Association of Familial Fanconi Syndrome with a Novel GATM Variant.

Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome.

Photocatalytic formation of a gas permeable layer selectively deposited on supported metal nanoparticles for sintering-resistant thermal catalysis.

Nanoparticle aggregation of supported metal catalysts at high temperatures is a serious problem that causes a drop in catalytic performance. This study investigates the protection of metal nanoparticles from sintering by selectively forming nanoscale SiO2 shells on Pd supported on TiO2 by ultraviolet (UV) light irradiation. The proton-coupled reduction reaction increases the local pH around Pd nanoparticles, resulting in hydrolysis of tetraethoxyorthosilicate (TEOS) in only the vicinity of the metal. An apparent quantum efficiency of only 0.6% is obtained for the Pd/TiO2 catalyst in H2 evolution from ethanol-containing water under 370 nm excitation light. Therefore, the pH of raw slurry solution should be precisely controlled to that slightly below the threshold value for the TEOS hydrolysis reaction before the photodeposition. Transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX) clearly show that the particle size of the Pd nanoparticles (∼40 nm) with the SiO2 shell (∼20 nm) was almost unchanged by the high-temperature treatment at 900 °C in air, suggesting that the SiO2 shell prevented thermal aggregation of Pd nanoparticles. The Pd/TiO2 without SiO2 shell decoration exhibited a drop in the number of active sites, which was likely due to aggregation of the Pd catalysts. However, the number of active sites on the Pd@SiO2/TiO2 catalyst was maintained even after the catalyst was calcined at 900 °C. Consequently, the Pd@SiO2/TiO2 catalyst maintained its catalytic performance for simulated exhaust gas purification even after treatment at 900 °C. This study presents a methodology to produce sintering-tolerant supported metal nanoparticles using the photocatalytic gas permeable layer fabrication method.

Real-world efficacy and safety of glecaprevir/pibrentasvir in Japanese adolescents with chronic hepatitis C: a prospective multicenter study.

BACKGROUND: Part 1 of the DORA study, a 2019 international clinical trial of glecaprevir and pibrentasvir (G/P) treatment in adolescents with chronic hepatitis C virus (HCV) infection, demonstrated high efficacy and safety. However, few reports have considered real-world experience with G/P treatment in adolescents with chronic HCV. The present prospective multicenter study assessed real-world efficacy and safety of G/P treatment in Japanese adolescents with chronic HCV. METHODS: Subjects between 12 and 17 years old who were treatment-naïve or previously managed with interferon-based regimens were prospectively enrolled and treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virologic response at 12 weeks after treatment completion (SVR12). Adverse effects and laboratory abnormalities were assessed. RESULTS: Twenty-five Japanese patients (15 female) were enrolled from 13 pediatric centers in Japan. Median age was 13 years (range 12-17). Numbers of patients with genotypes 1b, 2a, 2b, and 2b/1b were 6, 12, 6, and 1, respectively. Twenty-two were treatment-naïve, while three had experienced interferon-based treatments. All patients completed G/P treatment (24 for 8 weeks and 1 for 12). Twenty-four achieved SVR12 (96%). Most adverse events were mild. None were serious. G/P significantly decreased serum alanine aminotransferase, γ-glutamyltransferase, and Wisteria floribunda agglutinin-positive Mac-2-binding protein concentrations. No negative effects on growth or maturation were apparent at 12 weeks. CONCLUSIONS: Under real-world conditions, G/P treatment of Japanese adolescents with chronic HCV was highly efficacious and well tolerated.

Positive Psychology Broadens Readers' Attentional Scope During L2 Reading: Evidence From Eye Movements.

While positive psychology has drawn increasing interests among researchers in the second language (L2) acquisition literature recently, little is known with respect to the relationship between positive psychology and mental processes during L2 reading. To bridge the gap, the present study investigated whether and how positive psychology (self-efficacy) influences word reading strategies during L2 sentence reading. Based on previous studies, eye-movement patterns with first-fixation locations closer to the beginning of a word can be characterized as an attempt to process the word with a local strategy, whereas first-fixation locations farther away from the beginning and closer to the center of a word can be considered as an attempt to use a global strategy. Eye movements of a group of Japanese learners of English (N = 59) were monitored, and L2 reading self-efficacy was used to assess the participants' positive belief toward their L2 reading skills. Based on Fredrickson's (1998) broaden-and-build theory, we predicted an effect of L2 reading self-efficacy on participants' first-fixation locations. Results from mixed-effects regression showed that while reading strategies depended in part on other factors such as L2 reading proficiency and word properties, L2 self-efficacy influenced reading strategy. The present data suggest that while more self-efficacious L2 readers prefer a more efficient global strategy, attempting to read the word as a whole word, less self-efficacious L2 readers tend to employ a local strategy, focusing more on sublexical information. These findings lend support to the broaden-and-build theory in the context of L2 processing. The present study has implications for how positive psychology works along with L2 proficiency in the development of strategic selection during reading.

Perovskite lattice oxygen contributes to low-temperature catalysis for exhaust gas cleaning.

A Pd catalyst supported on Ba-substituted LaAlO3 perovskite (Pd/La0.9Ba0.1AlO3-δ ) was investigated for NO reduction at low temperature by propylene, which revealed that Pd/La0.9Ba0.1AlO3-δ has remarkably higher activity than other Pd catalysts at low temperatures (≤573 K) for NO reduction by propylene. To elucidate the surface reaction pathway, transient response tests were conducted using 18O2. Also, X-ray photoelectron spectroscopy (XPS) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) measurements were conducted. Comparison with a Ba-impregnated catalyst (Pd/Ba/LaAlO3) demonstrated that Pd/La0.9Ba0.1AlO3-δ shows higher activity for the formation of oxygenated species (C x H y O z ) as an intermediate for NO reduction because the surface lattice oxygen has improved mobility via Ba2+ substitution in LaAlO3. Therefore, Pd/La0.9Ba0.1AlO3-δ have high activity for NO reduction, even at low temperatures in a humid condition.

Arrhythmia risk and ß-blocker therapy in pregnant women with long QT syndrome.

BACKGROUND: Pregnancy is one of the biggest concerns for women with long QT syndrome (LQTS). OBJECTIVES: This study investigated pregnancy-related arrhythmic risk and the efficacy and safety of ß-blocker therapy for lethal ventricular arrhythmias in pregnant women with LQTS (LQT-P) and their babies. METHODS: 136 pregnancies in 76 LQT-P (29±5 years old; 22 LQT1, 36 LQT2, one LQT3, and 17 genotype-unknown) were enrolled. We retrospectively analysed their clinical and electrophysiological characteristics and pregnancy outcomes in the presence (BB group: n=42) or absence of ß-blocker therapy (non-BB group: n=94). RESULTS: All of the BB group had been diagnosed with LQTS with previous events, whereas 65% of the non-BB group had not been diagnosed at pregnancy. Pregnancy increased heart rate in the non-BB group; however, no significant difference was observed in QT and Tpeak-Tend intervals between the two groups. In the BB group, only two events occurred at postpartum, whereas 12 events occurred in the non-BB group during pregnancy (n=6) or postpartum period (n=6). The frequency of spontaneous abortion did not differ between the two groups. Fetal growth rate and proportion of infants with congenital malformation were similar between the two groups, but premature delivery and low birthweight infants were more common in those taking BB (OR 4.79, 95% CI 1.51 to 15.21 and OR 3.25, 95% CI 1.17 to 9.09, respectively). CONCLUSIONS: Early diagnosis and ß-blocker therapy for high-risk patients with LQTS are important for prevention of cardiac events during pregnancy and the postpartum period, and ß-blocker therapy may be tolerated for babies in LQT-P cases.

SOX3 Overdosage Permits Normal Sex Development in Females with Random X Inactivation.

Submicroscopic duplications involving SOX3 and/or its flanking regions have been identified in 46,XX individuals both with and without disorders of sex development, raising the question whether SOX3 overdosage is sufficient to induce testicular development in genetically female individuals. Here, we report a mother-daughter pair with female phenotypes and random X inactivation. The individuals carry complex X chromosomal rearrangements leading to a copy number gain of genomic regions involving SOX3 and its upstream region. The amplified DNA fragments were detected at Xq27. These results provide evidence that SOX3 overdosage permits normal sex development in 46,XX individuals with random X inactivation.

Elevated serum levels of neutrophil elastase in patients with influenza virus-associated encephalopathy.

We examined serum levels of various cytokines, chemokines, growth factors, and adhesion molecules in patients with uncomplicated influenza (n=20) and influenza virus-associated encephalopathy (IE) (n=18) to understand the underlying mechanism of IE. We found that IL-1ß, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, GM-CSF, TNF-α, TIMP-1, MMP-9, sE-selectin, and neutrophil elastase were elevated significantly in sera from patients with uncomplicated influenza and those with IE, compared with normal controls (n=20). Of note, neutrophil elastase, sE-selectin, IL-8, and IL-13 were elevated significantly in IE as compared with uncomplicated influenza. In the present study, for the first time, we found that serum levels of neutrophil elastase were increased in patients with IE compared with uncomplicated influenza, which suggested that cerebral endothelial damage in the development of IE was mediated by neutrophil elastase. The present study implied that anti-elastase agents are possibly an effective therapeutic protocol for IE, but this needs further elucidation.

Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance.

Two distinct human light subunits of the heteromeric amino acid transporter, y+LAT-1 coded by SLC7A7 and y+LAT-2 coded by SLC7A6, are both known to induce transport system y+L activity. SLC7A7 has already been identified as the gene responsible for lysinuric protein intolerance (LPI). We successfully identified five novel SLC7A7 variants (S238F, S489P, 1630delC, 1673delG, and IVS3-IVS5del9.7kb) in Japanese patients with LPI by PCR amplification and direct DNA sequencing. In addition, we performed a semi-quantitative expression analysis of SLC7A7 and SLC7A6 in human tissue. In normal tissue, the gene-expression ratio of SLC7A6 to SLC7A7 was high in the brain, muscle, and cultured skin fibroblasts; low in the kidneys and small intestine; and at an intermediate level in peripheral blood leukocytes, the lungs, and cultured lymphoblasts. The gene-expression ratio of SLC7A6 to SLC7A7 in cultured lymphoblasts was significantly different between normal subjects and LPI patients with R410X and/or S238F, where the relative amount of SLC7A7 mRNA was significantly lower and the relative amount of SLC7A6 mRNA was statistically higher in affected lymphoblasts than in normal cells. Expression of SLC7A7 and SLC7A6 may thus be interrelated in cultured lymphoblasts.