Development of literacy skills for Japanese deaf and hard-of-hearing children.

We compared the reading development of 77 deaf and hard-of-hearing (DHH) Japanese children, aged 5-7 (40 females), with 139 of their hearing peers (74 females) in 2018. We assessed each group's phonological awareness (PA), grammar, vocabulary, and reading of hiragana (Japanese orthography children learn first). DHH children showed significant delays in grammar and vocabulary but only a slight delay in PA. Younger DHH children scored better than their hearing peers in reading. Although PA predicted reading for hearing children, reading predicted PA for DHH children. PA partially explained grammar skills for both groups. The results suggest educational intervention for reading acquisition should be based on not only general linguistic features but also each language's unique characteristics.

Epidemiological study of oral allergy syndrome in birch pollen dispersal-free regions.

BACKGROUND: Oral allergy syndrome (OAS) is an immediate allergy caused by a cross-reaction of highly homologous common antigens (pan-allergens) contained in fruits/vegetables and pollen. METHODS: A questionnaire was provided to 6824 outpatient visitors and serum levels of specific IgEs against crude antigens and pan-allergen components were measured to study the relationship between the prevalence of OAS and pollinosis in the Fukui Prefecture where there is almost no dispersal of birch pollen. RESULTS: The prevalence of OAS was 10.8%. The rate of pollinosis complication in the OAS group was 67.4%, and OAS was observed in 16.8% of pollinosis patients. Causative foods in order of frequency were melon, pineapple, kiwi fruit, peach, and apple. A significantly higher number of patients from the OAS group were positive for birch, alder, and timothy grass-specific IgE. The rate of positivity for anti-component IgE corresponding to pollen in OAS group was also significantly higher. Of 34 patients with OAS caused by eating apples, 28 (82.4%) were positive for Mal d1-specific IgE. Of the 52 patients with peach-induced OAS, 41 (78.8%) were positive for Pur p1-specific IgE. The concordance rates between crude antigen-specific IgE and anti-PR-10 component-specific IgE were 87.1% and 93.3% for apple and peach respectively. CONCLUSIONS: In regions where birch pollen is not dispersed, OAS patients have a significant association with the onset of Bet v1-associated allergy. Anti-PR-10 component IgE was useful in diagnosing OAS, and crude antigen-specific IgE was also associated with apple and peach allergies.

Vocabulary and Grammar Differences Between Deaf and Hearing Students.

The present study investigated the development of literacy skills of deaf and hard-of-hearing (DHH) children in Japan. The three components of literacy, vocabulary, orthographic knowledge, and grammatical knowledge were assessed by using the subtests of the Adaptive Tests for Language Abilities (ATLAN), based on the item response theory developed by the authors). The participants consisted of 207 DHH children (first through twelfth grades) in Study 1, and 425 hearing children (first through sixth grades) in Study 2. The findings show that more than 80% of DHH children's vocabulary variance was explained by the other two componential skills, while the three tasks' difficulty was different. More specifically, their vocabulary and especially, their grammar lagged behind those of hearing children, whereas the difference between the two groups on kanji (one of the three orthographic systems in Japanese taught during the school years) was less. Although considerably delayed, their pattern of responses in grammar was similar to that predicted from normative data. Effective instruction for DHH children's literacy skills was generally discussed.

Long-term sublingual immunotherapy for Japanese cedar pollinosis and the levels of IL-17A and complement components 3a and 5a.

Allergen-specific immunotherapy is the only treatment that can alter the natural course of allergic disease. We performed long-term sublingual immunotherapy (SLIT) for patients with seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JCP), screened molecules as candidate biomarkers, and investigated serum IL-17A and complement components 3a (C3a) and C5a in order to evaluate whether these molecules show changes correlated to symptom scores. In this study, we found that the long-term SLIT reduced the serum levels of IL-17A and C3a and C5a. The levels of C3a in the patients significantly decreased from year 1 compared with those at the baseline, and their levels of IL-17A significantly decreased from year 2 compared with those at baseline. The levels of IL-17A, C3a, and C5a at year 4 of SLIT were significantly lower than not only those at baseline, but also those at year 1. A significant positive correlation was found between the symptom medication scores and the levels of IL-17A at year 4. The symptom medication scores in the group in which IL-17A levels decreased at year 4 were significantly lower than those in the group without such a decrease. The serum level of IL-17A might prove useful as a biological parameter to ascertain the effectiveness of SLIT for patients with SAR-JCP. It is necessary to produce new therapeutics for non-responders in whom serum IL-17A levels are still higher against long-term SLIT.

[Abilities needed by Japanese children to write kanji: Development of the ATLAN Kakitori subtest].

In the present study, we newly developed a kanji writing subtest of ATLAN (Adaptive Tests for Language Abilities), which is based on item response theory (Takahashi & Nakamura, 2009; Takahashi, Otomo, & Nakamura, 2012) and can be administered via the Internet. In Study 1, we evaluated two parameters, difficulty and discrimination, of 244 kanji characters based on the results of 1,306 children from 2nd to 9th grade. In Study 2, we analyzed kanji reading and writing subtests of 283 children from 3rd to 6th grade, including their error patterns and stroke order while writing kanji. The results of hierarchical regression analysis showed that more than 60% of the variance of kanji writing is explained by grade, kanji reading, and accuracy of forms and stroke order while writing kanji. The practical significance of the test is discussed.

Clinical expression in Pfeiffer syndrome type 2 and 3: surveillance in Japan.

Pfeiffer syndrome (PS) is a classic type of craniosynostosis syndrome. Severe cases usually require emergency care at birth. However, early diagnosis is often precluded by the rarity and consequent low awareness of this disease. This study aimed to clarify phenotypic expressions useful for the diagnosis of PS. We reviewed all cases of PS type 2 or 3 according to Cohen's classification that were reported between 1980 and 2011 in Japan. Clinical and genetic information were extracted from the patients' medical records. A total of 23 patients with PS type 2 or 3 were identified. All 23 patients presented with craniosynostosis, midface hypoplasia, proptosis, broad thumbs, and wide great toes. FGFR2 mutations were confirmed in all 8 patients in whom genetic analyses were performed. In addition to classic symptoms, elbow ankylosis and sacrococcygeal defects were present in 70% and 30% of the patients, respectively. During an average follow-up of 22 months, 22% of patients died before 1 year of age. Elbow ankylosis and sacrococcygeal defects were the phenotypic features recognizable at a glance. These defects strongly suggest the presence of PS in newborns with craniosynostosis.

Improving circulatory disturbance in transient abnormal myelopoiesis.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) is characterized by circulating blast cells in the blood. TAM usually resolves spontaneously, but several studies have associated this condition with early death, focusing on the development of effective treatments. We report the case of a neonate with DS who had TAM and novel GATA1 mutation. Although the patient eventually died of hepatic failure, exchange blood transfusion and low-dose cytarabine treatment dramatically improved pulmonary hypertension and acute renal failure refractory to conventional therapy. Such a blast-reducing approach might be useful for improving circulatory disturbances in neonates with DS and TAM.

Japanese children's understanding of notational systems.

This study examined Japanese children's understanding of two Japanese notational systems: hiragana and kanji. In three experiments, 126 3- to 6-year-olds were asked to name words written in hiragana or kanji as they appeared with different pictures. Consistent with Bialystok (Journal of Experimental Child Psychology, 2000, Vol. 76, pp. 173-189), 3- and 4-year-olds' identification of written words varied according to the picture with which they appeared, and older children named the words with different pictures more accurately. The 4-year-olds who could read words written in hiragana but could not read words written in kanji named both hiragana words and kanji words with different pictures more accurately than those who could not read hiragana and kanji words. The interrelationship between the symbol-sound relationships and the symbol-referent relationships of notational systems is discussed.

Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis is a global health problem that causes major illnesses and disability worldwide. Allergen-specific immunotherapy (SIT) is the only available treatment that can alter the natural course of allergic disease. However, the precise mechanism underlying allergen-SIT is not well understood. OBJECTIVE: The aim of the current study was to identify protein expression signatures reflective of allergen-SIT-more specifically, sublingual immunotherapy (SLIT). METHODS: Serum was taken twice from patients with seasonal allergic rhinitis caused by Japanese cedar: once before the pollen season and once during the season. A total of 25 patients was randomly categorized into a placebo-treated group and an active-treatment group. Their serum protein profiles were analyzed by 2-dimensional electrophoresis. RESULTS: Sixteen proteins were found to be differentially expressed during the pollen season. Among the differentially expressed proteins, the serum levels of complement C4A, apolipoprotein A-IV (apoA-IV), and transthyretin were significantly increased in SLIT-treated patients but not in placebo-treated patients. Among these proteins, the serum levels of apoA-IV correlated with the clinical symptom-medication scores (r = -0.635; P < .05) and with quality of life scores (r = -0.516; P < .05) in the case of SLIT-treated patients. The amount of histamine released from the basophils in vitro was greatly reduced after the addition of recombinant apoA-IV in the medium (P < .01). CONCLUSION: Our data will increase the understanding of the mechanism of SLIT and may provide novel insights into the treatment of allergic rhinitis.

Interleukin-19 downregulates interleukin-4-induced eotaxin production in human nasal fibroblasts.

BACKGROUND: Interleukin-19 (IL-19), a member of the IL-10 family, is characterized as the cytokine suppressing the release and function of several proinflammatory cytokines. For regulation of local reaction in allergic rhinitis (AR), IL-19 might play an especially important role. METHODS: We examined effects of IL-19 on IL-4-induced eotaxin production by human nasal fibroblasts. Early receptor-mediated events (expression of the suppressors of cytokine signaling (SOCS) and phosphorylation of signal transducer and activator of transcription 6 [STAT6]) by IL-19 was examined. Knockdown methods by RNAi were administered to investigate the involvement of those signal transductions. RESULTS: Pretreatment with IL-19 downregulates IL-4-induced eotaxin production, but not interferon-γ(IFN-γ)-induced RANTES. Pretreatment with IL-19 suppressed the IL-4-induced STAT6 phosphorylation. The IL-19 induced SOCS-1, but not SOCS-3 or SOCS-5. The SOCS-1 knockdown by RNAi diminished pretreatment with IL-19-induced down-regulation of eotaxin production. CONCLUSIONS: These results suggest that IL-19 down-regulates IL-4-induced eotaxin production via SOCS-1 in human nasal fibroblasts. In non-hematopoietic cells in AR, IL-19 might be an immunosuppressive factor.

Suppression of histone deacetylase 3 (HDAC3) enhances apoptosis induced by paclitaxel in human maxillary cancer cells in vitro and in vivo.

Inclusion of chemotherapeutic drugs in treatment of patients with newly diagnosed head and neck cancer has improved response rates and prolonged median survival. Nevertheless, most patients with advanced head and neck cancer are destined to relapse and to develop resistance to initially used drugs such as paclitaxel. Consequently, it has been more important in cancer therapy to determine the molecular mechanisms that are related to cell-killing effects of anti-cancer agents or cancer resistance against them. Consequently, we examined whether abrogation of histone deacetylase 3 (HDAC3) expression by anti-sense oligonucleotides (ASOs) potentiates the efficacy of paclitaxel in human maxillary cancer IMC-3 cells. Here, we showed that paclitaxel-induced apoptosis was enhanced significantly by addition of ASOs for HDAC3 in cultured cells. Furthermore, paclitaxel-induced apoptosis in IMC-3 tumors transplanted in nude mice was enhanced significantly by administration of ASOs for HDAC3, thereby suppressing tumor growth. We provide new evidence that HDAC3 is a novel molecular target whose inactivation can potentiate the efficacy of anti-cancer drugs disrupting microtubules such as paclitaxel.

Poly(I:C) induces BLyS-expression of airway fibroblasts through phosphatidylinositol 3-kinase.

B lymphocyte stimulator (BLyS), B cell activating factor (BAFF), a member of the tumor necrosis factor ligand superfamily has potent co-stimulatory activity on B cells, and BLyS-production in the airway mucosa is of potential importance as it triggers innate and adaptive immune responses. To investigate whether airway fibroblast could express BLyS, we examined BLyS-expression in human nasal airway fibroblasts and compared to its expression in tonsillar and skin fibroblasts as well as the effect of the Toll-like receptor (TLR) ligands on that in human nasal airway fibroblasts. The expression of BLyS by nasal fibroblasts in the presence of polyinocinic-polycytidykic acid (poly(I:C)) was markedly induced, to a level of more than 100 times higher than that observed in the absence of poly(I:C). In order to demonstrate the intracellular pathways involved in poly(I:C)-induced BLyS-expression, we used specific inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), spleen tyrosine kinase (Syk), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and extracellular-signal related kinase (ERK)-signaling in these events. Pre-incubation with the PI3-kinase inhibitor LY294002 or Wortmanin reversed the poly(I:C)-induced production and expression of BLyS. Syk kinase inhibitor Piceatannol partially reduced its production and expression. Thus, we were able to show that PI3-kinase signaling is directly involved in poly(I:C)-induced BLyS-expression in nasal airway fibroblasts. These results indicate that human nasal airway fibroblasts strongly induce BLyS-expression and production by poly(I:C) through PI3-K signaling during airway immune responses.

Age-related clinical characteristics of isolated congenital unilateral absence of a pulmonary artery.

Unilateral absence of a pulmonary artery (UAPA) is a rare anomaly. Although UAPA has been reported previously, its age-related pathogenesis and symptoms remain unclear. This retrospective cohort study included cases of UAPA reported in Japan at medical meetings or in the literature from 1990 through 2009. Patients with other congenital cardiac defects were excluded from the study. Clinical status was assessed according to age, and the clinical course of patients with isolated UAPA was compared with that of patients who had UAPA with a patent ductus arteriosus (PDA). Of the 92 patients with UAPA identified, 78 had isolated UAPA (14 with PDA). Hemoptysis and collateral arteries were observed in 0 and 13% of patients with isolated UAPA who were younger than 1 year, as compared with 24 and 50% of those 20 years of age or older, respectively. Pulmonary hypertension was present in 5% of the patients aged 1 to 19 years. Among patients 20 years or older, however, 32% had pulmonary hypertension, and 8% died. Compared with isolated UAPA, UAPA with PDA was associated with an earlier diagnosis (median age, 20 vs. 0 years; p = 0.002), a higher prevalence of pulmonary hypertension (22% vs. 86%; p < 0.0001), and a higher mortality rate (4% vs. 21%; p = 0.046). Collateral artery formation and pulmonary hypertension progress with age in patients with UAPA. Early diagnosis and revascularization may prevent the age-related progression of UAPA.

Vision-assisted micromanipulation using closed-loop actuation of multiple microrobots.

Accurate control and precise positioning of opto-thermocapillary flow-addressed bubble microrobots are necessary for micromanipulation. In addition, micromanipulation using the simultaneous actuation of multiple microrobots requires a robust control system to enable independent motion. This paper demonstrates a hybrid closed-loop vision-assisted control system capable of actuating multiple microrobots simultaneously and positioning them at precise locations relative to micro-objects under manipulation. A vision-assisted grasp-planning application was developed and used to calculate the necessary trajectories of the microrobots to form cages around micro-objects. The location of the microrobots and the micro-objects was detected at the caging locations using a particle-tracking application that used image feedback for precise positioning. The closed-loop image feedback information enabled the position update of the microrobots, allowing them to precisely follow the trajectory and caging locations calculated by the grasp-planning application. Four microrobots were assigned to cage a star-shaped micro-object using the closed-loop control system. Once caged, the micro-object was transported to a location within the workspace and uncaged, demonstrating the micromanipulation task. This microrobotic system is well suited for the micromanipulation of single cells.

Inhibition of histone deacetylase 3 stimulates apoptosis induced by heat shock under acidic conditions in human maxillary cancer.

To elucidate the molecular mechanisms for the enhancement of heat-induced apoptosis on exposure to acidic conditions, human maxillary carcinoma IMC-3 cells were heat-shocked at 44 degrees C for 30 min at either pH 7.4 or 6.7. Analyses with cDNA arrays, the reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were performed. We found that histone deacetylase 3 (HDAC3) was specifically induced after hyperthermia at 44 degrees C for 30 min at pH 6.7. Although the cytotoxicity of heating at 44 degrees C for 30 min was enhanced by decreasing the pH from 7.4 to 6.7, it was enhanced even more by antisense RNA oligonucleotides for HDAC3. The induction of G2/M arrest after heating occurred earlier at pH 6.7 than at pH 7.4. The inhibition of HDAC3 by the antisense RNA oligonucleotides suppressed partially the induction of G2/M arrest, resulting in an enhancement of the apoptosis caused by the heating under acidic conditions. Antisense RNA oligonucleotides for HDAC3 enhanced apoptosis 48 h after hyperthermia at 43 degrees C for 30 min in vivo. Analyses of p65 activity suggested that NF-kappaB is involved in this enhancement of hyperthermia. HDAC3 may be a novel target enhancing hyperthermia and combined treatment with hyperthermia and HDAC inhibitors is a possible modality for cancer therapy.

Oral and oropharyngeal squamous cell carcinomas expressing CCR7 have poor prognoses.

OBJECTIVE AND METHODS: Tumor cell migration and metastasis have many similarities with leukocyte trafficking regulated by chemokines and their receptors. In this study, we investigated the expression of CC chemokine receptor 7 (CCR7) in oral and oropharyngeal squamous cell carcinomas (SCCs) using an immunohistochemical approach. RESULTS: Among 90 cases of oral and oropharyngeal SCCs, 54 cases (60%) were positive for CCR7. The CCR7-positive group had a significantly lower incidence of being disease-free and an overall lower survival rate than the CCR7-negative group (p<0.01 and p<0.01, respectively). Among the 35 patients who died of cancer, 28 patients (80%) were positive for CCR7. The expression of CCR7 was significantly associated with five clinical factors. SCCs expressing CCR7 tend to have large, lymph node metastases, progressive stages, local recurrences and cancer death. The CCR7 expression of metastatic SCCs in draining lymph nodes was detected, and the staining score of CCR7 between primary SCCs and metastatic SCCs were significantly correlated (p<0.01). CONCLUSIONS: The investigation of CCR7 expression in oral and oropharyngeal SCCs may be useful to predict patients prognoses.

[A case of the lateral ventricle lesion mimicking arachnoid cyst treated by neuroendoscopic surgery].

A 12-year-old female suffered from intermittent headache with nausea. Neuroradiologic studies demonstrated a cystic lesion in the right trigone with content like cerebrospinal fluid. The right inferior horn was isolated and increased in size. Eodoscopic fenestration was attempted using a flexible fiberscope via the inferior horn. Postoperative magnetic resonance image revealed shrinkage of the cyst and reduced size of the right inferior horn. Intermittent headache dissapeared. Neuroendoscopic treatment is a less invasive and effective therapy for intraventricular arachnoid cyst as well that in the other intracranial lesion.

Interdigitated craniotomy: a simple technique to fix a bone flap with only a single plate.

In pterional craniotomy, fixation plates cause artifacts on postoperative radiological images; furthermore, they often disfigure the scalp in hairless areas. The authors describe a simple technique to fix a cranial bone flap with only a single plate underneath the temporalis muscle in an area with hair, rather than using a plate in a hairless area. The key to this technique is to cut the anterior site of the bone flap at alternate angles on the cut surface. Interdigitation between the bone flap and skull enables single-plate fixation in the area with hair, which reduces artifacts on postoperative radiological images and provides excellent postoperative cosmetic results.