Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study.

The psychopathology of patients with anorexia nervosa has been hypothesized to involve inappropriate self-referential processing, disturbed interoceptive awareness, and excessive cognitive control, including distorted self-concern, disregard of their own starvation state, and extreme weight-control behavior. We hypothesized that the resting-state brain networks, including the default mode, salience and frontal-parietal networks, might be altered in such patients, and that treatment might normalize neural functional connectivity, with improvement of inappropriate self-cognition. We measured resting-state functional magnetic resonance images from 18 patients with anorexia nervosa and 18 healthy subjects before and after integrated hospital treatment (nourishment and psychological therapy). The default mode, salience, and frontal-parietal networks were examined using independent component analysis. Body mass index and psychometric measurements significantly improved after treatment. Before treatment, default mode network functional connectivity in the retrosplenial cortex and salience network functional connectivity in the ventral anterior insula and rostral anterior cingulate cortex were decreased in anorexia nervosa patients compared with those in controls. Interpersonal distrust was negatively correlated with salience network functional connectivity in the rostral anterior cingulate cortex. Default mode network functional connectivity in the posterior insula and frontal-parietal network functional connectivity in the angular gyrus were increased in anorexia nervosa patients compared with those in controls. Comparison between pre- and post-treatment images from patients with anorexia nervosa exhibited significant increases in default mode network functional connectivity in the hippocampus and retrosplenial cortex, and salience network functional connectivity in the dorsal anterior insula following treatment. Frontal-parietal network functional connectivity in the angular cortex showed no significant changes. The findings revealed that treatment altered the functional connectivity in several parts of default mode and salience networks in patients with anorexia nervosa. These alterations of neural function might be associated with improvement of self-referential processing and coping with sensations of discomfort following treatment for anorexia nervosa.

Investigation of radical scavenging effects of acetaminophen, p-aminophenol and their O-sulfated conjugates.

Acetaminophen (APAP) and p-aminophenol (p-AP) are the analogous simple phenolic compounds that undergo sulfate conjugation (sulfation) by cytosolic sulfotransferases. Sulfation is generally thought to lead to the inactivation and disposal of endogenous as well as xenobiotic compounds. This study aimed to investigate the antioxidative effects of O-sulfated form of APAP and p-AP, i.e., APAPS and p-APS, in comparison with their unsulfated counterparts. Using a 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay, the antioxidant capacity of APAPS was shown to be approximately 126-times lower than that of APAP. In contrast, p-APS displayed comparable activity as unsulfated p-AP. Similar trends concerning the suppressive effects of these chemicals on cellular O2- radical generation were found using an activated granulocytic neutrophil cell model. Collectively, these results indicated that, depending on the presence of an additional "active site", sulfation may not always decrease the antioxidant activities of phenolic compounds.

Metabolomics profile of Japanese female patients with restricting-type anorexia nervosa.

In this study, the serum metabolic profiles of 10 female patients with restricting type anorexia nervosa (ANR) were compared to those of 10 age-matched healthy female controls. While the levels of amino acids were lower among the patients than among the controls, the levels of uremic toxins, including p-cresyl sulfate (PCS), indole-3-acetic acid, and phenyl sulfate, were higher in ANR patients. The serum PCS levels correlated positively with the abundance of the Clostridium coccoides group or the C. leptum subgroup in the feces of patients, but not in those of controls. Collectively, these results indicate that the serum metabolic profiles of patients with ANR differ from those of healthy women in terms of both decreased amino acid levels and increased uremic toxins. Gut microbes including C. coccoides or C. leptum may be involved in such an increase in uremic toxins.

Prenylated Acetophloroglucinol Dimers from Acronychia trifoliolata: Structure Elucidation and Total Synthesis.

The isolation of 12 secondary metabolites, including seven new acetophenone monomers, from the 50% CH3OH/CH2Cl2 extract (N089419-L/6) of Acronychia trifoliolata was reported previously. In the present work, three new prenylated acetophenone dimers (1-3) and five known dimers (4-8) were isolated, and their structures were elucidated by using various NMR spectroscopic techniques and HRMS. Among the new dimers, an unprecedented 4-isobutyl-3-isopropyltetrahydro-2H-pyran ring was observed in the structure of 1. This study is the first to report the formation of a 2H-pyran ring between two prenylated acetophloroglucinols. Only four related dimers have been reported before, and they were formylated phloroglucinol dimers from the family Eucalypteae. Compounds 2 and 3 are acrovestone-like dimers, and the structure of 3 was confirmed by total synthesis. The evaluation of the antiproliferative activity of isolated and synthesized acrovestone-like dimers indicated that a double bond in the prenyl-like moiety as found in the more active compounds might be important for mediating activity, while the pendant isobutyl group seems to be less important.

Acrolein-detoxifying isozymes of glutathione transferase in plants.

MAIN CONCLUSION: Acrolein is a lipid-derived highly reactive aldehyde, mediating oxidative signal and damage in plants. We found acrolein-scavenging glutathione transferase activity in plants and purified a low K M isozyme from spinach. Various environmental stressors on plants cause the generation of acrolein, a highly toxic aldehyde produced from lipid peroxides, via the promotion of the formation of reactive oxygen species, which oxidize membrane lipids. In mammals, acrolein is scavenged by glutathione transferase (GST; EC 2.5.1.18) isozymes of Alpha, Pi, and Mu classes, but plants lack these GST classes. We detected the acrolein-scavenging GST activity in four species of plants, and purified an isozyme showing this activity from spinach (Spinacia oleracea L.) leaves. The isozyme (GST-Acr), obtained after an affinity chromatography and two ion exchange chromatography steps, showed the K M value for acrolein 93 µM, the smallest value known for acrolein-detoxifying enzymes in plants. Peptide sequence homology search revealed that GST-Acr belongs to the GST Tau, a plant-specific class. The Arabidopsis thaliana GST Tau19, which has the closest sequence similar to spinach GST-Acr, also showed a high catalytic efficiency for acrolein. These results suggest that GST plays as a scavenger for acrolein in plants.

Total Synthesis and in Vitro Anti-Tumor-Promoting Activities of Racemic Acetophenone Monomers from Acronychia trifoliolata.

Six acetophenone derivatives, acronyculatins I (1), J (2), K (3), L (4), N (5), and O (6), were recently isolated from Acronychia trifoliolata, and the structure of the known acronyculatin B (7) was revised. Because of the limited quantities of isolated products as well as their structure similarity, racemic acronyculatins I-L, N, O, and B (1-7) were synthesized to confirm their structures and to obtain sufficient material for biological evaluation. Trihydroxyacetophenone was converted to the target compounds by various sequences of hydroxy group protection, allylation or prenylation, and epoxidation followed by cyclization. C-Prenylations were carried out by direct addition of a prenyl group or through 1,3- or 3,3-sigmatropic rearrangement. The synthesized racemic compounds were evaluated in an anti-tumor-promoting assay using the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All tested compounds significantly inhibited EBV-EA activation. Especially, racemic acronyculatin I (1) displayed the most potent inhibitory effects, with an IC50 value of 7.3 µM.

Acetophenone Monomers from Acronychia trifoliolata.

Seven new [acronyculatins I-O (1-7)] and four known acetophenone monomers were isolated from a CH3OH/CH2Cl2 (1:1) extract (N089419) of Acronychia trifoliolata provided by the U.S. National Cancer Institute (NCI, Frederick, MD, USA). Their structures were characterized by using various NMR and HRMS techniques. Among the known compounds, the structure of acronyculatin B (8) was revised. Some of the isolated compounds were evaluated for antiproliferative activity against human cancer cell lines. While most of the tested compounds were not cytotoxic, acronyculatins I (1) and J (2) showed moderate antiproliferative activity.

Predictors of Dropout by Female Obese Patients Treated with a Group Cognitive Behavioral Therapy to Promote Weight Loss.

OBJECTIVE: To investigate predictors of dropout from a group cognitive behavioral therapy (CBT) intervention for overweight or obese women. METHODS: 119 overweight and obese Japanese women aged 25-65 years who attended an outpatient weight loss intervention were followed throughout the 7-month weight loss phase. Somatic characteristics, socioeconomic status, obesity-related diseases, diet and exercise habits, and psychological variables (depression, anxiety, self-esteem, alexithymia, parenting style, perfectionism, and eating attitude) were assessed at baseline. Significant variables, extracted by univariate statistical analysis, were then used as independent variables in a stepwise multiple logistic regression analysis with dropout as the dependent variable. RESULTS: 90 participants completed the weight loss phase, giving a dropout rate of 24.4%. The multiple logistic regression analysis demonstrated that compared to completers the dropouts had significantly stronger body shape concern, tended to not have jobs, perceived their mothers to be less caring, and were more disorganized in temperament. Of all these factors, the best predictor of dropout was shape concern. CONCLUSION: Shape concern, job condition, parenting care, and organization predicted dropout from the group CBT weight loss intervention for overweight or obese Japanese women.

Gut Dysbiosis in Patients with Anorexia Nervosa.

Anorexia nervosa (AN) is a psychological illness with devastating physical consequences; however, its pathophysiological mechanism remains unclear. Because numerous reports have indicated the importance of gut microbiota in the regulation of weight gain, it is reasonable to speculate that AN patients might have a microbial imbalance, i.e. dysbiosis, in their gut. In this study, we compared the fecal microbiota of female patients with AN (n = 25), including restrictive (ANR, n = 14) and binge-eating (ANBP, n = 11) subtypes, with those of age-matched healthy female controls (n = 21) using the Yakult Intestinal Flora-SCAN based on 16S or 23S rRNA-targeted RT-quantitative PCR technology. AN patients had significantly lower amounts of total bacteria and obligate anaerobes including those from the Clostridium coccoides group, Clostridium leptum subgroup, and Bacteroides fragilis group than the age-matched healthy women. Lower numbers of Streptococcus were also found in the AN group than in the control group. In the analysis based on AN subtypes, the counts of the Bacteroides fragilis group in the ANR and ANBP groups and the counts of the Clostridium coccoides group in the ANR group were significantly lower than those in the control group. The detection rate of the Lactobacillus plantarum subgroup was significantly lower in the AN group than in the control group. The AN group had significantly lower acetic and propionic acid concentrations in the feces than the control group. Moreover, the subtype analysis showed that the fecal concentrations of acetic acid were lower in the ANR group than in the control group. Principal component analysis confirmed a clear difference in the bacterial components between the AN patients and healthy women. Collectively, these results clearly indicate the existence of dysbiosis in the gut of AN patients.

Three cases of appendicitis with anorexia nervosa under inpatient care.

BACKGROUND: Little is known about the occurrence of appendicitis during the re-nourishment period in anorexia nervosa (AN). We report three cases of appendicitis in patients with AN that occurred after hospitalization for treatment of AN. CASE PRESENTATION: Case 1 is a 34-year-old female, case 2 is a 17-year-old female and case 3 is a 38-year-old female. Constipation was observed in all three cases. Careful management of defecation might be essential to prevent appendicitis among AN patients during the re-nourishment period under inpatient care. In addition, mild and diffuse symptoms were observed in all three cases. Therefore, diagnosis proved to be difficult to make and abdominal computed tomography was particularly helpful in all cases. As the symptoms were diffuse, the condition of appendicitis turned out to be more severe and complicated in one case. Additionally, the incidence of appendicitis in AN in the current study might be higher than that in the normal population. CONCLUSIONS: These findings suggest that appendicitis should be considered as one of the potentially important complications in the therapy for AN.

Clinical significance of the laparoscopic bariatric surgeries for morbid obesity: initial 30 cases at a single institution in Japan.

BACKGROUND: Bariatric surgical procedures are becoming a standard treatment for morbid obesity in many western countries and in some Asian countries. AIM: The aim of the current study was to evaluate the efficacy and safety of the initial 30 cases of bariatric surgical procedures performed for morbid obesity at a single institution in Japan. MATERIALS AND METHODS: From March 2012 until September 2014, 30 bariatric surgical procedures were performed for morbid obesity at a single medical center (Kyushu University Hospital) in Japan. RESULTS: All of the operations procedures were planned laparoscopic procedures, and none required conversion to laparotomy. There were no perioperative or postoperative mortalities. Postoperative complications occurred in 3 patients: 1 patient developed an intra-abdominal abscess, 1 patient experienced temporary food intolerance, and 1 patient developed small bowel obstruction. The excessive body weight reduction rates after surgery at 1 month, 3 months, 6 months, and 1 year post-surgery were 26.1%, 39.2%, 41.7%, and 51.2%, respectively. The mean body mass index (BMI) at the same time points were 38.3%, 36.4%, 35.5%, and 31.4%, respectively. Eighteen patients had type II diabetes mellitus (T2DM). The mean preoperative fasting blood glucose levels were 169 ± 37 mg/dL. Following surgery, the blood glucose levels at 3, 6 and 12 months were 113 ± 12, 115 ± 22, and 110 ± 19, mg/dL, respectively. The preoperative HbA1c percentage was 7.9 ± 0.5. Following surgery, the HbA1c percentages at 3, 6, and 12 months were 6.9 ± 0.5, 6.2 ± 0.9, and 5.9 ± 0.6, respectively. CONCLUSIONS: Bariatric surgical procedures are effective and safe for the treatment of morbid obesity. Our results indicate that the mechanism of improvement of diabetes and related diseases following bariatric surgical procedures is not simply as a result of calorie restriction and weight reduction.

Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population.

The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653-0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557-0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

The longitudinal BMI pattern and body composition of patients with anorexia nervosa who require urgent hospitalization: A case control study.

BACKGROUND: The prevention of serious physical complications in anorexia nervosa (AN) patients is important. The purpose of this study is to clarify which physical and social factors are related to the necessity for urgent hospitalization of anorexia nervosa (AN) patients in a long-term starvation state. We hypothesized that the change of longitudinal BMI, body composition and social background would be useful as an index of the necessity for urgent hospitalization. METHODS: AN patients were classified into; urgent hospitalization, due to disturbance of consciousness or difficulty walking(n = 17); planned admission (n = 96); and outpatient treatment only groups (n = 136). The longitudinal BMI pattern and the clinical features of these groups were examined. In the hospitalization groups, comparison was done of body composition variation and the social background, including the educational level and advice from family members. RESULTS: After adjusting for age and duration of illness, the BMI of the urgent hospitalization group was lower than that of the other groups at one year before hospitalization (P < 0.01) and decreased more rapidly (P < 0.01). Urgent hospitalization was associated with the fat free mass (FFM) (P < 0.01). Between the groups, no considerable difference in social factors was found. CONCLUSIONS: The longitudinal pattern of BMI and FFM may be useful for understanding the severity in AN from the viewpoint of failure of the homeostasis system.

The relationship between the age of onset of type 1 diabetes and the subsequent development of a severe eating disorder by female patients.

OBJECTIVES: To determine the age of onset of type 1 diabetes that is most closely related to the subsequent development of a severe eating disorder such as anorexia nervosa (AN) or bulimia nervosa (BN). METHODS: Participants were 53 female type 1 diabetes patients with AN or BN referred to our outpatient clinic from the Diabetes Center of Tokyo Women's Medical University. Forty-nine female type 1 diabetes patients who regularly visited the Diabetes Center and had no eating disorder-related problems constituted the 'direct control' group, whereas 941 female patients who for the first time visited the Diabetes Center constituted the 'historical control' group. The kernel function method was used to generate a density estimation of the onset age of each group and the chi-square test was used to compare the distribution. RESULTS: The control groups had similar density shapes for the onset age of type 1 diabetes, but both differed from the 'eating disorder' group. For onset age 7-18 yr, the density of the 'eating disorder' group was higher than those of the control groups, but for the younger and older onset ages the densities were lower. The 'eating disorder' group developed type 1 diabetes significantly more frequently than the 'historical control' group between 7 and 18 yr of age (χ2 = 9.066, p < 0.011). CONCLUSION: The development of type 1 diabetes in preadolescence or adolescence seems to place girls at risk for the subsequent development of AN or BN. Careful attention should be paid to these high-risk patients.

BMI, body composition, and the energy requirement for body weight gain in patients with anorexia nervosa.

OBJECTIVE: Theories abound about the energy requirements for body weight gain in anorexia nervosa (AN). We hypothesized that malnutrition status affects the energy requirements. METHOD: On admission, 97 AN patients were measured for body composition by dual-energy X-ray absorptiometry. The relationship between body mass index (BMI) and body composition was investigated. In addition, 21 patients who completed our treatment program were tested for energy intake and body weight. RESULTS: The relationship between BMI and both fat-free mass and fat mass (FM) on admission was curvilinear. The weight gain per excess energy was greater in the group of patients with FM < 4 kg or BMI < 14 kg/m(2) than in the group with FM > or = 4 kg or BMI > or = 14 kg/m(2) (p = .037, p = .055, respectively). DISCUSSION: The energy requirements for weight gain in AN patients are related to the initial FM and BMI.

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: a cross-sectional and prospective study.

BACKGROUND: This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes. METHODS: Participants were 304 patients with type 2 diabetes who were treated as outpatients at diabetes clinics. All participants were assessed for HbA1c and completed the following self-report psychological inventories: 1) Diabetes Treatment Satisfaction Questionnaire (DTSQ), 2) Problem Areas in Diabetes Survey (PAID), 3) Well-being Questionnaire 12 (W-BQ12), 4) Self-Esteem Scale (SES), 5) Social Support Scale, and 6) Self-Efficacy Scale. HbA1c was again measured one year later. The relationships between the psychosocial variables obtained by analysis of the psychological inventories and baseline or one-year follow-up HbA1c were determined. RESULTS: Baseline HbA1cwas significantly correlated with age, diet treatment regimen, number of microvascular complication of diabetes, and the total scores of DTSQ, W-BQ12, PAID, SES and the Self-Efficacy Scale. Hierarchical stepwise multiple regression revealed that significant predictors of baseline HbA1c were total DTSQ and PAID scores, along with age, diet treatment regimen, and number of microvascular complication of diabetes after adjustment for demographic, clinical and other psychosocial variables. Two hundred and ninety patients (95.4% of 304) were followed and assessed one year after baseline. Hierarchical stepwise multiple regression analysis showed the significant predictors of follow-up HbA1c to be total DTSQ and PAID scores, along with age and diet treatment regimen. However, the correlation between baseline and follow-up HbA1c was so high that the only other variable to retain significance was diet treatment regimen once baseline HbA1c was included in the regression of follow-up HbA1c. CONCLUSION: The DTSQ and the PAID predicted both current and future HbA1c to a similar and significant degree in patients with type 2 diabetes.

Psychopathological features of anorectic patients who dropped out of inpatient treatment as assessed by the Minnesota multiphasic personality inventory.

BACKGROUND: Anorexia nervosa often requires inpatient treatment that includes psychotherapeutic intervention in addition to physical and nutritional management for severe low body weight. However, such patients sometimes terminate inpatient treatment prematurely because of resistance to treatment, poor motivation for treatment, unstable emotions, and problematic behaviors. In this study, the psychopathological factors related to the personality of anorexic patients that might predict discontinuation of inpatient treatment were investigated using the Minnesota Multiphasic Personality Inventory (MMPI). METHODS: Subjects were 75 consecutive anorectic inpatients who received cognitive behavioral therapy with a behavior protocol governing privileges in a university hospital based general (not psychiatric) ward. The MMPI was done on admission for all patients. A comparison was done of patients who completed the process of inpatient treatment, including attainment of target body weight (completers), and patients who dropped out of inpatient treatment (dropouts). RESULTS: No significant differences between completers (n = 51) and dropouts (n = 24) were found in the type of eating disorder, age of onset, duration of illness, age, or BMI at admission. Logistic regression analysis found the MMPI scales schizophrenia (Sc), hypomania (HYP), deviant thinking and experience, and antisocial attitude to be factors predicting completion or dropout. CONCLUSION: Dropouts have difficulty adapting to inpatient treatment protocols such as our behavior protocol governing privileges because they have social and emotional alienation, a lack of ego mastery (Sc), emotional instability (HYP) and an antisocial attitude. As a result, they have decreased motivation for treatment, leave the hospital without permission, attempt suicide, or shoplift, which leads them to terminate inpatient treatment prematurely. Treatments based on cognitive behavioral therapy with a behavior protocol governing privileges should be carefully adopted for anorectic patients who exhibit the psychopathological elements identified in this study.