Development and validation of the Japanese version of the Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale.

INTRODUCTION: The Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale (LGBT-DOCSS) is a validated self-assessment tool for health and mental health professionals who provide healthcare for sexual and gender minority patients. This study aimed to develop and validate a Japanese version of LGBT-DOCSS (LGBT-DOCSS-JP) and examine its psychometric properties. METHODS: LGBT-DOCSS was translated into Japanese and cross-culturally validated using cognitive debriefing. We then evaluated the structural validity, convergent and discriminant validity, internal consistency, and test-retest reliability of LGBT-DOCSS-JP using an online survey. RESULTS: Data were analyzed for 381 health and mental health professionals aged 20 years or older from three suburban medical institutions. The confirmatory factor analysis indicated that the original three-factor model did not fit well with LGBT-DOCSS-JP. Exploratory factor analysis revealed four new factors: Attitudinal Awareness, Basic Knowledge, Clinical Preparedness, and Clinical Training. Convergent and discriminant validity were supported using four established scales that measured attitudes toward lesbians and gay men, genderism and transphobia, authoritarianism and conventionalism, and social desirability. The internal consistency of LGBT-DOCSS-JP was supported by the Cronbach's alpha values for the overall scale (0.84), and for each of its subscales (Attitudinal Awareness and Basic Knowledge both 0.87, Clinical Preparedness 0.78, and Clinical Training 0.97). The test-retest reliability for the overall LGBT-DOCSS-JP was supported by an intraclass correlation coefficient score of 0.86. CONCLUSIONS: LGBT-DOCSS-JP has the potential to serve as a valuable tool in the development and assessment of effective curricula for LGBT healthcare education, as well as a means to promote self-reflection among trainees and professionals.

Social anxiety disorder in adolescents who stutter: A risk for school refusal.

BACKGROUND: Stuttering is a childhood-onset fluency disorder. Part of the counseling for middle and high school students with persistent stuttering is related to school refusal. Anxiety disorders are known to contribute to school refusal. However, it is not known whether social anxiety disorder (SAD) is a factor in school refusal among adolescents who stutter. METHODS: In our first study, we examined the relationship between school refusal and SAD in 84 middle and high school students who stutter; 26% of the 84 students were in the school refusal group and the remaining 74% were in the school attendance group. The second study examined whether SAD was associated with 10 factors related to speech and stuttering frequency using the Japanese version of the Liebowitz Social Anxiety Scale for Children and Adolescents to determine the presence of SAD. Of the 84 students in the first study, 40 participated in the second study. RESULTS: The school refusal group of adolescents who stutter had significantly higher rates of SAD than the school attendance group. Fifty percent of adolescents who stutter met the criteria for SAD. Moreover, adolescents who stutter with SAD had significantly higher scores on the items "When speaking in public, do you experience tremors in your limbs?" and "After you stutter, do you have negative thoughts about yourself?" than the adolescents who stutter without SAD. CONCLUSIONS: When examining adolescents who stutter, checking for comorbid SAD may lead to better support. Moreover, noticing their repetitive negative thinking, nervousness, and trembling during speech may help to resolve SAD.

Management of unspecified anxiety disorder: Expert consensus.

AIMS: Treatment guidelines with respect to unspecified anxiety disorder have not been published. The aim of this study was to develop a consensus among field experts on the management of unspecified anxiety disorder. METHODS: Experts were asked to evaluate treatment choices based on eight clinical questions concerning unspecified anxiety disorder using a nine-point Likert scale (1 = "disagree" to 9 = "agree"). According to the responses from 119 experts, the choices were categorized into first-, second-, and third-line recommendations. RESULTS: Benzodiazepine anxiolytic use was not categorized as a first-line recommendation for the primary treatment of unspecified anxiety disorder, whereas multiple nonpharmacological treatment strategies, including coping strategies (7.9 ± 1.4), psychoeducation for anxiety (7.9 ± 1.4), lifestyle changes (7.8 ± 1.5), and relaxation techniques (7.4 ± 1.8), were categorized as first-line recommendations. Various treatment strategies were categorized as first-line recommendations when a benzodiazepine anxiolytic drug did not improve anxiety symptoms, that is, differential diagnosis (8.2 ± 1.4), psychoeducation for anxiety (8.0 ± 1.5), coping strategies (7.8 ± 1.5), lifestyle changes (7.8 ± 1.5), relaxation techniques (7.2 ± 1.9), and switching to selective serotonin reuptake inhibitors (SSRIs) (7.0 ± 1.8). These strategies were also highly endorsed when tapering the dosage of or discontinuing benzodiazepine anxiolytic drugs. There was no first-line recommendation regarding excusable reasons for continuing benzodiazepine anxiolytics. CONCLUSIONS: The field experts recommend that benzodiazepine anxiolytics should not be used as a first-line option for patients with unspecified anxiety disorder. Instead, several nonpharmacological interventions and switching to SSRIs were endorsed for the primary treatment of unspecified anxiety disorder and as alternatives to benzodiazepine anxiolytics.

Glove-shaped Foam with Negative Pressure Wound Therapy for Skin Graft Fixation on the Hand.

Tie-over bolster dressing has been the gold standard for skin graft immobilization. However, skin grafting onto the hand remains challenging. To prevent shearing of the skin, joint fixation with Kirschner wire and casting is often required. However, wire fixation through the joint can disrupt finger growth and cause joint contracture, especially in pediatric patients. So, we performed graft fixation with negative pressure wound therapy (NPWT). The use of NPWT with skin grafting has recently been reported. Previous studies have reported that NPWT can provide even pressure on irregular wounds and in highly mobile areas. However, application of NPWT in the digital region often results in air leaks. This report includes four patients who required skin grafting on the hand. All patients received skin grafts in the affected area. Graft fixation was performed with NPWT. A glove-shaped form was designed. The hand was encased on the ventral and dorsal sides and small pieces of foam were placed between the fingers. The fixation was maintained for 7 days at a pressure of -50 to -80 mmHg. None of the cases had air leak requiring reattachment of the system and graft take was successful in all cases without any complications. The NPWT "glove-shape" technique enabled maintenance of average negative pressure for all skin grafts on the hand. This technique does not require joint fixation and may help to prevent growth disturbance and joint contracture.

Chronic Intake of a Meal Including Alaska Pollack Protein Increases Skeletal Muscle Mass and Strength in Healthy Older Women: A Double-Blind Randomized Controlled Trial.

BACKGROUND: In animal studies, a meal containing Alaska pollack protein (APP) induces fast-twitch muscle hypertrophy. To our knowledge, no interventional studies have examined the benefits of APP intake on muscle mass and muscle weakness and the prevention of sarcopenia in older individuals. OBJECTIVES: We evaluated the effects of APP intake on skeletal muscle mass, muscle strength, and physical performance among healthy community-dwelling older Japanese women. METHODS: In this double-blind randomized controlled trial, healthy women ≥ 65 y old were allocated to an APP or whey protein control (CON) group. Participants ingested test protein meals (5.0-5.1 g protein/serving) daily for 24 wk. Between-group differences in the change of skeletal muscle mass index (SMI) as the primary outcome and muscle strength as a secondary outcome were tested using multifrequency BIA and a handheld dynamometer, respectively, at baseline, and 4, 12, and 24 wk. The mean changes in the measured primary and secondary outcome variables from baseline to 4, 12, and 24 wk were compared using unpaired t tests. RESULTS: There were no between-group differences in nutritional status, food intake, or total energy and protein intakes at baseline, 12 wk, or 24 wk. The change in SMI was 0.12 kg/m2 (95% CI: 0.01, 0.23 kg/m2) and 0.11 kg/m2 (95% CI: 0.03, 0.19 kg/m2) greater in the APP group than in the CON group at 12 wk and 24 wk (P ≤ 0.03) and knee extension strength was 0.07 Nm/kg BW (95% CI: 0.02, 0.12 Nm/kg BW) and 0.05 Nm/kg BW (95% CI: 0.00, 0.09 Nm/kg BW) higher in the APP group than in the CON group at these times (P ≤ 0.015), respectively. The groups did not differ at 4 wk. CONCLUSIONS: Daily intake of a meal containing APP compared with whey protein increases skeletal muscle mass and lower-extremity muscle strength in healthy older women, suggesting that an APP-containing meal may be useful in the prevention of sarcopenia in this group.This trial was registered at as UMIN000035718.

New Notations for Better Morphological Distinction of Postaxial Polydactyly of the Foot.

There have been many reports on the classification and treatment of postaxial polydactyly of the foot. However, despite its being a common congenital anomaly, there is no universal notation about its morphology. Methods: We performed an analysis of 65 postaxial polydactyly cases from 2004 to 2021. Judgment criteria for deciding the surgical procedure were selected, and the points required for notation were decided. Based on them, we devised a new notation. Results: The necessary points required for notation were decided based on the following criteria: (1) the presence and level of syndactyly, (2) bifurcation level of the phalanges, (3) the presence of other deformities, and (4) predominant toes. We came up with a new notation and description method. Different types of syndactyly were represented using a horizontal bar, and predominant toes were represented using equality or inequality symbols. The bifurcation level of the phalanges and accessory deformities were additionally recorded (eg, 4-5>-6, Middle, 5,6: External rotation). From this notation, it is obvious which toe should be resected. Furthermore, syndactyly, accessory deformities, and the condition of the phalanges are also easily understood. Conclusions: Our new notation for postaxial polydactyly consists of some related symbols that are each provided a meaning. This system is simple, especially for easily understanding the morphology, and ideal for daily medical use. We conclude that it could become a universal notation method for cases of postaxial polydactyly of the foot.

Cross-sectional survey of education on LGBT content in medical schools in Japan.

OBJECTIVES: We aimed to clarify current teaching on lesbian, gay, bisexual, transgender (LGBT) content in Japanese medical schools and compare it with data from the USA and Canada reported in 2011 and Australia and New Zealand reported in 2017. DESIGN: Cross-sectional study. SETTING: Eighty-two medical schools in Japan. PARTICIPANTS: The deans and/or relevant faculty members of the medical schools in Japan. PRIMARY OUTCOME MEASURE: Hours dedicated to teaching LGBT content in each medical school. RESULTS: In total, 60 schools (73.2%) returned a questionnaire. One was excluded because of missing values, leaving 59 responses (72.0%) for analysis. In total, LGBT content was included in preclinical training in 31 of 59 schools and in clinical training in 8 of 53 schools. The proportion of schools that taught no LGBT content in Japan was significantly higher than that in the USA and Canada, both in preclinical and clinical training (p<0.01). The median time dedicated to LGBT content was 1 hour (25th-75th percentile 0-2 hours) during preclinical training and 0 hour during clinical training (25th-75th percentile 0-0 hour). Only 13 schools (22%) taught students to ask about same-sex relations when obtaining a sexual history. Biomedical topics were more likely to be taught than social topics. In total, 45 of 57 schools (79%) evaluated their coverage of LGBT content as poor or very poor, and 23 schools (39%) had some students who had come out as LGBT. Schools with faculty members interested in education on LGBT content were more likely to cover it. CONCLUSION: Education on LGBT content in Japanese medical schools is less established than in the USA and Canada.

Development of Alveolar Hemorrhage After Pfizer-BioNTech COVID-19 mRNA Vaccination in a Patient With Renal-Limited Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Case Report.

Since the coronavirus disease 2019 (COVID-19) pandemic continues and a new variant of the virus has emerged, the COVID-19 vaccination campaign has progressed. Rare but severe adverse outcomes of COVID-19 vaccination such as anaphylaxis and myocarditis have begun to be noticed. Of note, several cases of new-onset antineutrophil cytoplasmic antibody-associated vasculitis (AAV) after COVID-19 mRNA vaccination have been reported. However, relapse of AAV in remission has not been recognized enough as an adverse outcome of COVID-19 vaccination. We report, to our knowledge, a first case of renal-limited AAV in remission using every 6-month rituximab administration that relapsed with pulmonary hemorrhage, but not glomerulonephritis, following the first dose of the Pfizer-BioNTech COVID-19 vaccine. The patient received the COVID-19 vaccine more than 6 months after the last dose of rituximab according to the recommendations. However, his CD19+ B cell counts were found to be increased after admission, indicating that our case might have been prone to relapse after COVID-19 vaccination. Although our case cannot establish causality between AAV relapse and COVID-19 mRNA vaccination, a high level of clinical vigilance for relapse of AAV especially in patients undergoing rituximab maintenance therapy following COVID-19 vaccination should be maintained. Furthermore, elapsed time between rituximab administration and COVID-19 mRNA vaccination should be carefully adjusted based on AAV disease-activity.

Fish Protein Promotes Skeletal Muscle Hypertrophy via the Akt/mTOR Signaling Pathways.

Skeletal muscle is the largest organ in the body and has a broad range of plasticity, undergoing atrophy in response to aging or disease and hypertrophy in response to nutritional supplements or exercise. Loss of skeletal muscle mass and force increases the risk of falls, impairs mobility, and leads to reduced quality of life. In a previous study, we demonstrated that taking in Alaska pollock protein (APP) for only 7 d increased the gastrocnemius muscle mass in rats. This study was conducted to identify hypertrophic myofibers and analyze how hypertrophy occurs within them. Twenty male rats were randomly divided into two groups and administered a diet of casein or APP for 7 d. The expression of each myosin heavy chain (MyHC) isoform in a cross-sectional area was then measured. MyHC IIb and IIx isoforms exhibited hypertrophic features in the gastrocnemius muscles of the APP-fed rats. Furthermore, comprehensive proteomic analyses were conducted to identify changes in protein expression due to muscle hypertrophy. Our results, evaluated by pathway analyses, indicated that the activity of the growth factor signaling pathway was significantly impacted by APP consumption. Moreover, APP could promote protein synthesis by activating the protein kinase B/mechanistic target of the rapamycin signaling pathway, which is also promoted by exercise.

Non-action Learning: Saving Action-Associated Cost Serves as a Covert Reward.

"To do or not to do" is a fundamental decision that has to be made in daily life. Behaviors related to multiple "to do" choice tasks have long been explained by reinforcement learning, and "to do or not to do" tasks such as the go/no-go task have also been recently discussed within the framework of reinforcement learning. In this learning framework, alternative actions and/or the non-action to take are determined by evaluating explicitly given (overt) reward and punishment. However, we assume that there are real life cases in which an action/non-action is repeated, even though there is no obvious reward or punishment, because implicitly given outcomes such as saving physical energy and regret (we refer to this as "covert reward") can affect the decision-making. In the current task, mice chose to pull a lever or not according to two tone cues assigned with different water reward probabilities (70% and 30% in condition 1, and 30% and 10% in condition 2). As the mice learned, the probability that they would choose to pull the lever decreased (<0.25) in trials with a 30% reward probability cue (30% cue) in condition 1, and in trials with a 10% cue in condition 2, but increased (>0.8) in trials with a 70% cue in condition 1 and a 30% cue in condition 2, even though a non-pull was followed by neither an overt reward nor avoidance of overt punishment in any trial. This behavioral tendency was not well explained by a combination of commonly used Q-learning models, which take only the action choice with an overt reward outcome into account. Instead, we found that the non-action preference of the mice was best explained by Q-learning models, which regarded the non-action as the other choice, and updated non-action values with a covert reward. We propose that "doing nothing" can be actively chosen as an alternative to "doing something," and that a covert reward could serve as a reinforcer of "doing nothing."

The need for home care physicians in Japan - 2020 to 2060.

BACKGROUND: Japan faces the most elderly society in the world, and the Japanese government has launched an unprecedented health plan to reinforce home care medicine and increase the number of home care physicians, which means that an understanding of future needs for geriatric home care is vital. However, little is known about the future need for home care physicians. We attempted to estimate the basic need for home care physicians from 2020 to 2060. METHODS: Our estimation is based on modification of major health work force analysis methods using previously reported official data. Two models were developed to estimate the necessary number of full-time equivalent (FTE) home care physicians: one based on home care patient mortality, the other using physician-to-patient ratio, working with estimated numbers of home and nursing home deaths from 2020 to 2060. Moreover, the final process considered and adjusted for future changes in the proportion of patients dying at home. Lastly, we converted estimated FTE physicians to an estimated head count. RESULTS: Results were concordant between our two models. In every instance, there was overlap of high- and low-estimations between the mortality method and the physician-to-patient method, and the estimates show highly similar patterns. Furthermore, our estimation is supported by the current number of physicians, which was calculated using a different method. Approximately 1.7 times (1.6 by head count) the current number of FTE home care physicians will be needed in Japan in the late 2030's, peaking at 33,500 FTE (71,500 head count). However, the need for home care physicians is anticipated to begin decreasing by 2040. CONCLUSION: The results indicate that the importance of home care physicians will rise with the growing elderly population, and that improvements in home care could partially suppress future need for physicians. After the late 2030's, the supply can be reduced gradually, accounting for the decreasing total number of deaths after 2040. In order to provide sufficient home care and terminal care at home, increasing the number of home care physicians is indispensable. However, the unregulated supply of home care physicians will require careful attention in the future.

Depression and anxiety in pet owners after a diagnosis of cancer in their pets: a cross-sectional study in Japan.

OBJECTIVE: To determine the presence and predictors of depression and anxiety in pet owners after a diagnosis of cancer in their pets. DESIGN: Cross-sectional study. SETTING: A veterinary medical centre specialised in oncology for dogs and cats and two primary veterinary clinics in Japan. PARTICIPANTS: The participants for analysis were 99 owners of a pet with cancer diagnosis received in the past 1-3 weeks and 94 owners of a healthy pet. MAIN OUTCOME MEASURES: Self-reported questionnaires were used to assess depression and anxiety. Depression was assessed using the Center of Epidemiologic Studies Depression Scale, and anxiety was measured by using the State-Trait Anxiety Inventory-Form JYZ. RESULTS: Depression scores were significantly higher in owners of a pet with cancer than owners of a healthy pet, even after adjustment for potential confounders (p<0.001). Within the owners of a pet with cancer, depression was significantly more common in those who were employed than those who were unemployed (p=0.048). State anxiety scores were significantly higher in owners of a pet with cancer than owners of a healthy pet, even after adjustment for potential confounders, including trait-anxiety scores (p<0.001). Furthermore, in owners of a pet with cancer, state anxiety was higher in owners with high trait anxiety (p<0.001) and in owners whose pets had a poor prognosis (p=0.027). CONCLUSION: The results indicate that some owners tended to become depressed and anxious after their pets had received a diagnosis of cancer. Employment may be a predictor of depression. High trait anxiety and a pet with a poor prognosis may increase owners' state anxiety. Including the pet in a family genogram and attention to the pet's health condition may be important considerations for family practice.

In vivo wide-field calcium imaging of mouse thalamocortical synapses with an 8 K ultra-high-definition camera.

In vivo wide-field imaging of neural activity with a high spatio-temporal resolution is a challenge in modern neuroscience. Although two-photon imaging is very powerful, high-speed imaging of the activity of individual synapses is mostly limited to a field of approximately 200 µm on a side. Wide-field one-photon epifluorescence imaging can reveal neuronal activity over a field of ≥1 mm2 at a high speed, but is not able to resolve a single synapse. Here, to achieve a high spatio-temporal resolution, we combine an 8 K ultra-high-definition camera with spinning-disk one-photon confocal microscopy. This combination allowed us to image a 1 mm2 field with a pixel resolution of 0.21 µm at 60 fps. When we imaged motor cortical layer 1 in a behaving head-restrained mouse, calcium transients were detected in presynaptic boutons of thalamocortical axons sparsely labeled with GCaMP6s, although their density was lower than when two-photon imaging was used. The effects of out-of-focus fluorescence changes on calcium transients in individual boutons appeared minimal. Axonal boutons with highly correlated activity were detected over the 1 mm2 field, and were probably distributed on multiple axonal arbors originating from the same thalamic neuron. This new microscopy with an 8 K ultra-high-definition camera should serve to clarify the activity and plasticity of widely distributed cortical synapses.

Identification and enzymatic characterization of an endo-1,3-ß-glucanase from Euglena gracilis.

Euglena produces paramylon as a storage polysaccharide, and is thought to require ß-1,3-glucan degrading enzymes to release and utilize the accumulated carbohydrate. To investigate ß-1,3-glucan degradation in Euglena, endo-1,3-ß-glucanases were partially purified from Euglena gracilis by hydrophobic, gel filtration and anion-exchange chromatography. Tryptic digests and mass-spectrometric analysis identified three proteins in the purified fraction as a member of glycoside hydrolase family (GH) 17 and two members of GH81. These genes were cloned from an Euglena cDNA pool by PCR. EgCel17A fused with a histidine-tag at the carboxy terminus was heterologously produced by Aspergillus oryzae and purified by immobilized metal affinity chromatography. Purified EgCel17A had a molecular weight of about 40kDa by SDS-PAGE, which was identical to that deduced from its amino acid sequence. The enzyme showed hydrolytic activity towards ß-1,3-glucans such as laminarin and paramylon. Maximum activity of laminarin degradation by EgCel17A was attained at pH 4.0-5.5 and 60°C after 1h incubation or 50°C after 20h incubation. The enzyme had a Km of 0.21mg/ml and a Vmax of 40.5units/mg protein for laminarin degradation at pH 5.0 and 50°C. Furthermore, EgCel17A catalyzed a transglycosylation reaction by which reaction products with a higher molecular weight than the supplied substrates were initially generated; however, ultimately the substrates were degraded into glucose, laminaribiose and laminaritriose. EgCel17A effectively produced soluble ß-1,3-glucans from alkaline-treated Euglena freeze-dried powder containing paramylon. Thus, EgCel17 is the first functional endo-1,3-ß-glucanase to be identified from E. gracilis.

Enhancement of photosynthetic capacity in Euglena gracilis by expression of cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase leads to increases in biomass and wax ester production.

BACKGROUND: Microalgae have recently been attracting attention as a potential platform for the production of biofuels. Euglena gracilis, a unicellular phytoflagellate, has been proposed as an attractive feedstock to produce biodiesel because it can produce large amounts of wax esters, consisting of medium-chain fatty acids and alcohols with 14:0 carbon chains. E. gracilis cells highly accumulate a storage polysaccharide, a ß-1,3-glucan known as paramylon, under aerobic conditions. When grown aerobically and then transferred into anaerobic conditions, E. gracilis cells degrade paramylon to actively synthesize and accumulate wax esters. Thus, the enhanced accumulation of paramylon through the genetic engineering of photosynthesis should increase the capacity for wax ester production. RESULTS: We herein generated transgenic Euglena (EpFS) cells expressing the cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase (FBP/SBPase), which is involved in the Calvin cycle, to enhance its photosynthetic activity. FBP/SBPase was successfully expressed within Euglena chloroplasts. The cell volume of the EpFS4 cell line was significantly larger than that of wild-type cells under normal growth conditions. The photosynthetic activity of EpFS4 cells was significantly higher than that of wild type under high light and high CO2, resulting in enhanced biomass production, and the accumulation of paramylon was increased in transgenic cell lines than in wild-type cells. Furthermore, when EpFS cell lines grown under high light and high CO2 were placed on anaerobiosis, the productivity of wax esters was approximately 13- to 100-fold higher in EpFS cell lines than in wild-type cells. CONCLUSION: Our results obtained here indicate that the efficiency of biomass production in E. gracilis can be improved by genetically modulating photosynthetic capacity, resulting in the enhanced production of wax esters. This is the first step toward the utilization of E. gracilis as a sustainable source for biofuel production under photoautotrophic cultivation.

Congenital multiple intrahepatic portosystemic shunt: an autopsy case.

Multiple intrahepatic portosystemic shunt (IPSS) without portal hypertension, now thought to be congenital in origin, is very rare. The presence of IPSS, unlike other congenital diseases, may not be recognized for several decades due to the time it takes to develop hepatic encephalopathy. In this article, we report an autopsy case of an 80-year-old Japanese woman with a one-month history of hyperammonemic encephalopathy. Radiological examination of the liver revealed some abnormal connections between the branches of the portal veins and the hepatic veins, but the cause of the aberrant blood flow was not found. The cause of death was extensive cerebral infarction due to thromboembolism. At postmortem examination, multiple anomalous blood vessels were identified histologically in both lobes of the non-cirrhotic liver. In comparison with the few similar cases existing in the literature, this case should be diagnosed as congenital IPSS. To our knowledge, this is the first detailed histological study of IPSS, as several autopsy case reports exist but their histological descriptions are poor. Unlike past reports, the shunt vessels were accompanied by clear elastic lamellae that were microscopically observed. In addition to shunt vessels, septal fibrosis, disorder of hepatic acinar structure, and sinusoidal dilatation and capillarization were observed in the liver. We suggest that these histological modifications observed in the circumference of the shunt vessels acted as secondary regenerative/hyperplastic changes based on blood-flow imbalance caused by the IPSS.

Antitumor activity of the ß-glucan paramylon from Euglena against preneoplastic colonic aberrant crypt foci in mice.

In the present study, the effects of ß-glucans isolated from Euglena on the formation of preneoplastic aberrant crypt foci (ACF) in the colon were examined in mice. Mice were fed a semi-purified AIN-93M diet containing cellulose or the same diet but with the cellulose replaced with ß-glucans in the form of Euglena, paramylon, or amorphous paramylon, for 11 weeks. After consuming these dietary supplements for 8 days, half of the mice were intraperitoneally administered 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) body weight every week for 6 weeks. Among the DMH-treated groups, the paramylon- and amorphous paramylon-fed mice displayed a significantly lower number of ACF than the control group. Also, the liver weight of the paramylon group was markedly decreased compared with those of the control and Euglena groups, whereas the cecal content weight and fecal volume of the paramylon group were significantly increased. As for the levels of organic acids in the cecal contents, the paramylon group displayed significantly increased lactic acid levels compared with the control and Euglena groups. From these findings, although the mechanism of the ACF-inhibiting effects of paramylon remains unclear, it is considered that ß-glucans, such as paramylon and its isomer amorphous paramylon, have preventive effects against colon cancer and are more effective against the condition than Euglena.

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative.

The cis- and trans-stereoselective radical additions to α-methylene-γ-alkyl- γ-lactams were investigated and the scope and limitation of the reaction were also revealed. This stereoselective radical reaction was used for synthesis of chiral pyroglutamic acid derivatives starting from a commercially available chiral amino acid.

The 26S proteasome function and Hsp90 activity involved in the regulation of HsfA2 expression in response to oxidative stress.

Heat shock transcription factor A2 (HsfA2) is induced under environmental stress and regulates transcription of various defense-related genes. Thus HsfA2 plays an important role in induction of defenses against different types of environmental stress, but its mode of regulation remains unknown. To clarify the signal transduction pathway involved in the regulation of HsfA2 expression, we investigated the effect of MG132, a 26S proteasome inhibitor, or geldanamycin (GDA), a heat shock protein 90 (Hsp90) inhibitor, on the transcription of HsfA2 and its targets, Hsp18.1-CI and ascorbate peroxidase 2 (Apx2), in Arabidopsis T87 cells. The levels of transcripts were significantly increased by treatment with MG132 or GDA. Overexpression of a dexamethazone-inducible dominant-negative form of Hsp90.2 in Arabidopsis plants caused significant expression of HsfA2 and its target gene on treatment with the compound. Treatment with MG132 or GDA had no effect on intracellular levels of reactive oxygen species (ROS). Interestingly, the levels of polyubiquitinated proteins as well as the levels of HsfA2 transcript were rapidly increased under oxidative stress derived from treatment with H2O2 or methylviologen, while they were completely suppressed by pre-treatment with ascorbate, a scavenger of ROS, under oxidative stress. The present findings suggest that the inhibition of 26S proteasome function and/or Hsp90 activity is involved in the induction of HsfA2 expression in response to oxidative stress.