Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study.

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303 .

UV RESISTANCE LOCUS 8-Mediated UV-B Response Is Required Alongside CRYPTOCHROME 1 for Plant Survival in Sunlight under Field Conditions.

As sessile, photoautotrophic organisms, plants are subjected to fluctuating sunlight that includes potentially detrimental ultraviolet-B (UV-B) radiation. Experiments under controlled conditions have shown that the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) controls acclimation and tolerance to UV-B in Arabidopsis thaliana; however, its long-term impact on plant fitness under naturally fluctuating environments remain poorly understood. Here, we quantified the survival and reproduction of different Arabidopsis mutant genotypes under diverse field and laboratory conditions. We found that uvr8 mutants produced more fruits than wild type when grown in growth chambers under artificial low-UV-B conditions but not under natural field conditions, indicating a fitness cost in the absence of UV-B stress. Importantly, independent double mutants of UVR8 and the blue light photoreceptor gene CRYPTOCHROME 1 (CRY1) in two genetic backgrounds showed a drastic reduction in fitness in the field. Experiments with UV-B attenuation in the field and with supplemental UV-B in growth chambers demonstrated that UV-B caused the cry1 uvr8 conditional lethal phenotype. Using RNA-seq data of field-grown single and double mutants, we explicitly identified genes showing significant statistical interaction of UVR8 and CRY1 mutations in the presence of UV-B in the field. They were enriched in Gene Ontology categories related to oxidative stress, photoprotection and DNA damage repair in addition to UV-B response. Our study demonstrates the functional importance of the UVR8-mediated response across life stages in natura, which is partially redundant with that of cry1. Moreover, these data provide an integral picture of gene expression associated with plant responses under field conditions.

Comprehensive elucidation of resting-state functional connectivity in anorexia nervosa by a multicenter cross-sectional study.

BACKGROUND: Previous research on the changes in resting-state functional connectivity (rsFC) in anorexia nervosa (AN) has been limited by an insufficient sample size, which reduced the reliability of the results and made it difficult to set the whole brain as regions of interest (ROIs). METHODS: We analyzed functional magnetic resonance imaging data from 114 female AN patients and 135 healthy controls (HC) and obtained self-reported psychological scales, including eating disorder examination questionnaire 6.0. One hundred sixty-four cortical, subcortical, cerebellar, and network parcellation regions were considered as ROIs. We calculated the ROI-to-ROI rsFCs and performed group comparisons. RESULTS: Compared to HC, AN patients showed 12 stronger rsFCs mainly in regions containing dorsolateral prefrontal cortex (DLPFC), and 33 weaker rsFCs primarily in regions containing cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between anterior cingulate cortex (ACC) and thalamus (p < 0.01, false discovery rate [FDR] correction). Comparisons between AN subtypes showed that there were stronger rsFCs between right lingual gyrus and right supracalcarine cortex and between left temporal occipital fusiform cortex and medial part of visual network in the restricting type compared to the binge/purging type (p < 0.01, FDR correction). CONCLUSION: Stronger rsFCs in regions containing mainly DLPFC, and weaker rsFCs in regions containing primarily cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between ACC and thalamus, may represent categorical diagnostic markers discriminating AN patients from HC.

Neighbor GWAS: incorporating neighbor genotypic identity into genome-wide association studies of field herbivory.

An increasing number of field studies have shown that the phenotype of an individual plant depends not only on its genotype but also on those of neighboring plants; however, this fact is not taken into consideration in genome-wide association studies (GWAS). Based on the Ising model of ferromagnetism, we incorporated neighbor genotypic identity into a regression model, named "Neighbor GWAS". Our simulations showed that the effective range of neighbor effects could be estimated using an observed phenotype when the proportion of phenotypic variation explained (PVE) by neighbor effects peaked. The spatial scale of the first nearest neighbors gave the maximum power to detect the causal variants responsible for neighbor effects, unless their effective range was too broad. However, if the effective range of the neighbor effects was broad and minor allele frequencies were low, there was collinearity between the self and neighbor effects. To suppress the false positive detection of neighbor effects, the fixed effect and variance components involved in the neighbor effects should be tested in comparison with a standard GWAS model. We applied neighbor GWAS to field herbivory data from 199 accessions of Arabidopsis thaliana and found that neighbor effects explained 8% more of the PVE of the observed damage than standard GWAS. The neighbor GWAS method provides a novel tool that could facilitate the analysis of complex traits in spatially structured environments and is available as an R package at CRAN ( https://cran.rproject.org/package=rNeighborGWAS ).

Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease.

PURPOSE: Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of the ATP7A gene causes severe neurodegenerative disorders. The present parenteral drugs have limited efficacy, so there is a need for an efficacious drug that can be administered orally. This study focused on glyoxal-bis (N(4)-methylthiosemicarbazonato)-copper(II (CuGTSM), which has shown efficacy in macular mice, a murine model of Menkes disease, and examined its pharmacokinetics. In addition, nanosized CuGTSM (nCuGTSM) was prepared, and the effects of nanosizing on CuGTSM pharmacokinetics were investigated. METHODS: CuGTSM or nCuGTSM (10 mg/kg) was administered orally to male macular mice or C3H/HeNCrl mice (control), and plasma was obtained by serial blood sampling. Plasma concentrations of CuGTSM and GTSM were measured by LC-MS/MS and pharmacokinetic parameters were calculated. RESULTS: When CuGTSM was administered orally, CuGTSM and GTSM were both detected in the plasma of both mouse strains. When nCuGTSM was administered, the Cmax was markedly higher, and the mean residence time was longer than when CuGTSM was administered for both CuGTSM and GTSM in both mouse strains. With macular mice, the AUC ratio (GTSM/CuGTSM) was markedly higher and the plasma CuGTSM concentration was lower than with C3H/HeNCrl mice when either CuGTSM or nCuGTSM was administered. CONCLUSION: Absorption of orally administered CuGTSM was confirmed in macular mice, and the nano-formulation improved the absorption and retention of CuGTSM in the body. However, the plasma concentration of CuGTSM was lower in macular mice than in control mice, suggesting easier dissociation of CuGTSM.

Trace element levels in mature breast milk of recently lactating Japanese women.

BACKGROUND: Many trace elements are essential for infant growth and development during early life. Their concentrations in breast milk vary depending on social and economic factors. Nonetheless, the present available values in Japan were derived from lactating mothers approximately 15 years ago. METHODS: Healthy mothers who gave birth to a single infant after 37 weeks of gestation at Teikyo University Hospital were recruited between July 2016 and December 2017. They were encouraged to collect breast milk samples and a self-administered food frequency questionnaire at 1 and 3 months postpartum. Anthropometric data for the mothers and their infants were also collected. Overall, 79 subjects were analyzed after excluding subjects with inadequate data in the food frequency questionnaire, insufficient breast milk samples, and medication that could affect dietary intakes. Trace element concentrations were determined by inductively coupled plasma mass spectrometry, and their correlation with several factors were investigated. RESULTS: Trace element concentrations were widely distributed as previously reported. Median concentrations of Cr, Mn, Fe, Cu, Zn, Se, and Mo were 0.8, 0.8, 98, 50, 272, 2.2, and 0.7 µg/dL at 1 month postpartum and 0.6, 0.7, 55, 33, 177, 2.1, and 0.7 µg/dL at 3 months postpartum, respectively. There were no correlations between trace element concentrations and either mothers' intakes or infants' growth. In contrast, there were significant correlations between several trace elements and macronutrients in addition to inter-element correlations among almost all trace elements. CONCLUSIONS: Trace element concentrations in mature breast milk were determined from recently lactating mothers in Japan.

New Bifunctional Bis(azairidacycle) with Axial Chirality via Double Cyclometalation of 2,2'-Bis(aminomethyl)-1,1'-binaphthyl.

As a candidate for bifunctional asymmetric catalysts containing a half-sandwich C-N chelating Ir(III) framework (azairidacycle), a dinuclear Ir complex with an axially chiral linkage is newly designed. An expedient synthesis of chiral 2,2'-bis(aminomethyl)-1,1'-binaphthyl (1) from 1,1-bi-2-naphthol (BINOL) was accomplished by a three-step process involving nickel-catalyzed cyanation and subsequent reduction with Raney-Ni and KBH4. The reaction of (S)-1 with an equimolar amount of [IrCl2Cp*]2 (Cp* = η5-C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 °C gave a diastereomeric mixture of new dinuclear dichloridodiiridium complexes (5) through the double C-H bond cleavage, as confirmed by 1H NMR spectroscopy. A loss of the central chirality on the Ir centers of 5 was demonstrated by treatment with KOC(CH3)3 to generate the corresponding 16e amidoiridium complex 6. The following hydrogen transfer from 2-propanol to 6 provided diastereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%.

Plant trichomes and a single gene GLABRA1 contribute to insect community composition on field-grown Arabidopsis thaliana.

BACKGROUND: Genetic variation in plants alters insect abundance and community structure in the field; however, little is known about the importance of a single gene among diverse plant genotypes. In this context, Arabidopsis trichomes provide an excellent system to discern the roles of natural variation and a key gene, GLABRA1, in shaping insect communities. In this study, we transplanted two independent glabrous mutants (gl1-1 and gl1-2) and 17 natural accessions of Arabidopsis thaliana to two localities in Switzerland and Japan. RESULTS: Fifteen insect species inhabited the plant accessions, with the insect community composition significantly attributed to variations among plant accessions. The total abundance of leaf-chewing herbivores was negatively correlated with trichome density at both field sites, while glucosinolates had variable effects on leaf chewers between the sites. Interestingly, there was a parallel tendency for the abundance of leaf chewers to be higher on gl1-1 and gl1-2 than on their different parental accessions, Ler-1 and Col-0, respectively. Furthermore, the loss of function in the GLABRA1 gene significantly decreased the resistance of plants to the two predominant chewers; flea beetles and turnip sawflies. CONCLUSIONS: Overall, our results indicate that insect community composition significantly varies among A. thaliana accessions across two distant field sites, with GLABRA1 playing a key role in altering the abundance of leaf-chewing herbivores. Given that such a trichome variation is widely observed in Brassicaceae plants, the present study exemplifies the community-wide effect of a single plant gene on crucifer-feeding insects in the field.

Geographical co-occurrence of butterfly species: the importance of niche filtering by host plant species.

The relevance of interspecific resource competition in the context of community assembly by herbivorous insects is a well-known topic in ecology. Most previous studies focused on local species assemblies that shared host plants. Few studies evaluated species pairs within a single taxon when investigating the effects of host plant sharing at the regional scale. Herein, we explore the effect of plant sharing on the geographical co-occurrence patterns of 232 butterflies distributed across the Japanese archipelago; we use two spatial scales (10 × 10 and 1 × 1 km grids) to this end. We considered that we might encounter one of two predictable patterns in terms of the relationship between co-occurrence and host sharing among butterflies. On the one hand, host sharing might promote distributional exclusivity attributable to interspecific resource competition. On the other hand, sharing of host plants may promote co-occurrence attributable to filtering by resource niche. At both grid scales, we found significant negative correlations between host use similarity and distributional exclusivity. Our results support the hypothesis that the butterfly co-occurrence pattern across the Japanese archipelago is better explained by filtering via resource niche rather than interspecific resource competition.

Herbivore-Mediated Interaction Promotes the Maintenance of Trichome Dimorphism through Negative Frequency-Dependent Selection.

Natural plant populations exhibit genetic variation in defense traits against herbivores. Despite a growing body of evidence for herbivore-mediated selection on plant defenses, we still know little about how genetic variation persists in antiherbivore defense traits. Here we present field and experimental evidence for herbivore-mediated frequency-dependent selection that promotes the maintenance of trichome-producing (hairy) and trichomeless (glabrous) plants of Arabidopsis halleri subsp. gemmifera. First, in a natural population where the specialist leaf beetle Phaedon brassicae was prevalent, hairy plants were damaged less when the frequency of neighboring glabrous plants increased. Furthermore, temporal variation in the frequency of the two plant morphs showed that rarer morphs increased in frequency at the scale of 1-m-diameter patches between survey years. Using a mesocosm experiment, we demonstrated a rare-morph advantage for defense (leaf damage and herbivore abundance) and reproduction (flower and clone production) between hairy and glabrous plants in the presence of P. brassicae. However, this rare-morph advantage was not detected when beetles were absent, with glabrous plants having higher reproduction than hairy plants under these conditions regardless of frequency conditions. These findings highlight the overlooked but potentially critical role of herbivore-mediated apparent interaction in maintaining plant defense polymorphism.

Novel Mapping Technique for Localization of Focal and Reentrant Activation During Atrial Fibrillation.

INTRODUCTION: Identification of wavefront propagation pattern during AF remains challenging in ablation procedures. We sought to test a novel combination of a new mapping technology called Ripple Map and high-density mapping to distinguish focal and reentrant activation during atrial fibrillation (AF). METHODS AND RESULTS: Subjects were patients undergoing ablation for persistent AF. If AF remained after isolation of the pulmonary veins, the left atrium (LA) was mapped by a high-density mapping catheter for later analysis, after which ablation was continued using a conventional stepwise approach. After the procedure, electrograms from the high-density mapping catheter were analyzed using Ripple Map, which is a new feature in the CARTO®3, and type of activation on ≥3 consecutive AF cycles was determined. High-density mapping was performed on 569 sites in 45 patients (13 ± 3 sites per patient). AF wavefront propagation determined by Ripple Map was in good agreement with analysis of manual annotation of bipolar electrograms. Ripple Map's representation of wavefront activation pattern, which could include local as well as far-field activity, allowed us to identify focal activation in 64 (11%) sites and 1 (0.2%) reentrant activation site. Radiofrequency delivery in atrial regions with activation sites identified as focal by Ripple Map resulted in termination of AF more often than regions without focal activation (22% vs. 7%, P = 0.015). CONCLUSION: This study demonstrated that Ripple Map enabled quick identification of AF wavefront activation pattern, potentially being helpful for determining ablation targets in persistent AF.

Occurrence of Focal Atrial Tachycardia During the Ablation Procedure Is Associated With Arrhythmia Recurrence After Termination of Persistent Atrial Fibrillation.

INTRODUCTION: Catheter ablation can terminate persistent atrial fibrillation (AF). However, atrial tachycardia (AT) often arises after termination of AF. METHODS AND RESULTS: Of 215 patients who underwent index stepwise ablation for persistent AF, 141 (66%) patients (64 ± 9 years) in whom AF terminated during the ablation procedure were studied. If AF converted into AT, ablation for AT was subsequently performed. ATs were categorized as focal or macroreentrant AT. We assessed whether type of AT occurring after conversion of AF during the ablation procedure was associated with freedom from atrial tachyarrhythmia (AF or AT) during follow-up. Sinus rhythm was directly restored from AF in 37 patients, while 34, 37, and 33 patients had focal AT alone, a mix of focal and macroreentrant AT, and macroreentrant AT alone after termination of AF, respectively. Arrhythmia-free survival rates at 1 year after the index procedure were 30%, 34%, 61%, and 59% in the patients with focal AT alone, a mix of focal AT and macroreentrant AT, macroreentrant AT alone, and direct restoration of sinus rhythm, respectively (P = 0.004). Type of AT occurring during the index procedure was associated with type of recurrent AT (P = 0.03), but the origin of focal AT occurring during the index ablation differed from that of the recurrent AT in 85% of patients. CONCLUSION: In patients who had AF termination by ablation, occurrence of focal AT during the ablation procedure was associated with worse clinical outcome than occurrence of macroreentrant AT, likely due to ATs arising from other foci during follow-up.

Low serum biotin in Japanese children fed with hydrolysate formula.

BACKGROUND: Given that nutritional biotin deficiency in Japanese infants has been reported, a straightforward method for estimating biotin level is needed. The biotin content in infant formula, breast milk, and the sera of infants fed with various types of formula were measured using avidin-binding assay. METHODS: A commercially available ELISA kit was used for the measurement of biotin in 54 types of formula, including hydrolysate formulas for milk allergy, as well as in breast milk and in the sera of 27 infants fed with these formulas. RESULTS: The biotin content reached the recommended value in only five formulas. All of the hydrolysate formulas and more than half of the special formulas contained biotin <0.1 µg/dL. Serum biotin was low in infants fed only with the hydrolysate formulas, and one of them had alopecia related to biotin deficiency. CONCLUSION: While many were asymptomatic, infants fed with formulas lacking biotin are at risk of developing symptomatic disease. The addition of biotin to breast milk substitutes was finally approved in the middle of 2014, however pediatricians in Japan should still be vigilant with regard to nutritional biotin deficiency in infants for the time being.

Serum biotin in Japanese children: Enzyme-linked immunosorbent assay measurement.

BACKGROUND: Biotin deficiency has been reported in Japanese infants fed special formulas for medical reasons, including those with milk allergy and congenital metabolic diseases, because these formulas contain little biotin. Serum biotin measurement is useful for diagnosing biotin deficiency. We applied a simple and rapid method to analyze serum biotin, and established normal ranges for children and adults. METHODS: Serum biotin in 188 healthy Japanese children aged 0-4 years and in 25 healthy adults was analyzed using a Biotin ELISA Kit (immundiagnostik). The effects of various conditions on the measurement of serum biotin were also examined. RESULTS: Median biotin in children aged 0-4 years was 10.4 ng/dL (IQR, 7.9-13.4 ng/dL), and that in adults was 12.9 ng/dL (IQR, 10.8-15.8 ng/dL). Normal range was 4.7-22.0 ng/dL in children and 8.4-20.5 ng/dL in adults (calculated using two-sided 95%CI). Measurements obtained with this method were not affected by frozen storage, freeze-thaw, or hemolysis, indicating that serum biotin can be analyzed accurately under these conditions, with a possible application to plasma samples. CONCLUSIONS: Serum biotin was significantly lower in children than in adults, with the normal range being 4.7-22.0 ng/dL in children and 8.4-20.5 ng/dL in adults. This simple and accurate enzyme-linked immunosorbent assay method is useful for diagnosing biotin deficiency.

Delayed increase in male suicide rates in tsunami disaster-stricken areas following the great east japan earthquake: a three-year follow-up study in Miyagi Prefecture.

Devastating natural disasters and their aftermath are known to cause psychological distress. However, little information is available regarding suicide rates following tsunami disasters that destroy regional social services and networks. The aim of the present study was to determine whether the tsunami disaster following the Great East Japan Earthquake in March 2011 has influenced suicide rates. The study period was from March 2009 to February 2014. Tsunami disaster-stricken areas were defined as the 16 municipalities facing the Pacific Ocean in Miyagi Prefecture. Inland areas were defined as other municipalities in Miyagi that were damaged by the earthquake. Suicide rates in the tsunami disaster-stricken areas were compared to national averages, using a time-series analysis and the Poisson distribution test. In tsunami disaster-stricken areas, male suicide rates were significantly lower than the national average during the initial post-disaster period and began to increase after two years. Likewise, male suicide rates in the inland areas decreased for seven months, and then increased to exceed the national average. In contrast, female post-disaster suicide rates did not change in both areas compared to the national average. Importantly, the male suicide rates in the inland areas started to increase earlier compared to the tsunami-stricken areas, which may reflect the relative deficiency of mental healthcare services in the inland areas. Considering the present status that many survivors from the tsunami disaster still live in temporary housing and face various challenges to rebuild their lives, we should continue intensive, long-term mental healthcare services in the tsunami-stricken areas.

Altered cognitive function of prefrontal cortex during error feedback in patients with irritable bowel syndrome, based on FMRI and dynamic causal modeling.

BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) have increased activity in the insula and reduced activation of the dorsolateral prefrontal cortex (DLPFC) in response to visceral stimulation. We investigated whether they have latent impairments in cognitive flexibility because of dysfunction in the DLPFC and insula and altered connectivity between brain regions. METHODS: We analyzed data from 30 individuals with IBS (15 men; age, 21.7 ± 3.0 y) diagnosed based on Rome III criteria, along with 30 individuals matched for age, sex, and education level (controls). Event-related functional magnetic resonance imaging of the brain was performed to evaluate cognitive flexibility and was assessed by the Wisconsin Card Sorting Test, in which subjects are allowed to change choice criteria, defined as set-shifting in response to error feedback. Brain images were analyzed with statistical parametric mapping 5 and 8 software and dynamic causal modeling. RESULTS: Subjects with IBS had significantly more Nelson perseverative errors (P < .05) and set-maintenance difficulties (P < .05) than controls. They also showed significantly decreased activity of the right DLPFC (Brodmann's area 9; P < .001) and right hippocampus (P < .001), and significantly increased activity of the left posterior insula (P < .001) at error feedback during set-shifting. Dynamic causal modeling analysis during set-shifting revealed significantly less connectivity from the DLPFC to pre-supplementary motor area in subjects with IBS, compared with controls (P = .012). CONCLUSIONS: Individuals with IBS have latent impairments in cognitive flexibility as a result of altered activity of the DLPFC, insula, and hippocampus, and impaired connectivity between the DLPFC and pre-supplementary motor area.

Detecting frequency-dependent selection through the effects of genotype similarity on fitness components.

Frequency-dependent selection (FDS) is an evolutionary regime that can maintain or reduce polymorphisms. Despite the increasing availability of polymorphism data, few effective methods are available for estimating the gradient of FDS from the observed fitness components. We modeled the effects of genotype similarity on individual fitness to develop a selection gradient analysis of FDS. This modeling enabled us to estimate FDS by regressing fitness components on the genotype similarity among individuals. We detected known negative FDS on the visible polymorphism in a wild Arabidopsis and damselfly by applying this analysis to single-locus data. Further, we simulated genome-wide polymorphisms and fitness components to modify the single-locus analysis as a genome-wide association study (GWAS). The simulation showed that negative or positive FDS could be distinguished through the estimated effects of genotype similarity on simulated fitness. Moreover, we conducted the GWAS of the reproductive branch number in Arabidopsis thaliana and found that negative FDS was enriched among the top-associated polymorphisms of FDS. These results showed the potential applicability of the proposed method for FDS on both visible polymorphism and genome-wide polymorphisms. Overall, our study provides an effective method for selection gradient analysis to understand the maintenance or loss of polymorphism.

Genome-wide association study of aphid abundance highlights a locus affecting plant growth and flowering in Arabidopsis thaliana.

Plant life-history traits, such as size and flowering, contribute to shaping variation in herbivore abundance. Although plant genes involved in physical and chemical traits have been well studied, less is known about the loci linking plant life-history traits and herbivore abundance. Here, we conducted a genome-wide association study (GWAS) of aphid abundance in a field population of Arabidopsis thaliana. This GWAS of aphid abundance detected a relatively rare but significant variant on the third chromosome of A. thaliana, which was also suggestively but non-significantly associated with the presence or absence of inflorescence. Out of candidate genes near this significant variant, a mutant of a ribosomal gene (AT3G13882) exhibited slower growth and later flowering than a wild type under laboratory conditions. A no-choice assay with the turnip aphid, Lipaphis erysimi, found that aphids were unable to successfully establish on the mutant. Our GWAS of aphid abundance unexpectedly found a locus affecting plant growth and flowering.

Guided Internet-Based Cognitive Behavioral Therapy for Women With Bulimia Nervosa: Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Individual face-to-face cognitive behavioral therapy is known to be effective for bulimia nervosa (BN). Since foods vary considerably between regions and cultures in which patients live, cultural adaptation of the treatment program is particularly important in cognitive behavioral therapy for BN. Recently, an internet-based cognitive behavioral therapy (ICBT) program was developed for Japanese women with BN, adapted to the Japanese food culture. However, no previous randomized controlled trial has examined the effectiveness of ICBT. OBJECTIVE: This paper presents a research protocol for strategies to examine the effects of guided ICBT. METHODS: This study is designed as a multicenter, prospective, assessor-blinded randomized controlled trial. The treatment groups will be divided into treatment as usual (TAU) alone as the control group and ICBT combined with TAU as the intervention group. The primary outcome is the total of binge eating and purging behaviors assessed before and after treatment by an independent assessor. Secondary outcomes will include measures of eating disorder severity, depression, anxiety, quality of life, treatment satisfaction, and working alliances. Treatment satisfaction and working alliances will be measured post assessment only. Other measures will be assessed at baseline, post intervention, and follow-up, and the outcomes will be analyzed on an intention-to-treat basis. RESULTS: This study will be conducted at 7 different medical institutions in Japan from August 2022 to October 2026. Recruitment of participants began on August 19, 2022, and recruitment is scheduled to continue until July 2024. The first participants were registered on September 8, 2022. CONCLUSIONS: This is the first multicenter randomized controlled trial in Japan comparing the effectiveness of ICBT and TAU in patients with BN. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000048732; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055522. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49828.

Economic costs for outpatient treatment of eating disorders in Japan.

BACKGROUND: Few studies have examined the economic costs of outpatient care for eating disorders in Japan. This study aimed to clarify the reimbursement for outpatient treatment of eating disorders and compare the costs between the departments of Psychosomatic Medicine and Psychiatry in Japan. METHOD: A multicenter, prospective, observational study of patients with an eating disorder was conducted in the Psychosomatic Medicine departments of three centers and the Psychiatry departments of another three centers in Japan. We analyzed medical reimbursement for an outpatient revisit, time of clinical interviews, and the treatment outcome measured by the Eating Disorder Examination Questionnaire (EDE-Q) global scores and body mass index (BMI) at 3 months. Multivariate linear regression models were performed to adjust for covariates. RESULTS: This study included 188 patients in the Psychosomatic Medicine departments and 68 in the Psychiatry departments. The average reimbursement cost for an outpatient revisit was 4670 yen. Even after controlling for covariates, the Psychosomatic Medicine departments had lower reimbursement points per minute of interviews than the Psychiatry departments (coefficient = - 23.86; 95% confidence interval = - 32.09 to - 15.63; P < 0.001). In contrast, EDE-Q global scores and BMI at 3 months were not significantly different between these departments. CONCLUSIONS: This study clarifies the economic costs of treating outpatients with eating disorders in Japan. The medical reimbursement points per interview minute were lower in Psychosomatic Medicine departments than in Psychiatry departments, while there were no apparent differences in the treatment outcomes. Addressing this issue is necessary to provide an adequate healthcare system for patients with eating disorders in Japan.

This study examined the cost of outpatient care for eating disorders in Japan, comparing treatment costs between the Psychosomatic Medicine and Psychiatry departments. The actual cost of outpatient care for eating disorders in Japan was clarified. The results indicate that Psychosomatic Medicine departments have lower reimbursement points per interview time compared to the Psychiatry departments, but there were no noticeable differences in treatment outcomes between the two. This highlights the need to address this cost difference to improve the healthcare system for patients with eating disorders in Japan.