based on non-ownership). CONCLUSIONS: This Japanese large nationwide survey uncovered a possible adverse effect of infant-period dog and/or cat ownership prior to 6 months of age on FC status at 3 years of age.

Targeted temperature management at 36°C is a risk factor for ventilator-associated pneumonia.

BACKGROUND: In contrast to the adult population, limited information is currently available on risk factors for ventilator-associated pneumonia (VAP) in children. Therapeutic hypothermia has been identified as a risk factor for the early onset of VAP in adults; however, the relationship between VAP and normothermia remains unclear. The present study investigated risk factors for VAP in children, with a focus on the deleterious effects of therapeutic normothermia on VAP. METHODS: We retrospectively investigated the clinical characteristics of children treated with mechanical ventilation for more than 48 h and analyzed risk factors for VAP. The endpoint was the onset of VAP by the seventh day after the initiation of mechanical ventilation. RESULTS: Among the 288 patients enrolled, seven (2.4%) developed VAP. No significant differences were observed in clinical backgrounds between the VAP and non-VAP groups. A univariate analysis identified target temperature management (TTM) at 36°C (p < 0.0001) and methylprednisolone (mPSL) pulse therapy (p = 0.02) as risk factors for VAP. An analysis of the time to the onset of VAP by the Kaplan-Meier plot and log-rank test revealed a significantly higher incidence of VAP in the TTM group (p < 0.0001) and mPSL pulse group (p = 0.001). CONCLUSION: TTM at 36°C and mPSL pulse therapy may be risk factors for VAP in the pediatric population.

Prospective cohort study for postnatal cytomegalovirus infection in preterm infants.

AIM: Cytomegalovirus (CMV) is a virus that can cause congenital and postnatal infections. Postnatal CMV is mainly transmitted via breast milk and blood transfusions. Frozen-thawed breast milk is used to prevent postnatal CMV infection. A prospective cohort study was conducted to determine the infection rate, risk, and clinical findings of postnatal CMV infection. METHODS: This prospective cohort study included infants born at 32 weeks or earlier than the gestational age (GA). Participants were prospectively screened for infection in the urine by performing urine CMV DNA tests twice, that is, once within the first 3 weeks of life and again after 35 weeks postmenstrual age (PMA). Postnatal CMV infection was defined as a case of CMV negative tests within 3 weeks of birth and CMV positive tests after 35 weeks PMA. CMV-negative blood products were used for transfusions in all cases. RESULTS: A total of 139 patients were subjected to two urine CMV DNA tests. The prevalence of postnatal CMV infection was 5.0%. One patient died of sepsis-like syndrome. The risk factors of postnatal CMV infection were younger GA and older age of the mother. The characteristic clinical findings of postnatal CMV infection were pneumonia. CONCLUSIONS: Frozen-thawed breast milk feeding is not fully effective in preventing postnatal CMV infection. The prevention of postnatal CMV infection is important to further improve the survival rate of preterm infants. Development of guidelines on breast milk feeding for the prevention of postnatal CMV infection is necessary in Japan.

Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy.

PURPOSE: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. METHODS: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. RESULTS: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. CONCLUSION: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.

High Incidence of Hippocampal Abnormalities in Pediatric Patients with Congenital Cytomegalovirus Infection.

BACKGROUND: Congenital cytomegalovirus (CMV) infection exhibits polymicrogyria, intracranial calcification, white matter lesions, and several types of intracranial lesions on magnetic resonance imaging (MRI), in addition to various developmental disorders and epilepsies. However, little is known on the presence of hippocampal abnormality in this affliction. The aim of this study is to clarify the incidence of hippocampal abnormality in congenital CMV infection. METHODS: Seventeen children diagnosed as having congenital CMV infection along with 17 age-matched pediatric controls were retrospectively evaluated by brain MRI and clinical review. The measurement data were obtained from conventional coronal sections in this retrospective study. Hippocampal malrotation (HIMAL) was defined as a hippocampal diameter ratio (i.e., the ratio of the height and width of the hippocampus) of >0.92. RESULTS: Hippocampal diameter ratios were significantly higher in the congenital CMV infection group (0.99 [range: 0.70-1.58] on the right side and 0.85 [range: 0.66-1.39] on the left side) than in controls (0.71 [range: 0.58-0.91] and 0.70 [range: 0.50-1.00], respectively). HIMAL was present in 17 of 34 hippocampi (50%) in the congenital CMV infection group and 1 of 34 hippocampi (2.9%) in controls. No correlations were detected between HIMAL and intelligence quotient/developmental quotient or the occurrences of autism spectrum disorder or epilepsy. CONCLUSION: This study is the first to demonstrate the incidence of hippocampal abnormality to be significantly higher in congenital CMV infection patients than in age-matched controls. Further study is necessary to clarify the associations of HIMAL with other clinical and developmental features.

Insufficient maternal gestational weight gain and infant neurodevelopment at 12 months of age: the Japan Environment and Children's Study.

Abnormal maternal gestational weight gain (GWG) increases the risk of obstetric-related complications. This investigation examined the impact of GWG on infant neurodevelopmental abnormalities at 12 months of age using the data of a nationwide Japanese cohort study. Questionnaire data were obtained from the ongoing Japan Environment and Children's Study cohort study. Maternal GWG was subdivided as below, within, or above the reference values of the Institution of Medicine pregnancy weight guidelines. The Ages and Stages Questionnaire, third edition (ASQ-3) is a parent-reported developmental screening instrument for children across five domains: communication, gross motor, fine motor, problem-solving, and personal-social. Multiple logistic regression analysis was employed to identify correlations between GWG and developmental delay defined as ASQ-3 scores of less than two standard deviations below the mean. A total of 30,694 mothers with singleton live births and partners who completed the questionnaire were analyzed. The prevalence of mothers below, within, and above the GWG guidelines was 60.4% (18,527), 32.1% (9850), and 7.5% (2317), respectively. We recorded 10,943 infants (35.7%) who were outliers in at least one ASQ-3 domain. After controlling for covariates, GWG below established guidelines was associated with a significantly higher risk of developmental delay for the communication (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.09-1.34), gross motor (OR 1.14, 95% CI 1.05-1.24), fine motor (OR 1.13, 95% CI 1.04-1.24), problem-solving (OR 1.09, 95% CI 1.01-1.18), and personal-social (OR 1.15, 95% CI 1.07-1.24) domains.Conclusion: This large survey revealed a possible deleterious effect of insufficient maternal GWG on infant neurodevelopment.Trial registration: The Japan Environment and Children's Study (JECS) was registered in the UMIN Clinical Trials Registry on January 15, 2018 (number UMIN000030786). What is Known: • Inappropriate maternal gestational weight gain may cause obstetric complications and adverse birth outcomes. • Excess maternal weight gain may result in gestational diabetes, hypertension, eclampsia, caesarean delivery, and macrosomia, while insufficient maternal weight gain has been associated with pre-term birth and small for gestational age. What is New: • This study provides important information on a possible adverse effect of insufficient maternal gestational weight gain on offspring neurodevelopment at 12 months of age. • Our findings indicate a need to reconsider the optimal body mass index and gestational weight gain for women desiring pregnancy.

Maternal alcohol consumption and risk of offspring with congenital malformation: the Japan Environment and Children's Study.

BACKGROUND: The association between fetal exposure to alcohol and congenital structural disorders remains inconclusive. The present study searched for relationships between maternal alcohol consumption during pregnancy and the risk of congenital malformations. METHODS: We evaluated the fixed dataset of a large national birth cohort study including 73,595 mothers with a singleton live birth. Information regarding the alcohol consumption of mothers was obtained from self-reported questionnaires. Physicians assessed for 6 major congenital malformations (congenital heart defects [CHDs], male genital abnormalities, limb defects, cleft lip and/or cleft palate [orofacial clefts (OFC)], severe brain abnormalities, and gastrointestinal obstructions) up to 1 month after birth. Multiple logistic regression analysis was performed to identify associations between maternal alcohol consumption during pregnancy and each malformation. RESULTS: The prevalence of maternal drinking in early pregnancy and until the second/third trimester was 46.6% and 2.8%, respectively. The onset of CHD was inversely associated with mothers who quit drinking during early pregnancy (OR 0.85, 95% CI 0.74-0.98). There was no remarkable impact of maternal drinking habit status on the other congenital malformations after adjustment for covariates. CONCLUSIONS: Maternal alcohol consumption during pregnancy, even in early pregnancy, displayed no significant adverse impact on congenital malformations of interest. IMPACT: This large-scale Japanese cohort study revealed that no teratogenic associations were found between maternal retrospective reports of periconceptional alcohol consumption and congenital malformations after adjustment for covariates. This is the first nationwide birth cohort study in Japan to assess the effect of maternal alcohol consumption during pregnancy on major congenital malformations. Our finding indicated that maternal low-to-moderate alcohol consumption during pregnancy, even in early pregnancy, displayed no significant adverse impact on congenital heart defects, male genital abnormalities, limb defects, orofacial clefts, severe brain abnormalities, or gastrointestinal obstructions.

Association between pesticide usage during pregnancy and neonatal hyperbilirubinemia requiring treatment: the Japan Environment and Children's Study.

BACKGROUND: Maternal exposure to pesticides during pregnancy may cause oxidative hemolysis leading to neonatal hyperbilirubinemia. This investigation examined for associations between maternal use of pesticides or repellents during pregnancy and neonatal hyperbilirubinemia requiring phototherapy. METHODS: We used the dataset from the Japan Environment and Children's Study, a large national birth cohort study registered from January 31, 2011 to March 31, 2014. The fixed data of 61,751 live births were used to evaluate the presence of neonatal hyperbilirubinemia and potential confounding factors. We employed multiple logistic regression analysis to identify correlations between the frequency of maternal pesticide or repellent use during pregnancy and clinically relevant neonatal hyperbilirubinemia. RESULTS: After controlling for confounding factors, there were significant associations between neonatal hyperbilirubinemia necessitating phototherapy and the frequent use of indoor insecticide spray (OR 1.21, 95% CI 1.05-1.38). For spray- or lotion-type insect repellents, an opposite relationship was observed (more than a few times a week: OR 0.70, 95% CI 0.61-0.81, up to a few times a month: OR 0.84, 95% CI 0.78-0.91). CONCLUSION: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents. IMPACT: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents. This is the first study examining the effects of maternal exposure to pesticides or repellents on clinically relevant neonatal hyperbilirubinemia using a dataset from a nationwide birth cohort study. This large-scale Japanese cohort study revealed that the frequent use of indoor insecticide spray during pregnancy may increase the risk of neonatal hyperbilirubinemia requiring treatment.

PIEZO2 deficiency is a recognizable arthrogryposis syndrome: A new case and literature review.

PIEZO2 encodes a mechanically activated cation channel, which is abundantly expressed in dorsal root ganglion neuron and sensory endings of proprioceptors required for light touch sensation and proprioception in mice. Biallelic loss-of-function mutations in PIEZO2 (i.e., PIEZO2 deficiency) were recently found to cause an arthrogryposis syndrome. Sixteen patients from eight families have been reported to date. Herein we report a new case, including detailed clinical characteristics and courses as well as comprehensive neurological features. The patient was a 12-year-old girl presenting with congenital multiple contractures, progressive severe scoliosis, prenatal-onset growth impairment, motor developmental delay with hypotonia and myopathy-like muscle pathology, mild facial features, and normal intelligence. Her neurological features included areflexia, impaired proprioception, and decreased senses. Neurophysiological examination revealed decreased amplitude of sensory nerve action potentials, absent H reflex, and prolongation of central conduction times. Clinical exome sequencing revealed a novel homozygous frameshift mutation in PIEZO2 (NM_022068: c.4171_4174delGTCA: p.Val1391Lysfs*39) with no detectable mRNA expression of the gene. PIEZO2 deficiency represents a clinical entity involving characteristic neuromuscular abnormalities and physical features. Next generation sequencing-based comprehensive molecular screening and extensive neurophysiological examination could be valuable for diagnosis of the disorder.

Nationwide survey on cerebrotendinous xanthomatosis in Japan.

Cerebrotendinous xanthomatosis (CTX) is likely to be underdiagnosed and precise epidemiological characteristics of CTX are largely unknown as knowledge on the disorder is based mainly on case reports. We conducted a nationwide survey on CTX to elucidate the frequency, clinical picture, and molecular biological background of Japanese CTX patients. In this first Japanese nationwide survey on CTX, 2541 questionnaires were sent to clinical departments across Japan. A total of 1032 (40.6%) responses were returned completed for further analysis. Forty patients with CTX (50.0% male) were identified between September 2012 and August 2015. The mean age of onset was 24.5 ± 13.6 years, mean age at diagnosis was 41.0 ± 11.6 years, and corresponding mean duration of illness from onset to diagnosis was 16.5 ± 13.5 years. The most common initial symptom was tendon xanthoma, followed next by spastic paraplegia, cognitive dysfunction, cataract, ataxia, and epilepsy. The most predominant mutations in the CYP27A1 gene were c.1214G> A (p.R405Q, 31.6%), c.1421G> A (p.R474Q, 26.3%), and c.435G> T (p.G145=, 15.8%). Therapeutic interventions that included chenodeoxycholic acid, HMG-CoA reductase inhibitor, and LDL apheresis reduced serum cholestanol level in all patients and improved clinical symptoms in 40.5% of patients. Although CTX is a treatable neurodegenerative disorder, our nationwide survey revealed an average 16.5-year diagnostic delay. CTX may be underdiagnosed in Japan, especially during childhood. Early diagnosis and treatment are essential to improve the prognosis of CTX.

Clinically diverse phenotypes and genotypes of patients with branchio-oto-renal syndrome.

Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchiogenic anomalies, hearing loss, and renal anomalies. The aim of this study was to reveal the clinical phenotypes and their causative genes in Japanese BOR patients. Patients clinically diagnosed with BOR syndrome were analyzed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA), array-based comparative genomic hybridization (aCGH), and next-generation sequencing (NGS). We identified the causative genes in 38/51 patients from 26/36 families; EYA1 aberrations were identified in 22 families, SALL1 mutations were identified in two families, and SIX1 mutations and a 22q partial tetrasomy were identified in one family each. All patients identified with causative genes suffered from hearing loss. Second branchial arch anomalies, including a cervical fistula or cyst, preauricular pits, and renal anomalies, were frequently identified (>60%) in patients with EYA1 aberrations. Renal hypodysplasia or unknown-cause renal insufficiency was identified in more than half of patients with EYA1 aberrations. Even within the same family, renal phenotypes often varied substantially. In addition to direct sequencing, MLPA and NGS were useful for the genetic analysis of BOR patients.

Comparison of the phenotypes of patients harboring in-frame deletions starting at exon 45 in the Duchenne muscular dystrophy gene indicates potential for the development of exon skipping therapy.

Exon skipping therapy has recently received attention for its ability to convert the phenotype of lethal Duchenne muscular dystrophy (DMD) to a more benign form, Becker muscular dystrophy (BMD), by correcting the open reading frame. This therapy has mainly focused on a hot-spot (exons 45-55) mutation in the DMD gene. Exon skipping of an entire stretch of exons 45-55 is an approach applicable to 46.9% of DMD patients. However, the resulting phenotype is not yet fully understood. Here we examined the clinical profiles of 24 patients with BMD resulting from deletions starting at exon 45. The Δ45-55 group ranged in age from 2 to 87 years; no mortality was observed, and one patient was ambulatory at 79 years of age. The age at which patients became wheelchair-bound in the Δ45-48 group (18-88 years old) was approximately 50 years. Cardiomyopathy was well controlled by pharmaceuticals in both deletion groups. In contrast, the Δ45-47 and Δ45-49 groups exhibited more severe phenotypes than those with other mutations: the age at which patients in the Δ45-49 group became wheelchair-bound was around 30-40 years. Our study shows that clinical severity differs between each hot-spot deletion.

Sudden improvement in ventricular repolarization abnormality after a short detraining period in an athlete.

We describe the case of a 17-year-old male soccer player with T-wave inversion in precordial leads in resting electrocardiography, which also disclosed sinus bradycardia, early repolarization, and increased QRS voltage. These findings strongly suggested cardiomyopathy. The patient's T-wave inversion disappeared during only 2 weeks of detraining, and it re-appeared 2 weeks after resumption of intensive training. This sudden change in electrocardiographic parameters over a short period helped in identifying the adolescent as having athlete's heart.

Differential roles of MMP-9 in early and late stages of dystrophic muscles in a mouse model of Duchenne muscular dystrophy.

Matrix metalloprotease (MMP)-9 is an endopeptidase associated with the pathogenesis of Duchenne muscular dystrophy (DMD). The precise function of MMP-9 in DMD has not been elucidated to date. We investigated the effect of genetic ablation of MMP-9 in the mdx mouse model (mdx/Mmp9(-/-)). At the early disease stage, the muscles of mdx/Mmp9(-/-) mice showed reduced necrosis and neutrophil invasion, accompanied by down-regulation of chemokine MIP-2. In addition, muscle regeneration was enhanced, which coincided with increased macrophage infiltration and upregulation of MCP-1, and resulted in increased muscle strength. The mdx/Mmp9(-/-) mice also displayed accelerated upregulation of osteopontin expression in skeletal muscle at the acute onset phase of dystrophy. However, at a later disease stage, the mice exhibited muscle growth impairment through altered expression of myogenic factors, and increased fibroadipose tissue. These results showed that MMP-9 might have multiple functions during disease progression. Therapy targeting MMP-9 may improve muscle pathology and function at the early disease stage, but continuous inhibition of this protein may result in the accumulation of fibroadipose tissues and reduced muscle strength at the late disease stage.

Dimethyl fumarate suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease by modifying the Nrf2-Keap1 pathway.

Dimethyl fumarate (DMF) is a modifier of the nuclear factor (erythroid-derived 2)-2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. DMF treatment in the effector phase significantly suppressed the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) both clinically and histologically. DMF treatment leads to an enhanced Nrf2 antioxidant response in TMEV-IDD mice. DMF treatment in the effector phase significantly suppressed the level of IL-17A mRNA. DMF is known to inhibit differentiation of T helper 17 (Th17) cells via suppressing NF-κB. Taken together, our data suggest that DMF treatment in the effector phase may suppress TMEV-IDD not only via enhancing the antioxidant response but also via suppressing IL-17A.

Elevation of neuron specific enolase and brain iron deposition on susceptibility-weighted imaging as diagnostic clues for beta-propeller protein-associated neurodegeneration in early childhood: Additional case report and review of the literature.

Beta-propeller protein-associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation (NBIA). BPAN is caused by mutations in an X-linked gene WDR45 that is involved in autophagy. BPAN is characterized by developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. Brain magnetic resonance imaging (MRI) shows iron deposition in the bilateral globus pallidus (GP) and substantia nigra (SN). Clinical manifestations and laboratory findings in early childhood are limited. We report a 3-year-old girl with BPAN who presented with severe developmental delay and characteristic facial features. In addition to chronic elevation of serum aspartate transaminase, lactate dehydrogenase, creatine kinase, and soluble interleukin-2 receptor, she had persistent elevation of neuron specific enolase (NSE) in serum and cerebrospinal fluid. MRI using susceptibility-weighted imaging (SWI) demonstrated iron accumulation in the GP and SN bilaterally. Targeted next-generation sequencing identified a de novo splice-site mutation, c.831-1G>C in WDR45, which resulted in aberrant splicing evidenced by reverse transcriptase-PCR. Persistent elevation of NSE and iron deposition on SWI may provide clues for diagnosis of BPAN in early childhood.

Decreased Aortic Elasticity in Children With Marfan Syndrome or Loeys-Dietz Syndrome.

BACKGROUND: The characteristics of aortic elasticity are unclear in children with connective tissue disorders (CTDs) such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), especially in those with a non-dilated aortic root (AoR). This study evaluated the aortic elasticity properties of pediatric MFS and LDS patients with either dilated or non-dilated AoR.Methods and Results:The 31 children with MFS or LDS were classified into dilated (Z score of AoR diameter ≥2.5; n=17) or non-dilated (Z score of AoR diameter <2.5; n=14) AoR groups and compared with controls. Using transthoracic echocardiography, we analyzed the aortic elasticity parameters of distensibility, strain, and stiffness index at the levels of the AoR, sinotubular junction, ascending aorta, and descending aorta. Aortic distensibility and strain were significantly lower in both test groups than in controls at the AoR level. The Z score of AoR diameter significantly correlated with aortic distensibility (R=-0.63, P<0.001), strain (R=-0.54, P=0.002), and stiffness index (R=0.52, P=0.002) in the patients' groups. Multivariate analysis revealed that aortic distensibility and the type of CTD were independently associated with AoR dilatation. CONCLUSIONS: Aortic elasticity at the level of the AoR may be decreased in children with MFS or LDS even before AoR dilatation progresses. Less aortic distensibility and CTD type are considered important parameters in estimating AoR dilatation in these patients. (Circ J 2016; 80: 2369-2375).

Successful treatment of arrhythmia-induced cardiomyopathy in an infant with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal-dominant tumor suppressor gene syndrome that is characterized by the development of distinctive benign tumors and malformations in multiple organ systems (N Eng J Med 355:1345-1356, 2006). Cardiac rhabdomyomas are intracavitary or intramural tumors observed in 50-70 % of infants with TSC but only cause serious clinical problems in a very small fraction of these patients (N Eng J Med 355:1345-1356, 2006; Pediatrics 118:1146-1151, 2006; Eur J Pediatr 153:155-7, 1994); most individuals have no clinical symptoms and their tumors spontaneously regress. However, despite being clinically silent, these lesions can provoke arrhythmias and heart failure (Pediatrics 118:1146-1151, 2006; Eur J Pediatr 153:155-7, 1994). CASE PRESENTATION: We here report the clinical findings of an infant suffering from TSC complicated with dilated cardiomyopathy (DCM) after the regression of cardiac rhabdomyomas. Although his tumors improved spontaneously, tachycardia and irregular heart rate due to frequent premature ventricular and supraventricular contractions persisted from the newborn period and were refractory to several medications. His cardiomyopathy was suspected to have been induced by the tachycardia or arrhythmia. We found carvedilol therapy to be safe and highly effective in treating the cardiomyopathy. To our knowledge, this is the first case report of TSC with DCM after regression of cardiac tumors and its successful treatment. CONCLUSION: The patient's clinical course suggests that careful life-long disease management is important, even in TSC patients without apparent symptoms.

Cross-sectional observation of the relationship of depressive symptoms with lifestyles and parents' status among Japanese junior high school students.

OBJECTIVES: Students' depressive symptoms might be related to their own risk factors and to their parents' status. The objective of this cross-sectional study was to examine the relationship of depressive symptoms with lifestyle variables and parents' psychological and socio-demographic status among Japanese junior high school students. METHODS: Of 477 students and their parents, 409 (85.7 %) students and 314 (65.8 %) parents participated in the study. Students answered self-reported questionnaire on depressive symptoms, their heights and weights, subjective stress, body dissatisfaction, lifestyles including sleep duration and extracurricular physical activity in school and other physical activity outside the school, and nutritional intake. Parents responded to questionnaire on depressive symptoms and socio-demographic status. RESULTS: The prevalence of depressive symptoms was 24.9 %. Students with depressive symptoms were more likely to have stress. Students in shorter and longer sleep duration groups were more likely to have depressive symptoms. The students with depressive symptoms had smaller amount of energy intake than did those without depressive symptoms. Multiple logistic regression analysis revealed significant relationships between students' depressive symptoms and some independent variables. Sex, subjective stress, "almost-never"-categorized extracurricular physical activity in school and other physical activity outside the school, and having a parent with depressive symptoms were significantly associated with students' depressive symptoms. CONCLUSION: Reducing mental stress and taking care of lifestyles, especially, "almost-everyday"-categorized extracurricular physical activity in school and other physical activity outside the school, may have benefits for students' mental health, and having a parent with depressive symptoms may be associated with students' depressive symptoms.

Activity-dependent changes in excitability of perirhinal cortex networks in vitro.

Rat brain slices comprising the perirhinal cortex (PC) and a portion of the lateral nucleus of the amygdala (LA), in standard medium, can generate synchronous oscillatory activity that is associated with action potential discharge and reflects the activation of glutamatergic and GABAergic receptors. We report here that similar synchronous oscillatory events are recorded in the PC in response to single-shock, electrical stimuli delivered in LA. In addition, we found that the latency of these responses progressively increased when the stimulus interval was varied from 10 to 1 s; for example, the response latency during stimuli delivered at 1 Hz was more than twofold longer than that seen during stimulation at 0.1 Hz. This prolongation in latency occurred after approximately 5 stimuli, attained a steady value after 24-35 stimuli, and recovered to control values 30 s after stimulation arrest. These frequency-dependent changes in latency continued to occur during NMDA receptor antagonism but weakened following application of GABAA and/or GABAB receptor blockers. Our findings identify a new type of short-term plasticity that is mediated by GABA receptor function and may play a role in decreasing neuronal network synchronization during repeated activation. We propose that this frequency-dependent adaptive mechanism influences the excitability of limbic networks, thus potentially controlling epileptiform synchronization.