Track-etched membrane-based dual-electrode coulometric detector for microbore/capillary high-performance liquid chromatography

The electrochemical flow cell containing track-etched microporous membrane electrodes was applied to a dual-electrode coulometric detector for microbore/capillary HPLC with a small injection volume and low eluent flow rate. The proposed flow cell with a 0.1-mm diameter inlet channel gave a detection volume of 0.08 nL per electrode, which was determined by the eluent flow through the electrode. For the dual-electrode detector, the calculated volume was 0.24 nL. The efficiency of electrooxidation of L-ascorbic acid increased as the flow rate decreased and was close to 100% when the flow rate was below 50 µL min−1, which is a common flow rate in microbore or capillary liquid chromatography. Catecholamines, such as noradrenaline, adrenaline, and dopamine, were detected by total conversion with two-electron oxidation in the potential range from 0.8 to 1.0 V vs. Ag/AgCl after separation with a microbore column. These peaks were accompanied by corresponding cathodic peaks derived from quasi-stable electrooxidation products of the catecholamines. The detection limits of noradrenaline, adrenaline, and dopamine were 0.1, 0.1, and 0.2 μM, respectively. The RSD values for five replicate measurements of 5.0 μM of these compounds were 0.9%, 0.7%, and 1.5%, respectively. Coulometric detection was also demonstrated by determination of catecholamines in pharmaceuticals

Why Are COVID-19 Mortality Rates by Country or Region So Different?: An Ecologic Study of Factors Associated with Mortality from Novel Coronavirus Infections by Country

[Background] In order to find out the factors associated with the large disparities in COVID-19 mortality rates by country, we conducted an ecological study by linking existing statistics. In Japan, a large variation was observed in between geographical areas when assessing mortality. We performed a regional correlation analysis to find factors related to regional mortality. [Methods] This study design was an ecologic study. A multiple regression analysis was performed with COVID-19 mortality rates of different countries as the dependent variable together with various health care and economic factors. We calculated the cumulative mortality rate as of June 30, 2020. For the regional correlation analysis of Japan, 47 prefectures were divided into nine regions. The factors examined were health care and tourism. Data for 33 Organization for Economic Co-operation and Development (OECD) countries were analyzed. In Japan’s regional analysis, the whole country was classified into nine regions. [Results] Factors related to mortality were the incidence of Kawasaki disease (KD), number of computed tomographies (CTs), and alcohol consumption. Mortality was low in countries with high incidence of KD and high number of CTs, as well as in countries with high alcohol consumption. In European countries, high smoking prevalence and a high Gini coefficient were positively related to high mortality. According to a regional analysis in Japan, mortality was related to proportion of population in the densely inhabited districts, the number of foreign visitors per capita, and the number of Chinese visitors per capita. [Conclusion] Low mortality in East Asia was associated with specific disease morbidity (KD), alcohol consumption, and CT numbers. It was suggested that the mortality gap in Japan was related to the number of foreign tourists and the proportion of population in the densely inhabited districts

Developmental Changes of Prefrontal Activation in Humans: A Near-Infrared Spectroscopy Study of Preschool Children and Adults

Previous morphological studies indicated that development of the human prefrontal cortex (PFC) appears to continue into late adolescence. Although functional brain imaging studies have sought to determine the time course of functional development of the PFC, it is unclear whether the developmental change occurs after adolescence to adulthood and when it achieves a peak because of the narrow or discontinuous range in the participant's age. Moreover, previous functional studies have not focused on the anterior frontal region, that is, the frontopolar regions (BA9/10). Thus, the present study investigated the developmental change in frontopolar PFC activation associated with letter fluency task by using near-infrared spectroscopy (NIRS), in subjects from preschool children to adults. We analyzed the relative concentration of hemoglobin (ΔHb) in the prefrontal cortex measured during the activation task in 48 typically-developing children and adolescents and 22 healthy adults. Consistent with prior morphological studies, we found developmental change with age in the children/adolescents. Moreover, the average Δoxy-Hb in adult males was significantly larger than that in child/adolescent males, but was not true for females. These data suggested that functional development of the PFC continues into late adolescence. Although the developmental change of the frontopolar PFC was independent of gender from childhood to adolescence, in adulthood a gender difference was shown

Suicide rates during social crises: Changes in the suicide rate in Japan after the Great East Japan earthquake and during the COVID-19 pandemic

We aimed to observe the changes in suicide rates after the Great East Japan Earthquake and during the coronavirus (COVID-19) pandemic, as typical cases of social crises, in Japan. A descriptive epidemiological study was conducted using data on the number of deaths by suicide published by the National Police Agency. The suicide rate ratio during the crisis—the monthly suicide mortality rate in the year of the crisis divided by the average suicide mortality rate in the three years before the crisis—was used as the indicator. After the earthquake, in March 2011 the suicide rate was 18% lower than the average mortality rate for the previous three years. However, it increased by 18% in May and 8% in June; increased mortality was observed among women. The suicide rate began to decline after October 2011. During the COVID-19 pandemic, the suicide rate decreased from February to June 2020. The declines in April and May were significant at 20% and 18%, respectively. From July onwards, the suicide rate of women began to rise, and from October, the overall suicide also began to increase. The rise in female suicide rates was significant, especially in October, with an increase of 70%. Thus, during these crises, suicide rates fell temporarily but then rose, especially among women. The period of increase in suicide rates was longer during the COVID-19 pandemic than after the earthquake. Therefore, there is an urgent need to promote measures for suicide prevention currently, and during a future crisis

Facile one-pot access to π-conjugated polymers via sequential bromination/direct arylation polycondensation

The synthesis of π-conjugated polymers starting from unfunctionalized aromatic monomers via sequential bromination/direct arylation polycondensation was investigated. The developed protocol provides a step-economical access to the polymers in a one-pot fashion, without the need for prior preparation and purification of dibrominated aromatic monomers or organometallic monomers. Benzyltrimethylammonium tribromide was effective for the bromination of 10-(2-octyldodecyl)phenothiazine and 4,4′-didodecyl-2,2′-bithiophene, and the obtained dibrominated aromatic monomers were used for the subsequent direct arylation polycondensation without isolation and purification. The direct arylation polycondensation reaction yielded the corresponding donor–acceptor-type π-conjugated polymers in moderate to good yields. The sequential protocol was also applicable to the synthesis of poly(3-hexylthiophene-2,5-diyl) from 3-hexylthiophene. The obtained polymers served as semiconducting materials in organic light-emitting diodes and organic photovoltaics

Phase competitions and coexistences in quasi-one-dimensional molecular conductors: exact diagonalization study

We investigate ground state properties of a quasi-one-dimensional electron-lattice coupled model for quarter-filled molecular conductors. The effective one-dimensional extended Hubbard model coupled to adiabatic lattice degree of freedom is derived by the inter-chain mean-field approximation and solved by Lanczos exact diagonalization method. We find that the critical behavior among lattice tetramerized states with different charge-lattice ordered patterns is sensitively affected by the inter-chain Coulomb interaction, lattice anharmonicity, and intrinsic dimerization. This indicates a subtle balance between these states originating from strong correlation and reduced dimensionality

Association of Genetic Risks with Autism Spectrum Disorder and Early Neurodevelopmental Delays among Children without Intellectual Disability

IMPORTANCE Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood. OBJECTIVE To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. MAIN OUTCOMES AND MEASURES Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months. RESULTS Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; β, 0.71; SE, 0.24; P = .03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; β, −1.25; SE, 0.39; P = .01) and receptive language (R2 = 0.014; β, −1.19; SE, 0.39; P = .02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; β, −5.28; SE, 1.40; P \u3c .001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; β, −5.30; SE 1.30; P \u3c .001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; β, −6.04; SE, 1.75; P = .001; regulation of monocyte differentiation: R2 = 0.052; β, −6.63; SE, 1.90; P = .001; and B-cell differentiation: R2 = 0.051; β, 7.37; SE, 2.15; P = .001); glutamatergic signaling–associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; β, −5.82; SE, 1.68; P = .001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; β, 3.54; SE, 1.09; P = .001; and negative regulation of glutamate secretion: R2 = 0.045; β, −5.38; SE, 1.74; P = .002). CONCLUSIONS AND RELEVANCE In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills

Effectiveness of Screening and Brief Alcohol Intervention at the Workplace: A Study Protocol for a Randomized Controlled Trial at Five Japan-Based Companies

Background: Despite evidence regarding the effectiveness of screening and brief interventions for excessive alcohol use in primary care, these tools are not a part of routine practice. It has been suggested that using these tools at the workplace may be critical to alcohol-associated harm; however, evidence for this claim is unclear. The aim of this article is to develop a study protocol which evaluates the effect of brief alcohol intervention at the workplace to reduce harmful alcohol drinking. Methods: A randomized controlled trial involving employees (aged 20–74 years) of five Japan-based companies who were screened “positive” by Alcohol Use Disorder Identification Test (AUDIT) is on-going. Participants were randomized into “Patient Information Leaflet” (control group), “Brief Advice and Counselling,” and “Five-minute Brief Advice” groups. A self-administered questionnaire was used to assess alcohol consumption, lifestyle behavior, health status, work performance, and consequences of alcohol use. Data of laboratory markers were collected from routine health checkups.Results: A total of 351 participants were randomized into Patient Information Leaflet (n = 111), Brief Advice and Counselling (n = 128), and Five-minute Brief Advice (n = 112) groups. Participants were mostly men with a median age of 49 years. Median AUDIT score and weekly alcohol consumption were 11 points and 238 g/week, respectively. Two-thirds of the participants were manufacturing workers. Conclusion: This study protocol developed the first trial in Japan to investigate the effect of brief alcohol intervention combined with a recommended screening tool at the workplace. Our findings can provide evidence on the effectiveness and relevance of these tools to occupational health

Heat-not-burn tobacco, electronic cigarettes, and combustible cigarette use among Japanese adolescents: a nationwide population survey 2017

Background: From among the global public health concerns, smoking remains one of the most crucial challenges. Especially for adolescents, the increase in the use of electronic cigarettes is controversial, as its use may lead to established smoking. In Japan, where a unique tobacco regulation system exists, the heat-not-burn tobacco market has been growing. However, the prevalence and association of combustible cigarettes and new tobacco-related products have not yet been closely investigated among Japanese adolescents. This study aimed to clarify the prevalence of smoking among adolescents, including new types of tobacco-related products, and to compare the characteristics of their users. Methods: The 2017 Lifestyle Survey of Adolescents is a nationally-representative survey collected in Japan. From the national school directory, 98 junior high schools and 86 high schools were randomly sampled throughout Japan. The students completed an anonymous questionnaire at school. We calculated the prevalence of use for each type of tobacco product. Then, the use of a combination of products and the characteristics of different types of products were examined. Results: In total, 64,152 students from 48 junior high schools and 55 high schools were included the analysis (school response rate = 56%, Mage = 15.7 years, 53.9% boys). The age-adjusted rate of ever (current) use of electronic cigarettes was 2.1% (0.7%) in junior high school and 3.5% (1.0%) in high school; that of combustible cigarettes was 2.6% (0.6%) in junior high school and 5.1% (1.5%) in high school. The rate of heat-not-burn tobacco use was lower relative to other products: 1.1% (0.5%) in junior high school and 2.2% (0.9%) in high school. An examination of the combined use of the three products identified a high number of dual users. Comparisons between different types of users indicated different backgrounds for combustible cigarette users and new product users. Conclusions: The prevalence of new tobacco-alternative products is growing in popularity among Japanese adolescents. Dual use is common, and many adolescents use new products only. Moreover, e-cigarettes might attract a broader range of groups to smoking. Continuous monitoring and research are needed to investigate their influence as a possible gateway to tobacco smoking