Effects of the abacus-based mental calculation training application "SoroTouch" on cognitive functions: A randomized controlled trial.

This study investigated the effect of a home-based computerized cognitive training program that utilizes a digital application for training abacus-based mental calculations, "SoroTouch," on the cognitive functions of healthy middle-aged and older people using a randomized controlled trial. The participants were 20 adults (aged 42-79 years) who were involved in community-based activities for dementia prevention held by a certain organization. The participants were assigned randomly to the intervention (SoroTouch) group or control group. The SoroTouch group received home-based cognitive training with SoroTouch, being asked to use the software every day for 6 months, while the control group did not receive any intervention. To investigate the effect of SoroTouch, CogEvo, a cognitive functions test battery utilizing a tablet device, was administered to all participants once per month during the 6-month intervention period. In addition, before and after the intervention, all participants were asked to take the CogEvo and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The analyses showed that the SoroTouch group did not improve total scores of the CogEvo and MoCA-J, but large group differences were observed in the two tasks of the CogEvo as follows: 'Follow the order' (modified Trail Making Test) at 2 months after the beginning of the intervention (group differences; 39.4, 95% confidence interval; 7.6-71.2) and 'Route 99' at 6 months (group differences; 39.6, 95% confidence interval; 4.9-74.4). These results provide evidence that a home-based computerized cognitive training program SoroTouch has the potential to improve working memory, attention and planning in healthy middle-aged and older adults.

Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations.

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 ∼ 50-100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 ∼ 40-60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation.

Risk factors for postoperative nausea and vomiting in patients of orthognathic surgery according to the initial onset time: a cross-sectional study.

Background: A high incidence (40-73%) of postoperative nausea and vomiting (PONV) has been reported following orthognathic surgery, and various risk factors have been associated with it. Identifying PONV risk factors based on initial onset time will help establish preventive measures. This study aimed to identify factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. Methods: This study included 590 patients who underwent orthognathic surgery. Multivariate logistic regression analysis was performed to identify the risk factors that are significantly related to PONV. The objective variables were classified into three categories: no PONV, early PONV (initial onset time: 0-2 h after anesthesia), and late PONV (initial onset time: 2-24 h after anesthesia). The explanatory variables included relevant risk factors for PONV, as considered in previous studies. Results: Total intravenous anesthesia with propofol was a significant depressant factor for early PONV (adjusted odds ratio [aOR] = 0.340, 95% confidence interval [CI] = 0.209-0.555) and late PONV (aOR = 0.535, 95% CI = 0.352-0.814). The administration of a combination of intraoperative antiemetics (vs. no administration) significantly reduced the risk of early PONV (aOR = 0.464, 95% CI = 0.230-0.961). Female sex and young age were significant risk factors for late PONV (aOR = 1.492, 95% CI = 1.170-1.925 and unit aOR = 1.033, 95% CI = 1.010-1.057, respectively). Conclusion: We identified factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. Total intravenous anesthesia with propofol significantly reduced the risk of PONV not only in the early period (0-2 h after anesthesia) but also in the late period (2-24 h after anesthesia).

Limitation of developmental test to measure functional independence of children: Relationship between the Japanese version of WeeFIM II® and KSPD.

PURPOSE: The purpose of the study was to explore whether a developmental test provides enough information to estimate a child's functional independence. The strength of the relationship between developmental level and functional independence of different skills was investigated. METHODS: The participants were 397 children (age 0-7 years) who were referred to NCCHD for suspected developmental delay. The participants' developmental level was measured with the Kyoto Scale of Psychological Development (KSPD) and their functional independence was assessed through a Japanese version of the WeeFIM II®. To calculate the strengths of the relationship between developmental age (DA) in different domains of the KSPD and WeeFIM II item scores, partial correlation analyses were conducted, controlling for chronological age. RESULTS: Partial correlation coefficients between the score of each of the 18 WeeFIM II items and each of the three KSPD domain DAs (controlling chronological age) fell in the ranges of r = 0.169-0.581 (Posture-Motor; P-M), r = 0.377-0.627 (Cognitive-Adaptive; C-A), and r = 0.332-0.655 (Language-Social; L-S). When the participants were divided into three age groups, the correlations ranged from -0.095 to 0.552 for the youngest group (mean age = 14.21 months), from 0.283 to 0.653 for the middle group (mean age = 32.98 months), and from 0.345-0.692 for the oldest group (mean age = 57.48 months), depending on the combinations of the WeeFIM II items/developmental domains of the KSPD. The results indicated that for most of the daily living skills, its functional independence was only partially explained by the scores of a developmental test, once chronological age was controlled. CONCLUSION: This study showed the limitation of a developmental test as a tool to measure the functional independence of children and the necessity of using an independent tool, such as WeeFIM II, to evaluate the level of required support for each daily living skill.

Developmental outcomes in Japanese preschool-age children conceived through assisted reproductive technology.

AIM: This study aimed to investigate the developmental outcomes of Japanese babies conceived through assisted reproductive technology (ART), born at ages 48 and 60 months. METHODS: Data were collected from 725 children in a hospital-based cohort study conducted in Japan. The children's level of development was assessed using the Kinder Infant Development Scale, a parent-rated questionnaire that consists of nine developmental domains. We compared the development between children conceived through ART (N = 189) and those conceived naturally (N = 536) by conducting analyses of covariance. For the analyses, we controlled for the effects of maternal age, family income, parental education, and multiple births. RESULTS: At 48 months, no significant difference was found between children conceived through ART and those conceived naturally, except for the development of receptive language (F(1, 718) = 4.869, p = 0.028)), which was found only for boys. The mean developmental age of receptive language was 60.1 for the children conceived through ART and 57.5 for those conceived naturally. At 60 months, no significant difference was found between children conceived through ART and those conceived naturally, in all domains. CONCLUSION: At ages 48 and 60 months, no significant difference was found between the children conceived through ART and those conceived naturally in nine developmental domains, except for boys' receptive language at 48 months.

Characterization of Aurintricarboxylic Acid (ATA) Interactions with Plasma Transporter Protein and SARS-CoV-2 Viral Targets: Correlation of Functional Activity and Binding Energetics.

In an effort to identify functional-energetic correlations leading to the development of efficient anti-SARS-CoV-2 therapeutic agents, we have designed synthetic analogs of aurintricarboxylic acid (ATA), a heterogeneous polymeric mixture of structurally related linear homologs known to exhibit a host of biological properties, including antiviral activity. These derivatives are evaluated for their ability to interact with a plasma transporter protein (human serum albumin), eukaryotic (yeast) ribosomes, and a SARS-CoV-2 target, the RNA-dependent RNA polymerase (RdRp). The resultant data are critical for characterizing drug distribution, bioavailability, and effective inhibition of host and viral targets. Promising lead compounds are selected on the basis of their binding energetics which have been characterized and correlated with functional activities as assessed by inhibition of RNA replication and protein synthesis. Our results reveal that the activity of heterogeneous ATA is mimicked by linear compounds of defined molecular weight, with a dichlorohexamer salicylic-acid derivative exhibiting the highest potency. These findings are instrumental for optimizing the design of structurally defined ATA analogs that fulfill the requirements of an antiviral drug with respect to bioavailability, homogeneity, and potency, thereby expanding the arsenal of therapeutic regimens that are currently available to address the urgent need for effective SARS-CoV-2 treatment strategies.

Cross-sectional Study of PONV Risk Factors for Oral Surgery After Intubated General Anesthesia With Total Intravenous Anesthesia.

OBJECTIVE: The incidence of postoperative nausea and vomiting (PONV) after general anesthesia with total intravenous anesthesia (TIVA) was reported to be significantly lower than with volatile inhalational agents (13.3% vs 25%). However, no investigation of PONV risk factors associated with TIVA has ever been reported. This cross-sectional retrospective study aimed to investigate whether known risk factors influenced PONV in intubated general anesthetics utilizing TIVA for dental or oral and maxillofacial surgery. METHODS: Subjects were 761 patients who underwent dental or oral and maxillofacial surgery under TIVA with propofol, fentanyl, and remifentanil. Univariate and multivariable logistic regression analyses were performed using PONV (within 24 hours) as the dependent variable and previously reported risk factors as independent variables. RESULTS: Age (odds ratio [OR]: 1.020 per year decrease; 95% confidence interval [CI]: 1.0002-1.0418; P = .047) and female sex (OR: 2.73; 95% CI: 1.60-4.84; P < .001) were positively associated with PONV. Sagittal split ramus osteotomy (SSRO) (OR: 2.28; 95% CI: 1.21-4.33; P = .011) and bimaxillary osteotomy (OR: 5.69; 95% CI: 2.09-15.99; P < .001) were more likely to be associated with PONV than operations that were neither bimaxillary osteotomy nor SSRO. Late PONV (2-24 hours) had an ∼2.7 times higher incidence than early PONV (0-2 hours). CONCLUSION: These findings suggest further PONV countermeasures, aside from TIVA with propofol and prophylactic antiemetics for orthognathic surgeries especially bimaxillary osteotomy, are needed.

Prolonged Washout Period for Avoiding Azilsartan-Induced Refractory Hypotension During General Anesthesia for a Patient With Renal Impairment.

Angiotensin receptor blockers (ARBs) are widely used to treat hypertension, but severe refractory hypotension during general anesthesia is a well-known complication associated with the continuation of ARBs during the perioperative period. It has therefore been recommended that ARBs be withheld for 24 hours before induction of general anesthesia. However, impaired renal function affects the pharmacokinetics of each ARB differently. The half-life of azilsartan is prolonged in accordance with the degree of renal impairment. Herein, we describe a patient with chronic kidney disease grade 3B who experienced severe refractory hypotension after induction of general anesthesia requiring administration of dopamine following inadequate responses to ephedrine and phenylephrine despite a 24-hour azilsartan washout period. When the same patient underwent general anesthesia for a subsequent surgery, azilsartan was withheld for 48 hours before induction, resulting in mild intraoperative hypotension that responded adequately to phenylephrine. Severe refractory hypotension during general anesthesia cannot always be avoided by holding azilsartan for 24 hours in patients with significant renal impairment. Therefore, a longer washout period may be preferable for patients regularly taking azilsartan who also have concurrent substantial renal impairment.

Histological observation on the initial stage of vascular invasion into the secondary ossification of murine femoral epiphyseal cartilage.

It remains unknown whether the histology of vascular invasion during secondary ossification of epiphyseal cartilage is the same as that seen in primary ossification; we examined the initial processes of vascular invasion of secondary ossification in the murine femora. Many endomucin-immunoreactive blood vessels gathered at the central region of the articular surface, and buds of soft tissue, including glomerular loops of endomucin-immunoreactive blood vessels and TNALPase- immunopositive osteoblastic cells accompanied by TRAP-positive osteoclasts, had begun to invade the epiphyseal cartilage. The invading soft tissues formed cartilage canals displaying MMP9 immunoreactivity in the tip region, and cartilaginous collagen fibrils were not visible in the vicinity of the vascular wall of the blood vessels. Thus, the histological profile marked by invading glomerular vasculature and the erosion of the cartilage matrix near the vascular walls during secondary ossification differs from that seen during primary ossification.

Additive Effects of Arsenic and Aristolochic Acid in Chemical Carcinogenesis of Upper Urinary Tract Urothelium.

BACKGROUND: Aristolochic acids (AA) and arsenic are chemical carcinogens associated with urothelial carcinogenesis. Here we investigate the combined effects of AA and arsenic toward the risk of developing upper tract urothelial carcinoma (UTUC). METHODS: Hospital-based (n = 89) and population-based (2,921 cases and 11,684 controls) Taiwanese UTUC cohorts were used to investigate the association between exposure to AA and/or arsenic and the risk of developing UTUC. In the hospital cohort, AA exposure was evaluated by measuring aristolactam-DNA adducts in the renal cortex and by identifying A>T TP53 mutations in tumors. In the population cohort, AA exposure was determined from prescription health insurance records. Arsenic levels were graded from 0 to 3 based on concentrations in well water and the presence of arseniasis-related diseases. RESULTS: In the hospital cohort, 43, 26, and 20 patients resided in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Aristolactam-DNA adducts were present in >90% of these patients, indicating widespread AA exposure. A>T mutations in TP53 were detected in 28%, 44%, and 22% of patients residing in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Population studies revealed that individuals who consumed more AA-containing herbs had a higher risk of developing UTUC in both arseniasis-endemic and nonendemic areas. Logistic regression showed an additive effect of AA and arsenic exposure on the risk of developing UTUC. CONCLUSIONS: Exposure to both AA and arsenic acts additively to increase the UTUC risk in Taiwan. IMPACT: This is the first study to investigate the combined effect of AA and arsenic exposure on UTUC.

Effect of sequence context on Polζ-dependent error-prone extension past (6-4) photoproducts.

The (6-4) pyrimidine-pyrimidone photoproduct [(6-4)PP] is a major DNA lesion induced by ultraviolet radiation. (6-4)PP induces complex mutations opposite its downstream bases, in addition to opposite 3' or 5' base, as has been observed through a site-specific translesion DNA synthesis (TLS) assay. The mechanism by which these mutations occur is not well understood. To elucidate the mechanisms underlying mutagenesis induced by (6-4)PP, we performed an intracellular TLS assay using a replicative vector with site-specific T(thymidine)-T (6-4)PP. Rev3-/-p53-/- mouse embryonic fibroblast (MEF) cells (defective in Polζ) were almost completely defective in bypassing T-T (6-4)PP, whereas both Rev1-/- and Polh-/-Poli-/-Polk-/- MEF cells (defective in Polη, Polι, and Polκ) presented bypassing activity comparable to that of wild-type cells, indicating that Y-family TLS polymerases are dispensable for bypassing activity, whereas Polζ plays an essential role, probably at the extension step. Among all cells tested, misincorporation occurred most frequently just beyond the lesion (position +1), indicating that the Polζ-dependent extension step is crucial for (6-4)PP-induced mutagenesis. We then examined the effects of sequence context on T-T (6-4)PP bypass using a series of T-T (6-4)PP templates with different sequences at position +1 or -1 to the lesion, and found that the dependency of T-T (6-4)PP bypass on Polζ is not sequence specific. However, the misincorporation frequency at position +1 differed significantly among these templates. The misincorporation of A at position +1 occurred frequently when a purine base was located at position -1. These results indicate that Polζ-dependent extension plays a major role in inducing base substitutions in (6-4)PP-induced mutagenesis, and its fidelity is affected by sequence context surrounding a lesion.

Psychometric profile of the Ages and Stages Questionnaires, Japanese translation.

BACKGROUND: This study assessed the psychometric profile of 10 questionnaires (every 6 months, from 6 to 60 months) from the Japanese translation of the Ages and Stages Questionnaires, third edition (J-ASQ-3). METHODS: Data from 439 children in a birth cohort were used to identify the J-ASQ-3 score distribution, establish cut-off scores, and calculate the instrument's internal consistency. Data were also collected from 491 outpatients to examine J-ASQ-3 test-retest reliability and concurrent validity, which was examined using the Kyoto Scale of Psychological Development (KSPD) and the Japanese version of the Denver Developmental Screening Test II (J-Denver II). Both the original and the alternative screening criteria of the ASQ-3 were used (failure in at least one and at least two domains, respectively). RESULTS: Cronbach's alpha for each J-ASQ-3 subscale on each questionnaire ranged from 0.45 to 0.89. Test-retest reliability was >0.75 for the subscales on almost all questionnaires. Concurrent validity was also adequate. In comparison with the screening results of the KSPD, the overall sensitivity and specificity were 96.0% and 48.8%, respectively, when the ASQ-3 original criterion was used, and 92.1% and 74.9%, respectively, when the alternative criterion was used. In comparison with the screening results of the J-Denver II, the overall sensitivity and specificity were 75.6% and 74.7%, respectively, when the ASQ-3 original criterion was used, and 56.3% and 93.0%, respectively, when the alternative criterion was used. CONCLUSIONS: This study quantified the psychometric profiles of the Japanese translations of 10 ASQ-3 questionnaires. We demonstrated the validity of the J-ASQ-3 and determined new cut-off scores. Further studies with larger samples from a greater range of locations are required to clarify the suitability of this tool for all Japanese children.

Motor and cognitive development of children with Down syndrome: The effect of acquisition of walking skills on their cognitive and language abilities.

OBJECTIVE: This study investigated the relationship between motor and cognitive/language development in children with Down syndrome (DS). We also tested the hypothesis that acquisition of walking skills facilitates later cognitive/language development. METHODS: Participants were 156 children with DS who were less than 48 months old and had undergone a health checkup by medical doctors and received rehabilitation treatment between April 2013 and March 2017 in Yokohama, Japan. To assess their development, the Kyoto Scale of Psychological Development (KSPD) 2001 was used, which measures development in three subdomains: Posture-Motor (P-M), Cognitive-Adaptive (C-A), and Language-Social (L-S). To investigate the relationship between motor and cognitive/language development, partial correlation analyses were conducted that controlled for participants' age. To test the effect of achieving walking skills, regression analyses were conducted using only data from participants who took the KSPD at least twice and could not walk at the initial test. RESULTS: P-M developmental age (DA) was significantly and positively correlated with both C-A DA and L-S DA in children 1-3 years old. The relationship strengthened with increased age. Acquisition of walking skills had a significant positive effect on both the C-A DA and L-S DA at the second test when controlling for the C-A DA and L-S DA at the first test and age at the second test. CONCLUSION: Motor development was correlated with both cognitive and language development in young children with DS. Results also suggested that achievement of walking could facilitate later cognitive/language development in children with DS.

Hospitals' Preparedness to Treat Pediatric Patients During Mass Casualty Incidents.

OBJECTIVES: Little is known about the preparedness of hospitals to care for pediatric patients during a major incident in Japan. This study assessed the disaster preparedness of a children's hospital in Japan by using a disaster drill.Materials and MethodsWe performed a triage drill with all hospitalized patients. The triage tags and medical records were reviewed retrospectively. We determined the efficacy of triage education, the validity of the Simple Triage and Rapid Treatment (START) method for children, and the potential need for evacuation through the disaster drill. RESULTS: This study highlights 3 important issues about the hospital's preparedness. First, it is difficult to promote disaster education for staff who are not well trained on handling disasters. Second, the START method is suitable for children older than 5 years, but it has a high rate of over-triaging among younger children. Third, approximately 40% of patients who are coded as immediate may require transportation resources in a hospital evacuation. CONCLUSIONS: Our findings suggest that disaster preparedness, such as educating hospital staff regarding disasters and establishing evacuation systems for a number of pediatric patients when a disaster happens, is essential for caring for hospitalized children during a mass casualty incident. (Disaster Med Public Health Preparedness. 2019;13:429-432).

Titanium(iv) oxide having a copper co-catalyst: a new type of semihydrogenation photocatalyst working efficiently at an elevated temperature under hydrogen-free and poison-free conditions.

A copper-loaded titanium(iv) oxide photocatalyst exhibited perfect selectivity in hydrogenation of alkynes to alkenes in an alcohol solution at 298 K under hydrogen-free and poison-free conditions. A slight elevation in the reaction temperature to 323 K greatly increased the reaction rate with the selectivity being preserved and the formation of an H2 by-product being suppressed. The apparent activation energy of 4-octyne semihydrogenation was determined to be 54 kJ mol-1, indicating that the rate determining step of this photocatalytic reaction was not an electron production process but a thermocatalytic hydrogenation process under light irradiation.

Developmental outcomes of Japanese children born through Assisted Reproductive Technology (ART) in toddlerhood.

AIM: This study aimed to investigate developmental outcomes of Japanese babies born through Assisted Reproductive Technology (ART) at ages 2 and 3. METHODS: The data were gathered from 1085 children in a hospital-based cohort study conducted in Japan. The children's level of development was assessed through a parent-rated questionnaire, the Kinder Infant Development Scale, which consists of nine developmental domains. We compared the development of children born through ART and those born naturally by conducting analyses of covariance. For the analyses, the effect of maternal age, family income, parental education and multiple birth were controlled for. RESULTS: At 24 months, no significant difference was found between children born through ART and those born naturally in development in any domain. At 36 months, a significant difference was found in development of Receptive language (F (1, 845) = 6.148, P = 0.013), Expressive language (F (1, 845) = 4.060, P = 0.044) and Language concept (F (1, 845) = 6.968, P = 0.008). For these domains, children born through ART had a significantly higher developmental age compared to children born naturally. CONCLUSION: At age 2, no significant difference was found between the children born through ART and those born naturally in nine developmental domains, although at age 3, the children born through ART showed significantly better language development than the children born naturally.

Development of a new screening tool for neuromotor development in children aged two - the neuromotor 5 min exam 2-year-old version (N5E2).

OBJECTIVE: As a new screening tool for neuromotor development in children aged two, we developed the Neuromotor 5 min Exam 2-year-old version (N5E2), which can be easily administered by pediatricians or primary care physicians. In this study, as an initial attempt to examine the utility of the N5E2, the inter-rater reliability on scoring for the individual items in this scale was assessed. METHODS: The participants of the study were 29 children (aged 1-5 years, mean age = 2.79) diagnosed with a variety of neuromotor/developmental disorders/high-risk conditions. Inter-rater reliability was examined on the following 11 items in the N5E2: (1) Retrieving a rolling ball, (2) Gait, (3) Toe-walking, (4) Asymmetries of posture and/or movement, (5) Age at unsupported walking, (6) Speaking in two-word understandable sentences, (7) Hypotonus, (8) Hypertonus, (9) Eye movement, (10) Vision problem, (11) Hearing problem. The items were administered to children by two pediatricians with different expertise and clinical experience, separately. RESULTS: The results showed that among the eleven items in the N5E2 examined, a high level of agreement (κ ≥ 0.60) was found on 4 items, and a moderate level of agreement (0.40 ≤ κ < 0.60) was found on 5 items. The level of agreement somewhat improved after the dichotomization of the score; using this format, a high level of rater agreement (κ ≥ 0.60) was found on 6 out of 11 items. The analyses also revealed high inter-rater reliability on the sum score of the 11 items (r = 0.84). CONCLUSIONS: The results suggest the possibility that this brief screening tool could be feasible in settings where clinicians' experience varies, based on its inter-rater reliability on individual items between the clinicians with different expertise and amount of clinical experiences.

Developmental trend of children with Down's syndrome - How do sex and neonatal conditions influence their developmental patterns?

OBJECTIVE: This study investigated factors that would influence developmental trend of children with Down's syndrome (DS) in three different domains (motor, cognitive, language), specifically focusing on the effect of sex and neonatal conditions, including preterm birth, low birth weight, and congenital heart disease (CHD). METHODS: The participants were 158 children with DS (mean age at the initial test = 25.5 months) receiving clinical service at a rehabilitation center in Yokohama, Japan. Kyoto Scale of Psychological Development was used to measure developmental level, which derive total developmental age (DA), Posture-motor DA, Cognitive-adaptive DA, and Language-social DA. For the analyses, a multilevel model for change was adopted, as the model allowed us to investigate intrapersonal growth and the between-personal factors that are associated with individual differences in the pattern of growth. RESULTS: The developmental speed of children with DS was found to be slower than that of typical children in all the three developmental domains assessed (i.e., the estimated coefficient of the slope for chronological age on DA was less than 1). DS Girls developed significantly faster than boys in non-verbal cognitive and language abilities. Low birth weight and CHD had a significant negative impact on development of non-verbal cognitive abilities for boys, but had a somewhat positive effect for girls. CONCLUSION: As was shown in previous studies, the result of this study indicated that the children with DS develop slower than non-disabled children. Low birth weight and CHD were found to influence developmental trend of children with DS, differently for boys and girls.

Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions.

Endogenous DNA damage is causally associated with the functional decline and transformation of stem cells that characterize aging. DNA lesions that have escaped DNA repair can induce replication stress and genomic breaks that induce senescence and apoptosis. It is not clear how stem and proliferating cells cope with accumulating endogenous DNA lesions and how these ultimately affect the physiology of cells and tissues. Here we have addressed these questions by investigating the hematopoietic system of mice deficient for Rev1, a core factor in DNA translesion synthesis (TLS), the postreplicative bypass of damaged nucleotides. Rev1 hematopoietic stem and progenitor cells displayed compromised proliferation, and replication stress that could be rescued with an antioxidant. The additional disruption of Xpc, essential for global-genome nucleotide excision repair (ggNER) of helix-distorting nucleotide lesions, resulted in the perinatal loss of hematopoietic stem cells, progressive loss of bone marrow, and fatal aplastic anemia between 3 and 4 months of age. This was associated with replication stress, genomic breaks, DNA damage signaling, senescence, and apoptosis in bone marrow. Surprisingly, the collapse of the Rev1Xpc bone marrow was associated with progressive mitochondrial dysfunction and consequent exacerbation of oxidative stress. These data reveal that, to protect its genomic and functional integrity, the hematopoietic system critically depends on the combined activities of repair and replication of helix-distorting oxidative nucleotide lesions by ggNER and Rev1-dependent TLS, respectively. The error-prone nature of TLS may provide mechanistic understanding of the accumulation of mutations in the hematopoietic system upon aging.

Photocatalytic hydrogenation of furan to tetrahydrofuran in alcoholic suspensions of metal-loaded titanium(iv) oxide without addition of hydrogen gas.

The use of metal co-catalysts broadens the application of photocatalytic reduction without the use of dihydrogen (H2) gas. We examined photocatalytic hydrogenation of furan, a representative heterocyclic compound and a compound derived from biomass, in alcoholic suspensions of metal-loaded titanium(iv) oxide (TiO2) under a H2-free condition and we found that furan was almost quantitatively hydrogenated to tetrahydrofuran with a high apparent quantum efficiency of 37% at 360 nm when palladium was used as a co-catalyst. Effects of different metal co-catalysts, different amounts of the co-catalyst, the type of TiO2, the type of alcohol, light wavelength and reusability for furan hydrogenation were investigated. Based on the results, the functions of TiO2 and the co-catalyst and the reaction process are discussed.