Trends in prescription of anti-seizure medicines for Japanese pediatric outpatients during 2013-2019.

Temporal trends in prescriptions of anti-seizure medicines (ASMs) for children, including newer ASMs, are unclear. We investigated ASM prescription trends for pediatric outpatients in Japan. The MDV analyzer® was used to analyze the MDV database containing de-identified hospital administrative data. Administrative data as of June 2021 including pediatric outpatients (0-17 years) with epilepsy, visiting 123 acute diagnostic procedure combination hospitals during 2013-2019, were used. Annual ASMs prescription trends were calculated, based on proportions. The Cochran-Armitage trend test evaluated the proportion of prescriptions for each ASM. ASMs most often prescribed were valproic acid, carbamazepine, and levetiracetam, regardless of sex. In girls, the proportion of valproic acid and carbamazepine prescriptions decreased from 37.93% to 26.84%, and from 24.80% to 15.78%, respectively (p < 0.0001). Conversely, the proportion of levetiracetam prescriptions increased from 6.40% to 28.18% (p < 0.0001). In boys, the proportion of valproic acid and carbamazepine prescriptions decreased, from 36.58% to 32.20% and from 26.42% to 16.85%, respectively (p < 0.0001). The proportion of levetiracetam prescriptions increased from 5.64% to 23.02% (p < 0.0001). Overall, the proportion of valproic acid and carbamazepine prescriptions declined, whereas levetiracetam prescriptions increased. Trends in ASM prescriptions among pediatric outpatients with epilepsy in Japan have shifted towards more recently available ASMs.

Drug prescription for attention deficit hyperactivity disorder drugs in pediatric outpatients: A retrospective survey of Japanese administrative data (2012-2018).

We aimed to clarify the prescription trend of ADHD drugs in Japanese pediatric outpatients. From January 2012 to December 2018, we evaluated the trends of prescribing methylphenidate-osmotic-controlled release oral delivery system (OROS), atomoxetine, and guanfacine as monotherapy. In boys, methylphenidate-OROS and atomoxetine prescriptions decreased from 46.5 % to 37.2 % and 18.6 % to 15.6 %, respectively. Prescriptions of guanfacine increased from 0.0 % to 12.3 %. In girls, the methylphenidate-OROS prescriptions was not significantly different (37.0 % to 26.4 %); however, atomoxetine decreased from 23.1 % to 16.3 %, and guanfacine increased from 0.0 % to 12.8 %. Methylphenidate-OROS and atomoxetine prescriptions changed to guanfacine between 2012 and 2018.

An α-Lipoic acid derivative, and anti-ROS agent, prevents the acquisition of multi-drug resistance in clinical isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most common causes of nosocomial infections, and its multi-drug resistance has been a serious problem worldwide. The aim of this study was to evaluate whether exposure to piperacillin and reactive oxygen species (ROS) could lead to multi-drug resistance for clinical isolates of P. aeruginosa. The inhibition of this acquired resistance by the anti-ROS agent was also examined. In vitro inducement of multi-drug resistance was performed against 20 clinical isolates. These strains were incubated for 24 h and transferred 5 times after being exposed to 1 mM H2O2 (ROS) in addition to a sub-MIC of piperacillin by the agar dilution method. Each MIC of piperacillin and levofloxacin was determined. As the mechanism of levofloxacin resistance, mutation of QRDR was investigated. The expression level of genes encoding efflux pumps; mexA, mexY, mexC, and D2 porin; oprD were determined by real-time PCR. Multi-resistance to both piperacillin and levofloxacin was induced with 4 of 20 strains (20%). No amino acid change was confirmed in QRDR. These strains showed overexpression of mexA, mexY, mexC, and another one showed decrease of oprD expression. Resistance development in 4 strains was inhibited by the same method including the anti-ROS agent, sodium zinc histidine dithiooctanamide (DHL-His-Zn). In conclusion, stimulation by ROS promoted acquisition of multi-drug resistance in 20% of isolates of P. aeruginosa, and DHL-His-Zn completely inhibited this acquisition of resistance. Therefore, this anti-ROS agent may be useful to assist antimicrobial chemotherapy by preventing multi-drug resistance.

Prevalence of allergic rhinitis based on the SACRA questionnaire among Japanese nursing professionals with asthma.

Although adult asthma is attributable to occupational factors and asthma and rhinitis are related, relatively few studies have investigated the prevalence of occupational rhinitis based on occupation, and knowledge of occupational rhinitis in Japan is currently limited. The objective of this cross-sectional study was to estimate the prevalence of allergic rhinitis among Japanese nursing professionals with asthma. A postal survey was conducted from October to December 2013 using translated versions of the European Community Respiratory Health Survey for the prevalence of asthma and State of the Impact of Allergic Rhinitis on Asthma Control questionnaire for the prevalence of rhinitis. Of 4,634 Japanese nursing professionals, 497 subjects had asthma, and 270 of these 497 subjects had allergic rhinitis (54.3%; 95% confidence interval [CI], 49.7-58.7). Latex allergy was significantly associated with allergic rhinitis (odds ratio, 1.77; 95% CI, 1.21-2.60). There was no relationship between employment period and prevalent allergic rhinitis. The results of this study provide fundamental information regarding occupational health among Japanese nursing professionals, including the prevalence of allergic rhinitis among Japanese nursing professionals with asthma and latex allergy as a potential risk factor for prevalent allergic rhinitis.

Conserved evolutionary history for quick detection of threatening faces.

Humans quickly recognize threats such as snakes and threatening faces, suggesting that human ancestors evolved specialized visual systems to detect biologically relevant threat stimuli. Although non-human primates also detect snakes quickly, it is unclear whether primates share the efficient visual systems to process the threatening faces of their conspecifics. Primates may not necessarily process conspecific threats by facial expressions, because threats from conspecifics in natural situations are often accompanied by other cues such as threatening actions (or attacks) and vocal calls. Here, we show a similar threat superiority effect in both humans and macaque Japanese monkeys. In visual search tasks, monkeys and humans both responded to pictures of a threatening face of an unfamiliar adult male monkey among neutral faces faster than to pictures of a neutral face among threatening faces. However, the monkeys' response times to detect deviant pictures of a non-face stimulus were not slower when it was shown among threat faces than when it was shown among neutral faces. These results provide the first evidence that monkeys have an attentional bias toward the threatening faces of conspecifics and suggest that threatening faces are evolutionarily relevant fear stimuli. The subcortical visual systems in primates likely process not only snakes, but also more general biological threat-relevant stimuli, including threatening conspecific faces.

Asthma and Wheeze Prevalence among Nursing Professionals in Western Japan: A Cross-Sectional Study.

Although adult asthma is attributable to occupational factors, few reports are available on asthma prevalence among health care workers in Japan. The objective of this study was to estimate the prevalence of asthma and wheeze among Japanese nursing professionals. A cross-sectional study was conducted by postal survey using a translated version of the European Community Respiratory Health Survey questionnaire from April to June 2013. The analysis included 4634 nursing professionals (257 men and 4377 women) and the overall response rate was 84.8%. The prevalence of current asthma and wheeze were 10.7% (95% confidence interval (CI), 9.9%-11.7%) and 15.6% (95% CI, 14.5%-16.6%), respectively. More than one year of work experience as a nursing professional and more than one year of experience with bed-making tasks were associated with odds ratios (ORs) of 1.95 (95% CI, 1.12-3.39) and 1.64 (95% CI, 1.15-2.23) for wheeze, respectively. Current smoking was significantly associated with the presence of wheeze, with ORs of 2.27 for men (95% CI, 1.11-4.64) and 2.01 for women (95% CI, 1.54-2.64). Among female nurses, latex allergy was associated with wheeze (OR, 1.87; 95% CI, 1.56-2.23), as was body mass index ≥30 (OR, 2.76; 95% CI, 1.65-4.62). This study has provided the prevalence of asthma and wheeze among Japanese nursing professionals. Employment period, bed-making tasks, latex allergy, obesity, and smoking may be risk factors for prevalent wheeze among nursing professionals.

Antimicrobial efficacy of combined clarithromycin plus daptomycin against biofilms-formed methicillin-resistant Staphylococcus aureus on titanium medical devices.

In vitro efficacy of combined eradication therapy with clarithromycin and daptomycin against biofilm-formed methicillin-resistant Staphylococcus aureus on the orthopedic titanium devices was evaluated. The bactericidal effect of this antibiotic was investigated by a re-culture test, the scanning electron microscopy, and fluorescence microscopy using a double-staining dyes. Clarithromycin decreased the amount to half in 24 h. Although MRSA biofilms were not eradicated with clarithromycin or daptomycin alone, clarithromycin combined with daptomycin was useful to sterilize titanium devices within 72 h. This in vitro study showed that combined treatment with clarithromycin plus daptomycin is useful to eradicate staphylococcal biofilms formed on orthopedic devices.

[BASELINE SCREENING USING INTERFERON-GAMMA RELEASE ASSAY SUGGESTS AN INCREASED RISK OF MYCOBACTERIUM TUBERCULOSIS INFECTION AMONG EMPLOYEES IN A JAPANESE GENERAL HOSPITAL].

OBJECTIVES: This retrospective study aimed to assess the risk of tuberculosis infection for the employees of a Japanese hospital using baseline interferon-gamma release assay (IGRA). The risk was defined as exposure to the hospital environment. METHODS: In total, 870 hospital employees including 161 new employees, 582 for baseline assay, and 127 for contact examination (709 subjects in the post-employment group) were examined from December 2010 to April 2012. The new employees were considered as the "non-exposure" group, whereas the post-employment group was considered as the "exposure" group. Multiple logistic regression analyses were used to calculate the odds ratio (OR) for IGRA positivity, adjusted for gender, smoking history, and alcohol intake (model 1), and for years of employment (model 2). RESULTS: The exposure group was significantly associated with an increased risk of positive IGRA results, even when adjusted for years of employment (OR: 4.1; 95% confidence interval: 1.4-17.6; P = 0.007). Subgroup analyses stratified by profession indicated a significantly increased OR for laboratory technicians, doctors, and nurses in both models. No correlation was observed between the length of employment and IGRA positivity. CONCLUSION: Exposure to the hospital environment increased the risk of tuberculosis infection for employees irrespective of the length of employment. Laboratory technicians, doctors, and nurses were at the highest risk of infection.

The convergent evolution of blue iris pigmentation in primates took distinct molecular paths.

How many distinct molecular paths lead to the same phenotype? One approach to this question has been to examine the genetic basis of convergent traits, which likely evolved repeatedly under a shared selective pressure. We investigated the convergent phenotype of blue iris pigmentation, which has arisen independently in four primate lineages: humans, blue-eyed black lemurs, Japanese macaques, and spider monkeys. Characterizing the phenotype across these species, we found that the variation within the blue-eyed subsets of each species occupies strongly overlapping regions of CIE L*a*b* color space. Yet whereas Japanese macaques and humans display continuous variation, the phenotypes of blue-eyed black lemurs and their sister species (whose irises are brown) occupy more clustered subspaces. Variation in an enhancer of OCA2 is primarily responsible for the phenotypic difference between humans with blue and brown irises. In the orthologous region, we found no variant that distinguishes the two lemur species or associates with quantitative phenotypic variation in Japanese macaques. Given the high similarity between the blue iris phenotypes in these species and that in humans, this finding implies that evolution has used different molecular paths to reach the same end.

Human young children as well as adults demonstrate 'superior' rapid snake detection when typical striking posture is displayed by the snake.

Humans as well as some nonhuman primates have an evolved predisposition to associate snakes with fear by detecting their presence as fear-relevant stimuli more rapidly than fear-irrelevant ones. In the present experiment, a total of 74 of 3- to 4-year-old children and adults were asked to find a single target black-and-white photo of a snake among an array of eight black-and-white photos of flowers as distracters. As target stimuli, we prepared two groups of snake photos, one in which a typical striking posture was displayed by a snake and the other in which a resting snake was shown. When reaction time to find the snake photo was compared between these two types of the stimuli, its mean value was found to be significantly smaller for the photos of snakes displaying striking posture than for the photos of resting snakes in both the adults and children. These findings suggest the possibility that the human perceptual bias for snakes per se could be differentiated according to the difference of the degree to which their presence acts as a fear-relevant stimulus.

Skewed matrilineal genetic composition in a small wild chimpanzee community.

Maternal kinship is important in primate societies because it affects individual behaviour as well as the sustainability of populations. All members of the Bossou chimpanzee community are descended from 8 individuals (herein referred to as original adults) who were already adults or subadults when field observations were initiated in 1976 and whose genetic relationships were unknown. Sequencing of the control region on the maternally inherited mtDNA revealed that 4 (1 male and 3 females) of the 8 original adults shared an identical haplotype. We investigated the effects of the skewed distribution of mtDNA haplotypes on the following two outcomes. First, we demonstrated that the probability of mtDNA haplotype extinction would be increased under such a skewed composition in a small community. Second, the ratio of potential mating candidates to competitors is likely to decrease if chimpanzees become aware of maternal kinship and avoid incest. We estimated that the magnitude of the decrease in the ratio is 10 times greater in males than in females. Here we demonstrate a scenario in which this matrilineal skewness in a small community accelerates extinction of mtDNA haplotype, which will make it more difficult to find a suitable mate within the community.

Male-female mating tactics and paternity of wild Japanese Macaques (Macaca fuscata yakui).

For Japanese macaques, visits by nontroop males (NTMs) often diminish the immediate copulation success of high-ranking males, although few studies have conducted a genetic analysis to show their contribution to the gene pool. I used noninvasively collected samples of semen, blood, urine and feces for the analysis of paternity in nine offspring born in two troops living on the island of Yakushima, Japan. I found that five of the nine offspring were sired by NTMs. It is argued that social change, small troop size and the timing of conception are all factors contributing to the NTM's reproductive success.

Food conditions, competitive regime, and female social relationships in Japanese macaques: within-population variation on Yakushima.

Feeding conditions, competitive regime, and female social relationships of Japanese macaques (Macaca fuscata) on Yakushima were compared between the two habitats at two different altitudes (coniferous forest, 1,000-1,200 m and coastal forest, 0-200 m). Fruit availability was higher in the coastal forest. There was no consistent difference in the frequency of agonistic interactions within a group during feeding between the two habitats. The coastal forest evoked stronger inter-group contest competition compared to the coniferous forest as evidenced by a higher inter-group encounter rate and a higher proportion of aggressive encounters to non-aggressive ones. Birth rate was higher in larger groups compared to smaller ones in the coastal forest, but did not differ in the coniferous forest. In spite of these differences in competitive regime, no variation in female social relationships was observed, such as direction and concentration on particular individuals in grooming, linearity in dominance rank, counter-attack, and support of juvenile kin during agonistic interactions. The present results indicate that the female social relationships of Japanese macaques are robust and do not change according to changes in the current environment.

Comparisons of food availability and group density of Japanese macaques in primary, naturally regenerated, and plantation forests.

We compared food availability and group density of Japanese macaques in Yakushima, southern Japan, among primary forest and two habitats that had been disturbed by logging and had different regeneration histories. The study was conducted in an undisturbed national park, forest that was logged 7-18 years ago and later naturally regenerated, and forest that was logged 19-27 years ago and later planted with Japanese cedar (Cryptomeria japonica) trees. The plantation forest was primarily composed of large Cryptomeria japonica trees at low stand density, while the naturally regenerated forest was composed of many small trees. The total basal area and number of trees in the primary forest were comparable to those in the plantation forest. Annual fruit production was greatest in the naturally regenerated forest, intermediate in the primary forest, and negligible in the plantation forest. Herb availability was high in the naturally regenerated forest, but low in the primary and plantation forests. The group density of Japanese macaques was high in the naturally regenerated forest, intermediate in the primary forest, and low in the plantation forest. Since group size in the naturally regenerated forest was small, individual density was almost the same as in the primary forest. These results suggest that the effects of regeneration on macaques vary between the two habitats. The plantation forest consisted mostly of Cryptomeria japonica, which supplies only flowers as food in a limited season, and had a lower density of macaques. On the other hand, in the naturally regenerated forest, fruit production and herb availability were high (probably because of the enhanced light conditions after logging), and the density of macaques was as high as in the primary forest.

Mitochondrial DNA genealogy of chimpanzees in the Nimba mountains and Bossou, West Africa.

The chimpanzee populations of the Bossou and Nimba regions in West Africa were genetically surveyed to 1) reveal the genetic relationship between the Bossou and Nimba populations, and 2) elucidate the evolutionary relationship between the Bossou-Nimba and other West African populations. The chimpanzee group at Bossou is characterized by its small population size, no evidence of contact with neighboring populations, and no female immigration. It is believed that most females and adolescent males emigrate from this population. To reveal the genetic signature of these characteristics, we examined the genetic diversity of Bossou and two neighboring populations (Seringbara and Yealé) in the Nimba Mountains by sequencing approximately 605 bp of the mitochondrial DNA (mtDNA) control region. A total of 20 distinct mtDNA variants were observed from 56 sequences of noninvasively collected, anonymous samples. Nucleotide diversity in the Nimba Mountain populations was 0.03-0.04, and did not differ significantly from that in the Bossou population. Very few mitochondrial variants are shared among the sites sampled, which suggests that there is little gene flow involving mtDNA. Nevertheless, no clear population structures were revealed in either population. A comparison with published sequences from West African chimpanzees (Pan troglodytes verus) indicates that the variants observed in the Bossou and Nimba regions are scattered throughout the subspecies, rather than clustered according to geographic region. This suggests that the Bossou-Nimba populations derived only recently from the common ancestral population of the West African chimpanzees, and did not pass through a bottleneck.