The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Crystal structures of photosystem II from a cyanobacterium expressing psbA2 in comparison to psbA3 reveal differences in the D1 subunit.

Three psbA genes (psbA1, psbA2, and psbA3) encoding the D1 subunit of photosystem II (PSII) are present in the thermophilic cyanobacterium Thermosynechococcus elongatus and are expressed differently in response to changes in the growth environment. To clarify the functional differences of the D1 protein expressed from these psbA genes, PSII dimers from two strains, each expressing only one psbA gene (psbA2 or psbA3), were crystallized, and we analyzed their structures at resolutions comparable to previously studied PsbA1-PSII. Our results showed that the hydrogen bond between pheophytin/D1 (PheoD1) and D1-130 became stronger in PsbA2- and PsbA3-PSII due to change of Gln to Glu, which partially explains the increase in the redox potential of PheoD1 observed in PsbA3. In PsbA2, one hydrogen bond was lost in PheoD1 due to the change of D1-Y147F, which may explain the decrease in stability of PheoD1 in PsbA2. Two water molecules in the Cl-1 channel were lost in PsbA2 due to the change of D1-P173M, leading to the narrowing of the channel, which may explain the lower efficiency of the S-state transition beyond S2 in PsbA2-PSII. In PsbA3-PSII, a hydrogen bond between D1-Ser270 and a sulfoquinovosyl-diacylglycerol molecule near QB disappeared due to the change of D1-Ser270 in PsbA1 and PsbA2 to D1-Ala270. This may result in an easier exchange of bound QB with free plastoquinone, hence an enhancement of oxygen evolution in PsbA3-PSII due to its high QB exchange efficiency. These results provide a structural basis for further functional examination of the three PsbA variants.

Cognitive behavior therapy for autistic adolescents, awareness and care for my autistic traits program: a multicenter randomized controlled trial.

BACKGROUND: Autistic people demonstrate focused interests, sensitivity to sensory stimulation, and, compared with the general population, differences in social communication and interaction. We examined whether a combination of the Awareness and Care for My Autistic Traits (ACAT) program and treatment-as-usual is more effective than only treatment-as-usual in increasing the understanding of autistic attributes, reducing treatment stigma, and improving mental health and social adaptation among autistic adolescents and their parents/guardians. METHODS: Forty-nine adolescents and their parents/guardians were randomly assigned to either a combination of ACAT and treatment-as-usual or only treatment-as-usual. The combined group received six weekly 100-minute ACAT sessions, while the treatment-as-usual group received no additional intervention. The primary outcome was the change in understanding of autistic attributes (Autism Knowledge Quiz-Child), administered from pre- to post-intervention. The secondary outcomes included the change in Autism Knowledge Quiz-Parent, reduced treatment stigma, and improved mental health and social adaptation among autistic adolescents and their parents/guardians. A primary outcome measure scale was scored by assessors who were blind to the group assignment. RESULTS: The combined group (both autistic adolescents and their parents/guardians) showed an increase in Autism Knowledge Quiz scores compared to those in the treatment-as-usual group. Autistic adolescents in the combined group also demonstrated a decrease in treatment-related stigma and an improvement in general mental health compared to those in the treatment-as-usual group, while there were no group differences in the change in social adaptation. For parents/guardians, there were no group differences in the change in treatment-related stigma, general mental health, adaptive skills, or attitudes toward their children. CONCLUSIONS: The ACAT program could be an effective treatment modality to increase the understanding of autistic attributes among both autistic adolescents and their parents/guardians. The ACAT program positively affects self-understanding, reduces treatment stigma, and stabilizes behavioral issues for autistic adolescents as a part of mental health measures, but it does not effectively reduce treatment barriers or improve mental health for parents/guardians. Further research should consider whether additional support for parents/guardians could be beneficial. TRIAL REGISTRATION: The study was registered in UMIN (UMIN000029851, 06/01/2018).

[Exploratory Study of the Risk Factors for Acute Kidney Injury in the Cisplatin Combination Chemotherapy for Solid Cancer].

In the present study, we investigated the rate of cisplatin(CDDP)-induced acute kidney injury(CIA)and examined its association with various clinical factors in the combination therapy with CDDP for solid cancers. A total of 726 cases of solid cancer that had been indicated for the CDDP combination regimen from December 2012 to December 2013 were enrolled. CIA occurred in 48 cases(6.6%). The multivariate analysis revealed that diabetes, the regular use of non-steroidal anti- inflammatory drugs(NSAIDs), first dose of CDDP, and severe hyponatremia(≥Grade 3)within one week after CDDP administration were significantly associated with an increased risk for CIA, whereas magnesium supplementation was associated with a significantly reduced risk for CIA. Particularly, diabetes and cardiovascular disease were identified as risk factors for CIA in patients with esophageal and head and neck cancers. Based on the results of this survey, it is important to formulate preventive measures, evaluate risk factors, and respond rapidly.

Crystal structure and redox properties of a novel cyanobacterial heme protein with a His/Cys heme axial ligation and a Per-Arnt-Sim (PAS)-like domain.

Photosystem II catalyzes light-induced water oxidation leading to the generation of dioxygen indispensable for sustaining aerobic life on Earth. The Photosystem II reaction center is composed of D1 and D2 proteins encoded by psbA and psbD genes, respectively. In cyanobacteria, different psbA genes are present in the genome. The thermophilic cyanobacterium Thermosynechococcus elongatus contains three psbA genes: psbA1, psbA2, and psbA3, and a new c-type heme protein, Tll0287, was found to be expressed in a strain expressing the psbA2 gene only, but the structure and function of Tll0287 are unknown. Here we solved the crystal structure of Tll0287 at a 2.0 Å resolution. The overall structure of Tll0287 was found to be similar to some kinases and sensor proteins with a Per-Arnt-Sim-like domain rather than to other c-type cytochromes. The fifth and sixth axial ligands for the heme were Cys and His, instead of the His/Met or His/His ligand pairs observed for most of the c-type hemes. The redox potential, E½, of Tll0287 was -255 ± 20 mV versus normal hydrogen electrode at pH values above 7.5. Below this pH value, the E½ increased by ≈57 mV/pH unit at 15 °C, suggesting the involvement of a protonatable group with a pKred = 7.2 ± 0.3. Possible functions of Tll0287 as a redox sensor under microaerobic conditions or a cytochrome subunit of an H2S-oxidizing system are discussed in view of the environmental conditions in which psbA2 is expressed, as well as phylogenetic analysis, structural, and sequence homologies.

Internet-Based Cognitive Behavioral Therapy With Real-Time Therapist Support via Videoconference for Patients With Obsessive-Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Pilot Single-Arm Trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. OBJECTIVES: This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD. METHODS: A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants' points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment. RESULTS: A significant reduction in symptom of obsession-compulsion (Y-BOCS=-6.2; Cohen d=0.74; 95% CI -9.4 to -3.0, P=.002), panic (PDSS=-5.6; Cohen d=0.89; 95% CI -9.83 to -1.37; P=.02), social anxiety (LSAS=-33.6; Cohen d=1.10; 95% CI -59.62 to -7.49, P=.02) were observed. In addition, depression (PHQ-9=-1.72; Cohen d=0.27; 95% CI -3.26 to -0.19; P=.03) and general anxiety (GAD-7=-3.03; Cohen d=0.61; 95% CI -4.57 to -1.49, P<.001) were significantly improved. Although there were no significant changes at 16 weeks from baseline in EQ-5D (0.0336; Cohen d=-0.202; 95% CI -0.0198 to 0.00869; P=.21), there were high therapeutic alliance (ie, WAI-SF) scores (from 68.0 to 73.7) throughout treatment, which significantly increased (4.14; 95% CI 1.24 to 7.04; P=.007). Of the participants, 86% (25/29) were satisfied with videoconference-delivered CBT, and 83% (24/29) preferred videoconference-delivered CBT to face-to-face CBT. An adverse event occurred to a patient with SAD; the incidence was 3% (1/30). CONCLUSIONS: Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable.

Relationship between symptom dimensions and white matter alterations in obsessive-compulsive disorder.

OBJECTIVE: To investigate the relationship between the severities of symptom dimensions in obsessive-compulsive disorder (OCD) and white matter alterations. METHODS: We applied tract-based spatial statistics for diffusion tensor imaging (DTI) acquired by 3T magnetic resonance imaging. First, we compared fractional anisotropy (FA) between 20 OCD patients and 30 healthy controls (HC). Then, applying whole brain analysis, we searched the brain regions showing correlations between the severities of symptom dimensions assessed by Obsessive-Compulsive Inventory-Revised and FA in all participants. Finally, we calculated the correlations between the six symptom dimensions and multiple DTI measures [FA, axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD)] in a region-of-interest (ROI) analysis and explored the differences between OCD patients and HC. RESULTS: There were no between-group differences in FA or brain region correlations between the severities of symptom dimensions and FA in any of the participants. ROI analysis revealed negative correlations between checking severity and left inferior frontal gyrus white matter and left middle temporal gyrus white matter and a positive correlation between ordering severity and right precuneus in FA in OCD compared with HC. We also found negative correlations between ordering severity and right precuneus in RD, between obsessing severities and right supramarginal gyrus in AD and MD, and between hoarding severity and right insular gyrus in AD. CONCLUSION: Our study supported the hypothesis that the severities of respective symptom dimensions are associated with different patterns of white matter alterations.

Cognitive Behavioral Therapy for Patients with Social Anxiety Disorder Who Remain Symptomatic following Antidepressant Treatment: A Randomized, Assessor-Blinded, Controlled Trial.

BACKGROUND: Although antidepressants are still a commonly used treatment for social anxiety disorder (SAD), a significant proportion of patients fail to remit following antidepressants. However, no standard approach has been established for managing such patients. This study aimed to examine the effectiveness of cognitive behavioral therapy (CBT) as an adjunct to usual care (UC) compared with UC alone in SAD patients who remain symptomatic following antidepressant treatment. METHODS: This was a prospective randomized open-blinded end-point study with two parallel groups (CBT + UC, and UC alone, both for 16 weeks) conducted from June 2012 to March 2014. SAD patients who remain symptomatic following antidepressant treatment were recruited, and a total sample size of 42 was set based on pilot results. RESULTS: Patients were randomly allocated to CBT + UC (n = 21) or UC alone (n = 21). After 16 weeks, adjusted mean reduction in the Liebowitz Social Anxiety Scale from baseline for CBT + UC and UC alone was -40.87 and 0.68, respectively; the between-group difference was -41.55 (-53.68 to -29.42, p < 0.0001). Response rates were 85.7 and 10.0% for CBT + UC and UC alone, respectively (p < 0.0001). The corresponding remission rates were 47.6 and 0.0%, respectively (p = 0.0005). Significant differences were also found in favor of CBT + UC for social anxiety symptoms, depressive symptoms, and functional impairment. CONCLUSIONS: Our results suggest that in SAD patients who have been ineffectively treated with antidepressants, CBT is an effective treatment adjunct to UC over 16 weeks in reducing social anxiety and related symptoms.

Acute pulmonary hypertension due to microthrombus formation following COVID-19 vaccination: a case report.

Background: Several side effects have been reported after mRNA COVID-19 vaccinations. Nonetheless, the risk of pulmonary hypertension (PH) is rarely reported. Most cases with acute PH following vaccination were due to macropulmonary embolism secondary to deep vein thrombosis. However, acute PH due to microthrombus formation after COVID-19 vaccination has not been reported before, although a microthrombus has been considered to lead to the dysfunction of multiple organs, particularly in patients infected with COVID-19. Case summary: A 63-year-old woman without any past medical history presented to our hospital with facial and bilateral pedal oedema and progressive dyspnoea on exertion. Her symptoms began the day after her second COVID-19 vaccination and developed gradually, which prompted her to seek consultation in our hospital 6 weeks later. An echocardiogram revealed substantially elevated right heart pressure, and cardiac catheterization revealed high pulmonary artery pressure (mean PAP, 30 mmHg). Contrast-enhanced computed tomography and venous echography revealed no apparent thrombus, and ventilation/perfusion (V/Q) scintigraphy revealed no V/Q mismatch. However, elevated D-dimer indicated the presence of a coagulation-fibrinolysis system in her body; thus, heparin therapy was initiated intravenously on Day 3 for 4 days, followed by direct oral anticoagulants ended on Day 16. Her symptoms substantially improved as her D-dimer level decreased, and a follow-up cardiac catheterization on Day 14 revealed a decline in mean PAP (15 mmHg). Discussion: Our case suggests that the presence of acute PH is likely due to microangiopathy. Further studies are required to reveal the relationship between immune responses and microthrombus formation after COVID-19 vaccination.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Current status of research on cognitive therapy/cognitive behavior therapy in Japan.

Cognitive therapy/cognitive behavior therapy was introduced into the field of psychiatry in the late 1980s in Japan, and the Japanese Association for Cognitive Therapy (JACT), founded in 2004, now has more than 1500 members. Along with such progress, awareness of the effectiveness of cognitive therapy/cognitive behavioral therapy has spread, not only among professionals and academics but also to the public. The Study Group of the Procedures and Effectiveness of Psychotherapy, funded by the Ministry of Health, Labor and Welfare, has conducted a series of studies on the effectiveness of cognitive therapy/cognitive behavior therapy since 2006 and shown that it is feasible for Japanese patients. As a result, in April 2010 cognitive therapy/cognitive behavior therapy for mood disorders was added to the national health insurance scheme in Japan. This marked a milestone in Japan's psychiatric care, where pharmacotherapy has historically been more common. In this article the authors review research on cognitive therapy/cognitive behavior therapy in Japan.

Associations between autism spectrum disorder and eating disorders with and without self-induced vomiting: an empirical study.

BACKGROUND: Although approximately 23% of anorexia nervosa (AN) patients have concomitant autism spectrum disorder (ASD), it is clinically difficult to determine ASD coexistence in patients with eating disorders. Restrictive AN is more common in younger patients and self-induced vomiting usually appears during adolescence/young adulthood, in order to prevent gaining weight caused by overeating. However, some patients are tolerant of weight gain even if they start overeating. It is important to understand the essential difference between those who vomit and those who do not vomit. In this study, we hypothesised that the absence of self-induced vomiting may be associated with the presence of ASD and aimed to assess the presence of ASD traits in each eating disorder (EDs). Clarifying this association helps to consider the coexistence of ASD in the clinical setting and can lead to the next detailed ASD evaluation, and as a result, helps to determine the appropriate treatment and support individually. METHODS: We retrospectively evaluated 43 females aged 15-45 years who attended Chiba University Hospital between 2012 and 2016 using the Eating Disorder Examination Questionnaire (EDE-Q) and Autism-Spectrum Quotient (AQ) to quantify the severity of the EDs and to identify whether ASD traits were present. RESULTS: There was no difference in the AQ score between bingeing-purging type AN and restricting type AN. However, there was significant difference in the AQ score between bulimia nervosa and binge EDs (BED). Of the 4 ED subtypes, BED had the highest ASD traits. The non-vomiting group with illness duration < 4 years had a significantly higher AQ communication score than the vomiting group with illness duration ≥4 years. CONCLUSIONS: There was a difference in the AQ score by the presence or absence of self-induced vomiting. The results of this study suggest an association between high scores on AQ and non-vomiting. Thus, evaluation of patients for the absence of self-induced vomiting while assessing them for EDs may help us to understand the association with ASD traits.

Decomposing normal and abnormal features of medical images for content-based image retrieval of glioma imaging.

In medical imaging, the characteristics purely derived from a disease should reflect the extent to which abnormal findings deviate from the normal features. Indeed, physicians often need corresponding images without abnormal findings of interest or, conversely, images that contain similar abnormal findings regardless of normal anatomical context. This is called comparative diagnostic reading of medical images, which is essential for a correct diagnosis. To support comparative diagnostic reading, content-based image retrieval (CBIR) that can selectively utilize normal and abnormal features in medical images as two separable semantic components will be useful. In this study, we propose a neural network architecture to decompose the semantic components of medical images into two latent codes: normal anatomy code and abnormal anatomy code. The normal anatomy code represents counterfactual normal anatomies that should have existed if the sample is healthy, whereas the abnormal anatomy code attributes to abnormal changes that reflect deviation from the normal baseline. By calculating the similarity based on either normal or abnormal anatomy codes or the combination of the two codes, our algorithm can retrieve images according to the selected semantic component from a dataset consisting of brain magnetic resonance images of gliomas. Moreover, it can utilize a synthetic query vector combining normal and abnormal anatomy codes from two different query images. To evaluate whether the retrieved images are acquired according to the targeted semantic component, the overlap of the ground-truth labels is calculated as metrics of the semantic consistency. Our algorithm provides a flexible CBIR framework by handling the decomposed features with qualitatively and quantitatively remarkable results.

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Regional gray and white matter volume abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study.

Previous studies have demonstrated both functional and structural abnormalities in the frontal-striatal-thalamic circuits in obsessive-compulsive disorder (OCD). The purpose of this study was to assess volume abnormalities not only of gray matter (GM), but also of white matter (WM) in patients with OCD using voxel-based morphometry (VBM). Subjects consisted of 23 patients with OCD and 26 normal control subjects. All patients were drug-free for at least 2 weeks before the study. Three-dimensional T1-weighed MR images were obtained in all subjects. Optimized voxel-based morphometry was performed to detect structural difference between the two groups. The patients with OCD demonstrated a significant reduction of GM volume in the bilateral medial prefrontal cortex, right premotor area, right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex, and bilateral temporal and occipital regions. The OCD patients also showed a significant WM volume increase in the right anterior limb of the internal capsule, right orbitofrontal region, and a significant WM volume reduction in the left anterior cingulate gyrus. Our findings are consistent with previous studies implicating dysfunction of the frontal cortex including the OFC. The results suggested that WM volume abnormalities in the orbitofrontal region, anterior limb of the internal capsule, and anterior cingulate gyrus would imply abnormalities in the pathways of frontal-striatal circuits.

[Optimal volume of medicinal solution in the portable disposable infusion pump (SUREFUSER A) for FOLFOX6, FOLFIRI therapy of colorectal cancer patients (2nd report)-influence of temperature on outflow speed of the medicinal solution].

We formerly reported the most suitable volumes of medicinal solution for continuous 5FU infusion over 46 hours in the FOLFOX6 and FOLFIRI regimens, respectively, by analyzing the relation of the total volume of the medicinal solution in a portable disposable infusion pump (SUREFUSER A) and the duration of infusion using a regression analysis. A total infusion time of about 48 hours was obtained. As the ambient temperature increased, however, we noticed that the continuous 5FU infusion finished earlier than anticipated. Using an additional analysis, we found that not only the medicinal solution's original coefficient of viscosity, but also the ambient temperature influenced the duration of infusion. Here, we report that the speed of continuous 5FU infusion increases as the coefficient of viscosity decreases in response to increases in ambient temperature. Thus, the composition of medicinal solutions and the ambient temperature must be considered to ensure a correct duration of continuous infusion.

The effect of facial hair whorl position and raising environment on the temperament of the Chinese Yellow cattle in Shinjang Uyghur Aptonom Rayoni, China.

OBJECTIVE: The objective of this study is to determine whether there is a relationship between hair whorl position and temperament in Chinese Yellow cattle using a questionnaire. Also, the effect of the raising environment is investigated. MATERIALS AND METHODS: A total of 122 Chinese Yellow cattle were surveyed in 3 village areas and four grassland areas in the northern area of China. For each cattle, an investigator asked the care-person about each item of a temperament questionnaire and determined the facial hair whorl position of each cattle. The location of hair whorl was categorized as low, middle, or high in relation to the eyes. RESULTS: The overall distribution was 20.5% high, 58.2% middle, 13.1% low, 6.6% double, and 1.6% no hair whorl. There was no significant difference between the grassland and village area cattle in the distribution of whorl position. The scores of grassland areas were significantly higher than those of village areas in terms of "Retentive memory", "Sensitivity," and "Timidity" and lower in "Docility" and "Fortitude." The scores for the high position tended to be higher than those for the middle plus low positions in terms of "Adaptability" and "Obedience." On the other hand, there was a tendency for a score for the high position to be lower than the other positions in "Excitability." A significant interaction between area and whorl position was observed in "Friendliness to cattle." CONCLUSION: These findings suggest that hair whorl location may be useful in predicting the temperament in cattle, but temperament can be influenced by environment and/or handlings.

Association between temperament and polymorphisms of CRH and leptin in Japanese Black Cattle.

OBJECTIVE: The behavioral trait is one of the important concerns when handling livestock. The objectives of the present study were investigated the possible role of these genes on behavioral traits in Japanese Black cattle (Bos taurus). MATERIALS AND METHODS: Blood samples were collected for DNA extraction and genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism method. Two energy metabolism related genes, namely, corticotropin-releasing hormone (CRH) and leptin (LEP) were subjected in this work. Temperaments were evaluated by scores of four behavioral tests. RESULTS: Allele frequencies for the C and G alleles at CRH were 0.25 and 0.75, respectively. For the LEP SNP, the C and T alleles were 0.71 and 0.29, respectively. By analyzing the association between the polymorphisms and temperament scores of behavioral tests, significant effects of CRH polymorphism and interaction were not detected but cattle with wild homo-type of LEP tended to permit the contact of stranger when feeding (p < 0.1). CONCLUSION: These findings suggest that the LEP polymorphism is involved in behavioral traits in Japanese Black cattle. The LEP polymorphism may be useful in selecting Japanese Black cattle with the trait of being docility.

Long-Term Effectiveness and Cost-Effectiveness of Videoconference-Delivered Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder in Japan: One-Year Follow-Up of a Single-Arm Trial.

BACKGROUND: Face-to-face individual cognitive behavioral therapy (CBT) and internet-based CBT (ICBT) without videoconferencing are known to have long-term effectiveness for obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). However, videoconference-delivered CBT (VCBT) has not been investigated regarding its long-term effectiveness and cost-effectiveness. OBJECTIVE: The purpose of this study was to investigate the long-term effectiveness and cost-effectiveness of VCBT for patients with OCD, PD, or SAD in Japan via a 1-year follow-up to our previous 16-week single-arm study. METHODS: Written informed consent was obtained from 25 of 29 eligible patients with OCD, PD, and SAD who had completed VCBT in our clinical trial. Participants were assessed at baseline, end of treatment, and at the follow-up end points of 3, 6, and 12 months. Outcomes were the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Panic Disorder Severity Scale (PDSS), Liebowitz Social Anxiety Scale (LSAS), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), and EuroQol-5D-5L (EQ-5D-5L). To analyze long-term effectiveness, we used mixed-model analysis of variance. To analyze cost-effectiveness, we employed relevant public data and derived data on VCBT implementation costs from Japanese national health insurance data. RESULTS: Four males and 21 females with an average age of 35.1 (SD 8.6) years participated in the 1-year follow-up study. Principal diagnoses were OCD (n=10), PD (n=7), and SAD (n=8). The change at 12 months on the Y-BOCS was -4.1 (F1=4.45, P=.04), the change in PDSS was -4.4 (F1=6.83, P=.001), and the change in LSAS was -30.9 (F1=6.73, P=.01). The change in the PHQ-9 at 12 months was -2.7 (F1=7.72, P=.007), and the change in the GAD-7 was -3.0 (F1=7.09, P=.009). QALY at 12 months was 0.7469 (SE 0.0353, 95% Cl 0.6728-0.821), and the change was a significant increase of 0.0379 (P=.01). Total costs to provide the VCBT were ¥60,800 to ¥81,960 per patient. The set threshold was ¥189,500 ($1723, €1579, and £1354) calculated based on willingness to pay in Japan. CONCLUSIONS: VCBT was a cost-effective way to effectively treat Japanese patients with OCD, PD, or SAD. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000026609; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030495.