Attentional differences in audiovisual face perception between full- and preterm very low birthweight toddlers.

AIM: To investigate whether rightward attention to the mouth during audiovisual speech perception may be a behavioural marker for early brain development, we studied very preterm and low birthweight (VLBW) and typically developing (TD) toddlers. METHODS: We tested the distribution of gaze points in Japanese-learning TD and VLBW toddlers when exposed to talking, silent and mouth moving faces at 12, 18 and 24 months (corrected age). Each participant was categorised based upon the area they gazed at most (Eye-Right, Eye-Left, Mouth-Right, Mouth-Left) per stimulus per age. A log-linear model was applied to three-dimensional contingency tables (region, side and group). RESULTS: VLBW toddlers showed fewer gaze points than TD toddlers. At 12 months, more VLBW toddlers than TD toddlers showed left attentional bias toward any one face; however, this difference in attention asymmetry receded somewhat by 24 months. In talking condition, TD toddlers showed right attentional bias from 12 to 24 months, whereas VLBW toddlers showed such bias upon reaching 24 months. Additionally, more TD toddlers than VLBW toddlers attended to the mouth. CONCLUSION: Delays in exhibiting the attentional bias for an audiovisual face or general faces displayed by typically developing children might suggest differential developmental timing for hemispheric specialisation or dominance.

Early temperament as a predictor of language skills at 40 months.

BACKGROUND: Mastering language involves the development of expressive and receptive skills among children. While it has been speculated that early temperament plays a role in the acquisition of language, the actual mechanism has not yet been explored. We investigated whether temperament at 18 months predicted expressive or receptive language skills at 40 months. METHODS: A representative sample of 901 children and their mothers who were enrolled and followed-up longitudinally in the Hamamatsu Birth Cohort for Mothers and Children study was included in the analysis. Child temperament was measured at 18 months using the Japanese version of the Early Childhood Behavior Questionnaire. Expressive and receptive language skills were measured at 40 months using the Mullen Scales of Early Learning. RESULTS: The multiple regression analysis, adjusting for potential confounders, suggested that higher motor activation (fidgeting) at 18 months was associated with lower expressive and receptive language skills at 40 months. Higher perceptual sensitivity was associated with higher expressive and receptive language skills at 40 months. CONCLUSIONS: Specific temperament at 18 months of age predicted the development of the child's expressive and receptive language skills at 40 months.

Not sleeping soundly in early infancy is not bad.

AIMS: This study sought to determine whether not sleeping soundly in early infancy predicted poor development. This complemented earlier studies of children aged 12 months or older. METHODS: Sleep/wake patterns of 35 Japanese infants (23 males) with a gestational age of 37< weeks were recorded at home using actigraphy. Families were registered with a laboratory-based database for infant research. Follow-up recordings were conducted at 3, 4, 6, 12, and 24 months. Crawling was rated by mothers at 12 months and used to create regular and irregular crawling groups. Temperament was scaled using the Japanese Infant Behaviour Questionnaire-Revised Questionnaire and the Japanese Early Childhood Behaviour Questionnaire. RESULTS: At 4 months, infants with regular crawling style had shorter night-time sleep than infants with irregular crawling style. However, at 12 months, the former had longer motionless sleep at night compared to the latter. Before 6 months, infants with regular crawling style showed lower sleep efficiency, especially during the day, compared to those with irregular crawling style. In addition, the amount of night-time active sleep at 3 and 4 months were positively correlated with day-time activity, but not at 6 months. CONCLUSION: Short fragmental sleep in early infancy did not always predict poor development.

Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas.

To predict the prognosis of neuroblastoma patients and choose a better therapeutic protocol, we developed a cDNA microarray carrying 5340 genes obtained from primary neuroblastomas and examined 136 tumor samples. We made a probabilistic output statistical classifier that provided a high accuracy in prognosis prediction (89% at 5 years) and a highly reliable method to validate it. Kaplan-Meier analysis indicated that the patients in an intermediate group defined by existing markers are divided by microarray into two further groups with 5 year survivals for 36% and 89% of patients (p < 10(-4)), i.e., with unfavorably and favorably predicted neuroblastomas, respectively. According to these results, we developed a gene subset chip for a clinical tool, for which our classifier exhibited 88% prediction accuracy.

Difficulty in disengaging from threat and temperamental negative affectivity in early life: a longitudinal study of infants aged 12-36 months.

BACKGROUND: Attention disengagement is reportedly influenced by perceiving a fearful facial expression even in the first year of life. In the present study, we examined whether individual differences in disengaging from fearful expressions predict temperamental negative affectivity. METHOD: Twenty-six infants were studied longitudinally at 12, 18, 24, and 36 months, using an overlap paradigm and two temperament questionnaires: the Japanese versions of the revised Infant Behavior Questionnaire and Early Childhood Behavior Questionnaire. RESULTS: The infants fixated significantly more frequently to fearful than to happy or neutral faces. The attentional bias to threat (i.e., the number of fixed responses on fearful faces divided by the total number of fixed responses on faces) at 12 months was significantly positively correlated with negative affect at 12 months, and its relations with negative affect measured later in development was in the expected positive direction at each age. In addition, a moderation analysis indicates that the orienting network and not the executive network marginally moderated the relation between early attentional bias and later fear. CONCLUSIONS: The results suggest that at 12 months, infants with more negative affectivity exhibit greater difficulty in disengaging their attention from fearful faces. We also found evidence that the association between parent-reported fear and disengagement might be modulated in the second year, perhaps because of the differences in temperamental control networks.

Attentional asymmetry in orienting and alertness and its relationship to temperament: A longitudinal study of infants aged 6-24 months.

Previous research suggests that difficulties in orienting to visual stimuli directed by the right hemisphere are related to parental reports of distress and may be an early sign of autism spectrum disorder (ASD). One possible reason for this difficulty is infants' ability to achieve high levels of alertness, which also depends on the right hemisphere. This study examines the relationship between phasic alertness and asymmetry in visual orienting in typically-developing 6-24-month-old infants using the overlap paradigm. Participants were given a spatially non-directive warning signal shortly before the onset of the peripheral target. The signal reduced latencies in both overlap and no-overlap conditions. No main effects of age and visual field or interaction were found. However, results confirm the negative association between temperamental soothability and disengagement difficulty toward the left visual field at 6 months. This is discussed from the viewpoint of early left visual field attentional bias in relation to social cognition.

Precursor-T lymphoblastic lymphoma after unrelated bone marrow transplantation in a patient with Fanconi anemia.

Lymphoid malignancies are rare in patients with Fanconi anemia (FA), particularly after bone marrow transplantation. A boy, who was diagnosed with FA at the age of 5; underwent successful bone marrow transplantation at the age of 11. One year later, he presented with fever and dry cough, and was found to have an anterior mediastinal tumor. Biopsy of the tumor revealed precursor-T cell lymphoblastic lymphoma. Human leukocyte antigen analysis confirmed that the tumor cells were derived from the patient's own cells. He received mild chemotherapy for lymphoma, but his condition deteriorated rapidly and he died from excessive chemotherapy-related toxicity. The literature contains no reports of successful chemotherapy for lymphoid tumors in patients with FA, and therefore, alternatives to chemotherapy should be considered in the treatment of such patients.

Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan.

BACKGROUND: Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in pediatric patients are relatively rare. PROCEDURE: We performed a retrospective analysis in patients with PTCL over an 18-year period (1991-2008). RESULTS: We could analyze clinical data in 21 patients with non-anaplastic PTCL; 10 were female and 10 male. Median age of onset was 11 years (range: 1-21 years). There were nine patients with PTCL, not otherwise specified (PTCL-NOS); ten with extranodal NK/T-cell lymphoma, nasal type; one with angioimmunoblastic T-cell lymphoma; and one with subcutaneous panniculitis-like T-cell lymphoma. Initial lesions involved cervical lymph nodes in five patients, and the skin in five patients. In five patients, hemophagocytic syndrome (HPS) was the initial clinical feature. There were 12 patients with advanced stage disease (stages III and IV). Chemotherapy and radiation was administered in 18 and 2 patients, respectively. Among the two patients who did not receive chemotherapy and radiation, one patient died while being treated for HPS but another improved spontaneously. Although 5 patients relapsed, 18 of 21 patients remained alive without disease at last follow-up. Five-year overall survival rate was 85.2%. CONCLUSIONS: Generally, the outcome results of conventional chemotherapy for high-risk PTCL are poor in adult patients. However, the excellent results in our study suggest that PTCL of childhood is quite different from that of adulthood. Although this study is first report about PTCL of Asian children, the number of patients was small in this study. Larger studies are needed to confirm these findings.

Living donor liver transplantation for hepatoblastoma with Beckwith-Wiedemann syndrome.

BWS is one of the most well-known somatic overgrowth syndromes, which is characterized by macroglossia, organomegaly, abdominal wall defects, and predisposition to embryonal tumors, such as Wilms' tumor, hepatoblastoma, and adrenocortical carcinoma. We report a case of BWS in a girl with unresectable hepatoblastoma, who received a planned LVDT following neo-adjuvant chemotherapy. This is the first case report of liver transplantation for patients with BWS. Tumor surveillance after transplantation would be necessary to detect possible recurrence of the original disease and development of other malignancies.

Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor.

NICCD is an autosomal recessive genetic disorder, characterized by cholestasis, coagulopathy, hypoglycemia, fatty liver and multiple amino acidemia. NICCD develops in the neonatal/infantile period and has been reported as a "naturally curable" disease within one yr of life. Recently, we experienced an infantile NICCD who developed progressive liver failure, and required subsequent LT using a heterozygote living donor at eight months of age. Diagnosis of NICCD was established before transplantation, and donor evaluation included mutation in the SLC25A13 gene for exclusion of individuals with citrin deficiency citrullinemia. LDLT, from blood type identical mother using a left lateral segment graft, was performed without serious complication. Plasma amino acid concentration was normalized rapidly, and the patient was discharged 30 days after transplant. During one yr follow up, the recipient has been doing well without additional medication for NICCD. NICCD should be considered in the differential diagnosis as a cause of neonatal/infantile cholestatic disease. LT using a heterozygote living donor is an effective alternative in countries where a deceased donor is not available.

Vaginal yolk sac (endodermal sinus) tumors in infancy presenting persistent vaginal bleeding.

Vaginal yolk sac (endodermal sinus) tumors were diagnosed in two girls (ages 12 and 46 months). In both, the only manifestation was persistent vaginal bleeding. Pelvic ultrasonography, computed tomography, and magnetic resonance imaging revealed solitary vaginal masses (diameter, 5 and 2 cm, respectively). Serum alpha-fetoprotein was highly elevated in one patient and normal in the other. Biopsy was performed in the first patient, and a tumor excision, in the second. Combination chemotherapy with cisplatin, etoposide, and bleomycin or carboplatin was administered to the first patient, and shortly thereafter, the tumor size decreased by more than half; serum alpha-fetoprotein was normalized after four chemotherapy cycles. After chemotherapy, magnetic resonance imaging revealed a small residual lesion, however the second biopsy revealed no viable tumor cells. In the second patient, no visible tumor was observed after chemotherapy by vaginoscopy. Both patients are well at 19 and 14 months after diagnosis, respectively.

T cell-mediated control of Epstein-Barr virus infection in humanized mice.

Humanized NOD/Shi-scid/interleukin-2Rgamma(null) (NOG) mice with full T cell development had significantly longer life span after Epstein-Barr virus (EBV) infection, compared with those with minimal T cell development. Removing CD3(+) or CD8(+) T cells from EBV-infected humanized mice by administration of anti-CD3 or anti-CD8 antibodies reduced their life span. CD8(+) T cells obtained from EBV-infected mice suppressed the outgrowth of autologous B cells isolated from uninfected mice and inoculated with EBV in vitro. These results indicate that humanized NOG mice are capable of T cell-mediated control of EBV infection and imply their usefulness as a tool to evaluate immunotherapeutic and prophylactic strategies for EBV infection.

Living donor liver transplantation for glycogen storage disease type Ib.

Glycogen storage disease type 1b (GSD-1b) is due to an autosomal recessive inborn error of carbohydrate metabolism caused by defects in glucose-6-phosphatase translocase. Patients with GSD-1b have severe hypoglycemia with several clinical manifestations of hepatomegaly, obesity, a doll-like face, and neutropenia. Liver transplantation has been indicated for severe glucose intolerance. This study retrospectively reviewed 4 children with a diagnosis of GSD-1b who underwent living-donor liver transplantation (LDLT). Between November 2005 and June 2008, 96 children underwent LDLT with overall patient and graft survival of 92.3%. Of these, 4 (4.2%) were indicated for GSD-1b. All patients are doing well with an excellent quality of life because of the stabilization of glucose intolerance, decreased hospital admission, and normalized neutrophil count. LDLT appears to be a feasible option and is associated with a better quality of life for patients with GSD-1b. Long-term observation may be necessary to collect sufficient data to confirm the efficacy of this treatment modality.

Liver transplantation in a patient with propionic acidemia requiring extra corporeal membrane oxygenation during severe metabolic decompensation.

LDLT is an effective treatment modality in patients with congenial metabolic liver disease. PA is a rare autosomal recessive disorder caused by deficiency in propionyl-CoA carboxylase. The present study demonstrates a two-yr-old girl with PA who was admitted for metabolic decompensation and immediately treated with CHD and protein intake restriction at 46 days of age. Two yr later, the patient was readmitted for severe metabolic decompensation with complete atrioventricular block and ventricular fibrillation. CHDF and ECMO were indicated because of progressive metabolic and cardiac deterioration. After full recovery of the ejection fraction, planned LDLT was performed to prevent further metabolic decompensation and fatal cardiac insufficiency. No significant events occurred after the operation and the condition of the patient is stable with continued protein restriction and carnitine supplementation.

Analysis of the vitreous membrane in a case of type 1 Stickler syndrome.

BACKGROUND: Stickler syndrome causes ocular abnormalities, including retinal detachment and vitreoretinal degeneration, and systemic anomalies such as arthritis and deafness. Although retinal detachment is characteristic of this syndrome, the pathogenesis is unknown. CASE REPORT: A 10-year-old boy reported decreased vision and presented 5 days after visual loss. RESULTS: Ophthalmoscopy showed a retinal detachment with a giant tear in the right eye, and a nonpigmented epithelial detachment with pars plicata breaks in the left eye. Bilateral findings included an empty vitreous and a vitreous membrane at the equator. The systemic abnormalities included short stature and joint hypermobility. The diagnosis was type 1 Stickler syndrome, and the eyes were treated surgically. Immunohistochemistry showed that the vitreous membrane resected intraoperatively was comprised primarily of Müller cells. Electron microscopy showed dense collagen fibers around the cells in the membrane that were identical to the vitreous collagen inserted into the basement membrane of the cells, which was similar to the ultrastructure of the vitreous base. CONCLUSION: Müller cells might be primary components of the vitreous membrane in type 1 Stickler syndrome. The vitreoretinal interface, which resembled the ectopic vitreous base, in the vitreous membrane may be related to the pathogenesis of the retinal detachment.

Early development of attentional disengagement and phasic alertness.

Attention development is a critical foundation for cognitive abilities. This study examines the relationship between phasic aspects of alertness and disengagement in infants, using the overlap paradigm. Research shows that visual disengagement in overlap condition is modulated by auditory cues in 6-year-olds. Our participants were aged 6 months (N = 20), 12 months (N = 27), and 24 months (N = 14). Phasic alertness during overlap and no-overlap tasks was manipulated using a spatially nondirective warning signal shortly before onset of the peripheral target. Responses in overlap condition were slower and fewer than in no-overlap condition. The signal showed a tendency to reduce latencies in both overlap and no-overlap conditions. While our hypothesis that the warning signal might be more effective in younger infants was not supported, we confirmed the association reported in previous studies between temperamental soothability and disengagement latencies in infancy.

Attentional bias assessed by a facial expression cuing paradigm in infants.

To disambiguate infants' attentional bias towards fearful facial expressions, we applied a facial expression cueing paradigm to 36 6-month-old and 33 12-month-old infants, with 21 infants taking part at both ages. Infants made saccades towards a peripheral target preceded by a happy, fearful, or neutral cue directing their attention to the target location (congruent) or the wrong location (incongruent). The results show that infants were faster to respond when shown a fearful (vs. happy) face as a congruent cue, which is consistent with previous studies referring to fearful vigilance, while an incongruent fearful cue reduces attention shifts to the target on the opposite side of the monitor to a greater extent than an incongruent happy cue at 12 months, implying that a fearful facial expression prolongs attentional disengagement or is associated with a greater narrowing of attention. Additionally, the latencies of 6-month-olds were significantly faster than those of 12-month-olds in a congruent condition. The relationship between attentional bias and temperamental disposition was examined using the Infant Behavior Questionnaire-Revised. High temperamental orienting scores partly correlated with attentional bias at 12 months. The contributions of attentional brain networks to socio-cognitive and emotional development are also discussed.

Progression of hearing loss and choice of hearing aids by patients in their 60s, 70s, and 80s and older: experience in the Japanese super-aged era.

Background: Demographic data of patients with sensorineural hearing loss (SNHL) in super-aged societies are still limited.Aims/objectives: To report audiometric statistics of SNHL and hearing aid (HA) use in patients in their 60s, 70s, and 80s and older during the super-aged era.Material and methods: Medical charts and audiograms of 2064 older patients with SNHL who visited a Japanese University Hospital in 2007-2018 were retrospectively reviewed. Among 270 patients referred to the HA service unit (HASU), the percentage of final decisions to continue using HAs was calculated.Results: The average pure tone thresholds on initial visit to the clinic were 56.9, 60.6, 69.4, and 82.4 dB HL in patients in their 60s, 70s, 80s, and 90s, respectively. The rates of progression were 0.25, 0.87, 1.19, and 1.37 dB/year in patients in their 50s, 60s, 70s, and 80s, respectively. The percentage of patients in HASU who chose to use HAs did not differ among the 60s (59.3%), 70s (51.2%), and 80s and older (58.2%).Conclusions and significance: The clinical picture of patients with SNHL in their 70s and 80s differs because progression accelerates exponentially through these ages. HAs can be recommended to older adult patients in all the age groups.

Cohort profile: Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A).

PURPOSE: Effects of fetal, perinatal and childhood environment on the health of children at birth and during later life have become a topic of concern. The Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A) is an ongoing birth cohort of pregnant women and their children which has been used to provide unique data, as adjunct studies of JECS, on multifaceted potential factors affecting children's health. PARTICIPANTS: The JECS-A is part of the JECS which follows a total of 100 000 pairs of children and their mothers (fathers' participation is optional) across 15 regions in Japan. In JECS-A, of the 8134 pregnant women living in Ichinomiya City and Nagoya City, Japan, a total of 5721 pregnant women and their 5554 children were included. Sociodemographic and psychological data as well as biological specimens were collected from the pregnant women and their spouses (if available) in the cohort during their pregnancy. Information on children included in the JECS-A was collected from their mothers and includes demographic, behavioural, childcare, psychological and psychiatric data. Urine extracted from disposable diapers and anthropometric data were also obtained from the children. FINDINGS TO DATE: A similar distribution trend for age at delivery was confirmed between the pregnant women enrolled in the JECS-A and the national statistics of the relevant areas. However, differences in education level and household income were observed. A total of 5502 children remained in the cohort at 18 months after delivery. Compared with the national statistics, the basic demographics of the children in the cohort represented the population in the study areas. FUTURE PLANS: The enrolled children in the JECS-A will be followed until the age of 13 years. The studies that come from JECS-A will complement JECS and bring novel results with a high level of generalisability.

Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome 11q23, is downregulated in unfavorable neuroblastoma without promoter hypermethylation.

Although it has been well documented that loss of human chromosome 11q is frequently observed in primary neuroblastomas, the smallest region of overlap (SRO) has not yet been precisely identified. Previously, we performed array-comparative genomic hybridization (array-CGH) analysis for 236 primary neuroblastomas to search for genomic aberrations with high-resolution. In our study, we have identified the SRO of deletion (10-Mb or less) at 11q23. Within this region, there exists a TSLC1/IGSF4/CADM1 gene (Tumor suppressor in lung cancer 1/Immunoglobulin superfamily 4/Cell adhesion molecule 1), which has been identified as a putative tumor suppressor gene for lung and some other cancers. Consistent with previous observations, we have found that 35% of primary neuroblastomas harbor loss of heterozygosity (LOH) on TSLC1 locus. In contrast to other cancers, we could not detect the hypermethylation in its promoter region in primary neuroblastomas as well as neuroblastoma-derived cell lines. The clinicopathological analysis demonstrated that TSLC1 expression levels significantly correlate with stage, Shimada's pathological classification, MYCN amplification status, TrkA expression levels and DNA index in primary neuroblastomas. The immunohistochemical analysis showed that TSLC1 is remarkably reduced in unfavorable neuroblastomas. Furthermore, decreased expression levels of TSLC1 were significantly associated with a poor prognosis in 108 patients with neuroblastoma. Additionally, TSLC1 reduced cell proliferation in human neuroblastoma SH-SY5Y cells. Collectively, our present findings suggest that TSLC1 acts as a candidate tumor suppressor gene for neuroblastoma.