Refeeding Hypophosphatemia in Anorexia Nervosa

Objective: Refeeding in patients with anorexia nervosa (AN) is associated with a risk of refeeding syndrome (RS), which is a disruption in metabolism with a variety of features including hypophosphatemia. We evaluated the risk factors for refeeding hypophosphatemia (RH) during nutritional replenishment in Japanese patients with AN. Methods: We retrospectively examined clinical data for 99 female inpatients (mean age 30.9 ± 10.7 years, range: 9 to 56 years). Results: RH (phosphate <2.3 mg/dL) occurred within 4.8 ± 3.7 days of hospital admission and was still observed at 28 days after admission in 21 of the 99 cases (21.2%). Oral or intravenous phosphate was given to some patients to treat or prevent RH. Patients with RH had a significantly lower body mass index, were older, and had higher blood urea nitrogen than those without RH. Severe complications associated with RH were recorded in only one patient who showed convulsions and disturbed consciousness at day 3 when her serum phosphate level was 1.6 mg/dL. Conclusion: The significant risk factors for RH that we identified were lower BMI, older age, and higher blood urea nitrogen at admission. No significant difference in total energy intake was seen between the RH and no RH groups, suggesting that RH may not be entirely correlated with energy intake. Precisely predicting and preventing RH is difficult, even in patients with AN who are given phosphate for prophylaxis. Thus, serum phosphate levels should be monitored for at least 5-10 days after admission

Language development in Japanese children who receive cochlear implant and/or hearing aid

Objectives: This study aimed to investigate a wide variety of factors that influence auditory, speech, and language development following pediatric cochlear implantation (CI). Study design: Prospective collection of language tested data in profound hearing-impaired children. Hypothesis: Pediatric CI can potentially be effective to development of practical communication skills and early implantation is more effective. Methods: We proposed a set of language tests (assessment package of the language development for Japanese hearing-impaired children; ALADJIN) consisting of communication skills testing (test for question-answer interaction development; TQAID), comprehensive (Peabody Picture Vocabulary Test-Revised; PVT-R and Standardized Comprehension Test for Abstract Words; SCTAW) and productive vocabulary (Word Fluency Test; WFT), and comprehensive and productive syntax (Syntactic processing Test for Aphasia; STA). Of 638 hearing-impaired children recruited for this study, 282 (44.2%) with >70 dB hearing impairment had undergone CI. After excluding children with low birth weight (11 points on the Pervasive Developmental Disorder ASJ Rating Scale for the test of autistic tendency, and those <2 SD on Raven's Colored Progressive Matrices for the test of non-verbal intelligence, 190 children were subjected to this set of language tests. Results: Sixty children (31.6%) were unilateral CI-only users, 128 (67.4%) were CI-hearing aid (HA) users, and 2 (1.1%) were bilateral CI users. Hearing loss level of CI users was significantly (p < 0.01) worse than that of HA-only users. However, the threshold level, maximum speech discrimination score, and speech intelligibility rating in CI users were significantly (p < 0.01) better than those in HA-only users. The scores for PVT-R (p < 0.01), SCTAW, and WET in CI users were better than those in HA-only users. STA and TQAID scores in CI-HA users were significantly (p < 0.05) better than those in unilateral CI-only users. The high correlation (r = 0.52) has been found between the age of CI and maximum speech discrimination score. The scores of speech and language tests in the implanted children before 24 months of age have been better than those in the implanted children after 24 months of age. Conclusions: We could indicate that CI was effective for language development in Japanese hearing-impaired children and early CI was more effective for productive vocabulary and syntax.ArticleINTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY. 76(3):433-438 (2012)journal articl

双極性障害におけるグルタミン酸神経伝達異常に関するMRS研究

Background: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gln) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system. Methods: Sixty-two subjects (31 patients with BD and 31 healthy controls [HC]) underwent 3T proton MRS (1H-MRS) of the anterior cingulate cortex (ACC) and left basal ganglia (ltBG) using a stimulated echo acquisition mode (STEAM) sequence. Results: After verifying the data quality, 20 patients with BD and 23 age- and gender-matched HCs were compared using repeated-measures analysis of covariance (ANCOVA). Compared to the HC group, the BD group showed increased levels of Gln, creatine (Cr), N-acetyl aspartate (NAA), choline (Cho), and an increased ratio of Gln to Glu in the ACC, and increased Gln and Cho in the ltBG. These findings remained after the participants with BD were limited to only euthymic patients. After removing the influence of lithium (Li) and sodium valproate (VPA), we observed activated glutamatergic neurotransmission in the ACC but not in the ltBG. Limitations: The present findings are cross-sectional and metabolites were measured in only two regions. Conclusions: Our results support a wide range of metabolite changes in patients with BD involved in glutamatergic neurotransmission, membrane turnover, and neuronal integrity. Moreover, the elevation of Gln/Glu ratio suggested that hyperactivity of glutamatergic neurotransmission in the ACC is a disease marker for BD

Robust and highly efficient hiPSC generation from patient non-mobilized peripheral blood-derived CD34+ cells using the auto-erasable Sendai virus vector

Background: Disease modeling with patient-derived induced pluripotent stem cells (iPSCs) is a powerful tool forelucidating the mechanisms underlying disease pathogenesis and developing safe and effective treatments. Patientperipheral blood (PB) cells are used for iPSC generation in many cases since they can be collected with minimuminvasiveness. To derive iPSCs that lack immunoreceptor gene rearrangements, hematopoietic stem and progenitorcells (HSPCs) are often targeted as the reprogramming source. However, the current protocols generally requireHSPC mobilization and/or ex vivo expansion owing to their sparsity at the steady state and low reprogrammingefficiencies, making the overall procedure costly, laborious, and time-consuming.Methods: We have established a highly efficient method for generating iPSCs from non-mobilized PB-derivedCD34+ HSPCs. The source PB mononuclear cells were obtained from 1 healthy donor and 15 patients and werekept frozen until the scheduled iPSC generation. CD34+ HSPC enrichment was done using immunomagnetic beads,with no ex vivo expansion culture. To reprogram the CD34+-rich cells to pluripotency, the Sendai virus vectorSeVdp-302L was used to transfer four transcription factors: KLF4, OCT4, SOX2, and c-MYC. In this iPSC generationseries, the reprogramming efficiencies, success rates of iPSC line establishment, and progression time wererecorded. After generating the iPSC frozen stocks, the cell recovery and their residual transgenes, karyotypes, T cellreceptor gene rearrangement, pluripotency markers, and differentiation capability were examined.Results：We succeeded in establishing 223 iPSC lines with high reprogramming efficiencies from 15 patients with 8 different disease types. Our method allowed the rapid appearance of primary colonies (~ 8 days), all of which were expandable under feeder-free conditions, enabling robust establishment steps with less workload. After thawing, the established iPSC lines were verified to be pluripotency marker-positive and of non-T cell origin. A majority of the iPSC lines were confirmed to be transgene-free, with normal karyotypes. Their trilineage differentiation capability was also verified in a defined in vitro assay.Conclusion：This robust and highly efficient method enables the rapid and cost-effective establishment of transgene-free iPSC lines from a small volume of PB, thus facilitating the biobanking of patient-derived iPSCs and their use for the modeling of various diseases

Tissue-Restricted Expression of Nrf2 and Its Target Genes in Zebrafish with Gene-Specific Variations in the Induction Profiles

The Keap1-Nrf2 system serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than one hundred cytoprotective proteins, including antioxidants and phase 2 detoxifying enzymes. Since induction profiles of Nrf2 target genes have been studied exclusively in cultured cells, and not in animal models, their tissue-specificity has not been well characterized. In this paper, we examined and compared the tissue-specific expression of several Nrf2 target genes in zebrafish larvae by whole-mount in situ hybridization (WISH). Seven zebrafish genes (gstp1, mgst3b, prdx1, frrs1c, fthl, gclc and hmox1a) suitable for WISH analysis were selected from candidates for Nrf2 targets identified by microarray analysis. Tissue-restricted induction was observed in the nose, gill, and/or liver for all seven genes in response to Nrf2-activating compounds, diethylmaleate (DEM) and sulforaphane. The Nrf2 gene itself was dominantly expressed in these three tissues, implying that tissue-restricted induction of Nrf2 target genes is defined by tissue-specific expression of Nrf2. Interestingly, the induction of frrs1c and gclc in liver and nose, respectively, was quite low and that of hmox1a was restricted in the liver. These results indicate the existence of gene-specific variations in the tissue specificity, which can be controlled by factors other than Nrf2

Fluctuating single sp2 carbon clusters at single hotspots of silver nanoparticle dimers investigated by surface-enhanced resonance Raman scattering

We evaluate spectral changes in surface enhanced resonance Raman scattering (SERRS) of near-single dye molecules in hotspots of single Ag nanoparticle (NP) dimers. During the laser excitation, surface enhance florescence (SEF) of dye disappeared and the number of SERRS lines decreased until finally ca. two lines remained around 1600 and 1350 cm−1, those are evidence of G and D lines of single sp2 carbon clusters. Analysis of the G and D line intensity ratios reveals the temporal fluctuation in the crystallite size of the clusters within several angstroms; whereas, broadening and splitting in the lines enable us for identifying directly the dynamics of various defects in the clusters. This analysis reveals that the detailed fluctuations of single sp2 carbon clusters, which would be impossible to gain with other microscopic methods

Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Besides the exogenous stress response, Nrf2 has been found to regulate numerous cellular functions, including protein turnover and glucose metabolism; however, the evolutionary origins of these functions remain unknown. In the present study, we searched for novel target genes associated with the zebrafish Nrf2 to answer this question. A microarray analysis of zebrafish embryos that overexpressed Nrf2 revealed that 115 candidate genes were targets of Nrf2, including genes encoding proteasome subunits and enzymes involved in glucose metabolism. A real-time quantitative PCR suggested that the expression of 3 proteasome subunits (psma3, psma5, and psmb7) and 2 enzymes involved in glucose metabolism (pgd and fbp1a) were regulated by zebrafish Nrf2. We thus next examined the upregulation of these genes by an Nrf2 activator, diethyl maleate, using Nrf2 mutant zebrafish larvae. The results of real-time quantitative PCR and whole-mount in situ hybridization showed that all of these 5 genes were upregulated by diethyl maleate treatment in an Nrf2-dependent manner, especially in the liver. These findings implied that the Nrf2-mediated regulation of the proteasome subunits and glucose metabolism is evolutionarily conserved among vertebrates

Pyrophosphate Chemistry toward Safe Rechargeable Batteries

We demonstrate that pyrophosphate anion can result in metal pyrophosphate cathode materials with high thermal stabilities. High temperature behaviors for the delithiated states of Li₂FeP₂O₇ and Li₂MnP₂O₇ in the <i>P</i>2₁/<i>c</i> symmetry are studied. Above 540 °C, the singly delithiated structure LiFeP₂O₇ undergoes an irreversible phase transformation to the ground state polymorph with a symmetry of <i>P</i>2₁. Intermediate delithiated compounds Li_2‑<i>x</i>FeP₂O₇ (0 < <i>x</i> < 1) convert to a mixture of LiFeP₂O₇ in the <i>P</i>2₁ symmetry and Li₂FeP₂O₇ in the <i>P</i>2₁/<i>c</i> symmetry. No decomposition is observed for both the singly and partially delithiated compounds until 600 °C showing the high thermal stabilities of the compounds. Analysis of phase stabilities reveals that LiFeP₂O₇ (<i>P</i>2₁/<i>c</i>) is intrinsically more stable than FePO₄ (olivine) against reduction (high temperature). Similar high thermal stability is also observed for Li_1.4MnP₂O₇. It decomposes to Li₂MnP₂O₇, Mn₂P₂O₇, LiPO₃, and O₂ at 450 °C, much higher than the olivine counterpart MnPO₄. The high stability of these metal pyrophosphates is rationalized by the stability of the P₂O₇^4‑ anion

Femtosecond pulsed laser as a microscalpel for microdissection and isolation of specific sections from biological samples

The femtosecond laser is a candidate tool for dissecting and obtaining specific tissues or cells from biological samples. In this paper, we report on the dissection of flammable (heat-sensitive) plant tissues (Eucommia ulmoides stem) and that of a transparent zebrafish embryo placed in water. During laser dissection in the plant tissues, we observed that a low repetition rate of the irradiations is crucial for reducing the risk of thermal damage. During laser dissection of the zebrafish embryo, the laser-induced bubble formation at the tissue surface disturbed the laser-induced dissection. We concluded that the "interior laser dissection method", in which the dissection is performed by moving the laser spot inside a biological sample, is an efficient way to dissect a sample that is placed in water. In view of our findings, the advantages of fs laser dissection are discussed on the basis of the physical characteristics of fs laser machining