Behavioral activation for depression in patients with advanced cancer: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Though behavioral activation (BA) has been shown to be effective for depression, evidence in patients with advanced cancer has not been established. This study aimed to examine the effectiveness of a BA program on depression in this population. METHODS: A randomized controlled trial with a wait-list control group (waiting group) of 38 patients with advanced cancer and depression will be conducted at three sites in Japan. The BA program consists of seven sessions. Outcome measures will be evaluated at three times in the intervention group; at the entry, at the end of the intervention and 4 months after the end of the intervention and four times in the waiting group: at the entry, before the intervention, at the end of the intervention, and 4 months after the end of the intervention. Primary outcome is Beck Depression Inventory-II (BDI-II) score. To examine the main effect of the intervention, two-way repeated measures analysis of variance (ANOVA) will be conducted, with timing and intervention status as the independent variables and BDI-II score as the dependent variable. One-way repeated measures ANOVA will be conducted to combine data from the intervention and control groups and examine changes in BDI-II scores by timing in both groups. Secondary endpoints (anxiety, quality of life, spirituality, degree of behavioral activation, value, and pain) will be evaluated with rating scales. Two-way repeated measures ANOVA will be conducted to examine whether there are differences between the groups before and after the intervention, with timing and intervention status as the independent variables and scores on each rating scale as the dependent variables. DISCUSSION: This multicenter randomized controlled trial is the first study to assess the effectiveness of BA on depression in patients with advanced cancer. Our findings will provide evidence about the effectiveness of BA on depression and provide an intervention option that is acceptable and feasible for the treatment of depression in this population. The results of this study will lead to improved mood and rebuilding to regain life purpose and value in this vulnerable population. TRIAL REGISTRATION NUMBER: jRCT, jRCT1030210687, Registered 22 March 2022, https://jrct.niph.go.jp/en-latest-detail/jRCT1030210687 .

The mediating effect of activity restriction on the relationship between perceived physical symptoms and depression in cancer survivors.

PURPOSE: Several studies have explored factors causing depression in cancer survivors, including perceived physical symptoms. Another critical factor in the depression symptomatology of cancer survivors is activity restriction (AR). We investigated how AR mediate the effects of perceived pain and fatigue on depression in cancer survivors. METHODS: Cancer survivors (n = 61; mean age 56.16 years) that were recruited through cancer support groups in Japan participated in this study. Participants completed a battery of questionnaires comprising demographic and clinical information, the Pain Catastrophizing Scale, the Cancer Fatigue Scale, the Activity Restriction Scale for Cancer Patients, and the Hospital Anxiety and Depression Scale. RESULTS: Mediation analysis indicated that AR partially mediates the effect of pain on depression. Direct paths from pain to AR, AR to depression, and pain to depression were significant (P < .005). Moreover, indirect paths from pain to AR, AR to depression, and pain to depression were also significant at the 95% level [0.04-0.13]. However, AR did not mediate the effect of fatigue on depression, and fatigue had a significant direct path to both AR and depression (P < .005). CONCLUSION: This study aimed to explore the mediating effect of AR in the relationships of perceived pain and fatigue and depression in cancer survivors. We found that AR mediates perceived pain to depression, however not for perceived fatigue. In addition, because AR was experienced in the face of any survivorship period, AR may need to be treated as a long-term effect of the cancer diagnosis.

Psychosocial difficulties in adolescent and young adult survivors of childhood cancer.

BACKGROUND: With a large number of children surviving cancer worldwide, numerous investigations have assessed psychological and social adjustment among childhood cancer survivors. According to these studies, it is unclear whether childhood cancer survivors successfully adjust to daily life after being discharged from hospital, especially for adolescent and young adult survivors who have unique needs and concerns. The primary aim of this study was to identify the factors underlying psychosocial difficulties faced by adolescent and young adult survivors in their day-to-day lives after being discharged from hospital. METHODS: Semi-structured interviews were conducted. Twenty-five childhood cancer survivors were recruited from two regional cancer institutions in Japan. Content analysis was applied to the responses. RESULTS: Nineteen attributes were extracted and classified into four categories as follows: physical difficulties, interpersonal difficulties, behavioral difficulties, and uncertainty about the future. The attributes indicated by >50% of the participants were "I am worried about not feeling well," "I have difficulty continuing treatment in daily life," "I have difficulty moving my body," "I have to be absent from school or work because of illness," and "I am left behind academically." CONCLUSIONS: This study identified important factors of psychosocial day-to-day difficulties. Clinically, these results suggest that it is important to watch for these signs and to provide early support to survivors so that their daily life and development are not hindered by the treatment and its side-effects, and to offer long-term support focusing on individual patient characteristics such as sex, age, and cancer history.

Feasibility and Preliminary Effectiveness of Behavioral Activation for Patients with Cancer and Depression in Japan.

Background: Though the effectiveness of behavioral activation (BA) for patients with cancer and depression were reported, there is no evidence in Japan. Objectives: This study aimed at examining the feasibility and preliminary effectiveness of BA for patients with cancer and depression in Japan. Methods: This pre-post study without a control group was conducted in patients with cancer and depression in Japan. The program completion rate was compared with those of previous studies to examine feasibility. To examine the preliminary effectiveness, outcomes were evaluated four times: before and immediately after the program, and two weeks and three months after the program ended. The primary outcome was the remission rate of depression using the 17-item version of the GRID Hamilton Rating Scale for Depression (HAMD17). Secondary outcomes were self-reported depression, anxiety, quality of life, changes in behavior, values, and perceived reward of activity and environmental factors. Pre- and post-program data were compared using paired-samples t-tests, and data obtained at four time points were analyzed using one-way repeated-measures analysis of variance. Results: Of the 68 patients recruited from February 2018 to January 2022, 32 were registered. The completion rate was 75% (24/32), which was similar to previous studies. The total HAMD17 score significantly improved after the program. The remission rate of depression was 62.5% (20/32), which was above the defined threshold value (30%). All but two secondary outcomes significantly improved after the program (p < 0.05). Conclusions: The feasibility and preliminary effectiveness of BA for patients with cancer and depression in Japan were suggested.The Clinical Trial Registration number: UMIN 000036104.

Delay in the diagnosis of multiple endocrine neoplasia type 1: typical symptoms are frequently overlooked.

The morbidity and mortality of individuals with multiple endocrine neoplasia type 1 (MEN1) can be reduced by early diagnosis of MEN1 and related endocrine tumors. To find factors contributing to early diagnosis, we collected clinical information on MEN1 patients through a MEN study group, "MEN Consortium of Japan" and analyzed the time of initial symptom-dependent detection of parathyroid tumors, gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) and pituitary tumors, and that of tumor detection-dependent MEN1 diagnosis in 560 patients. Main tumors were identified up to 7.0 years after symptoms appeared and there was no difference in age at the diagnosis of GEPNETs alone between probands and family members. In patients with typical symptoms (peptic ulcers, urolithiasis, fasting hypoglycemia, bone fracture/loss and amenorrhea), the mean interval between symptom manifestation and tumor detection was extended up to 9.6 years. In particular, 21.7% (5/23) of patients with amenorrhea were diagnosed with pituitary tumors in under one year. In patients with peptic ulcers (from parathyroid tumors or GEPNETs) and urolithiasis (from parathyroid tumors), the interval was positively correlated with age at tumor detection. The interval between tumor detection and MEN1 diagnosis was also prolonged to approximately four years in patients with fasting hypoglycemia (from GEPNETs) and amenorrhea. A substantial delay in the diagnosis of symptom-related tumors and subsequent MEN1 and inadequate screening of GEPNETs in family members were indicated. A greater understanding of MEN1 may assist medical practitioners to make earlier diagnoses, to share patients' medical information and to give family members sufficient disease information.

[A case of carcinoma associated with anal fistula resected after preoperative chemoradiotherapy].

A 66-year-old man with a 39-year history of anal fistula was admitted to our hospital for anal pain and bleeding. Fistulectomy was carried out for anal fistula. Histological examination of the specimen revealed carcinoma associated with anal fistula. A computed tomography showed that the tumor had invaded the prostate. Therefore, preoperative chemoradiotherapy(S-1 plus radiation 40 Gy/body)for locally advanced cancer was performed. Magnetic resonance imaging showed that the boundary between the tumor and the prostate was unclear, but we performed an abdominoperineal resection and the prostate was fully preserved. Histopathologically, no cancer cell existed on the surgical margin. The histological effect of chemoradiotherapy was judged as grade 2. This case suggested that surgical treatment combined with preoperative chemoradiotherapy may be effective for locally advanced carcinoma associated with anal fistula, in which preservation of adjacent organs is considered to be difficult.

Psychosocial functioning in patients with Treatment-Resistant Depression after group cognitive behavioral therapy.

BACKGROUND: Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year. METHODS: Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up. RESULTS: Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT. CONCLUSIONS: These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.

Investigation of thyroid cancer cases that were not detected in the Thyroid Ultrasound Examination program of the Fukushima Health Management Survey but diagnosed at Fukushima Medical University Hospital.

The Great East Japan Earthquake, which occurred on March 11, 2011, and its subsequent Fukushima Daiichi Nuclear Power Plant accident, prompted implementation of the Thyroid Ultrasound Examination (TUE) program as a part of the Fukushima Health Management Survey. The purpose of this program is to support residents of Fukushima Prefecture, and to analyze the health effects of the released radionuclides. Regardless of relatively high participation rates and a well-planned diagnostic flow, it is conceivable that not all thyroid cancer cases can be detected by the TUE program. The aims of the present study were to identify and characterize these "outside" cases, targeting patients at Fukushima Medical University (FMU) Hospital. As of June 30, 2017, we have successfully identified 11 outside cases. These corresponded to 5.7% of the 194 subjects who were identified as having thyroid cancer or suspected thyroid cancer in the TUE program. Although the outside subjects of other institutes were not investigated, the present study may have identified the majority of outside subjects in Japan, considering that FMU Hospital treats a large number of thyroid cancer subjects. Furthermore, the characteristics of the 11 subjects were not different from those of the subjects identified in the TUE program. These findings confirm that the TUE program was able to identify subjects of thyroid cancer adequately and sufficiently.

Self-referential processing of negative stimuli within the ventral anterior cingulate gyrus and right amygdala.

Neural activity associated with self-referential processing of emotional stimuli was investigated using whole brain functional magnetic resonance imaging (fMRI). Fifteen healthy subjects underwent fMRI scanning while making judgments about positive and negative trait words in four conditions (self-reference, other-reference, semantic processing, and letter processing). Significant activity was observed in the right ventral anterior cingulate gyrus and the right amygdala in the negative-word/self-reference condition, and in the left amygdala in the positive-word/self-reference condition. Compared with the semantic-processing condition, the self-reference conditions showed significantly more activity in the medial prefrontal and temporal gyri, posterior cingulate gyrus, and precuneus. These results suggest that the medial prefrontal gyrus, posterior cingulate gyrus, and precuneus are associated with a self-referential processing, and the ventral anterior cingulate gyrus is involved in self-referential processing of negative emotional stimuli. The results also suggest that the amygdala is associated with self-referential processing of both positive and negative emotional stimuli.

Interaction Effects of Behavioral Inhibition System/Behavioral Activation System and Cost/Probability Biases on Social Anxiety.

INTRODUCTION: Social anxiety disorder (SAD) symptoms are maintained by cognitive biases, which are overestimations of the severity and likelihood of negative social events (cost/probability biases), and by sensitivity to rewards and punishments that are determined according to behavioral inhibition/behavioral activation systems (BIS/BAS). Cost/probability biases might activate the behavioral immune system and exacerbate the avoidance of social events. Earlier studies have proposed that low BIS or high BAS decrease SAD symptoms; BIS/BAS may even change the effects of cognitive biases on SAD symptoms. Hence, the current study investigates the interaction effects of BIS/BAS and cost/probability biases on SAD symptoms. METHOD: Seventy-six Japanese undergraduate students completed the Japanese version of the Liebowitz Social Anxiety Scale (LSAS), which comprises Fear and Avoidance subscales, the BIS/BAS Scale, and the Social Cost Probability Scale. RESULTS: A multiple regression analysis was performed to examine whether cost/probability biases, BIS/BAS, and their interactions affected SAD symptoms; following this, the main effects of cost bias and BIS were determined for LSAS-Fear (ß = 0.64, p < 0.001; ß = 0.33, p < 0.01) and LSAS-Avoidance (ß = 0.49, p < 0.001; ß = 0.35, p < 0.01). The interaction effect between cost bias and BAS was significant for LSAS-Avoidance (ß = -0.32, p < 0.05). Simple slope analysis showed that the slope of cost bias was significant for low-BAS individuals (ß = 0.77, p < 0.001) but not for high-BAS individuals (ß = -0.21, n.s.). The interaction effect between probability bias and BAS was significant for LSAS-Avoidance (ß = 0.40, p < 0.01) as well. Further, simple slope analysis revealed that the slope of probability bias was significant for low-BAS individuals (ß = -0.53, p < 0.05) but not for high-BAS individuals (ß = 0.17, n.s.). DISCUSSION: The study found interesting results with respect to the avoidance of social events. Low-BAS individuals with high cost or low probability biases regarding social events may have a tendency to avoid social events. In contrast, if high-BAS individuals overestimate the cost of social events or underestimate the probability of social events, their anticipation of rewards might prevent them from avoiding social events.

Behavioral activation therapy for depression and anxiety in cancer patients: a case series study.

BACKGROUND: Behavioral activation therapy (BAT) directly addresses activities that individuals value most highly, and may be easily applicable to cancer patients. However, there is no established evidence of the use of BAT in this population. In this study, we examined the possibility of a BAT program for depression and anxiety in cancer patients. CASE PRESENTATION: We retrospectively reviewed the medical records of cancer patients with each of the following characteristics: 1) were outpatients or inpatients visiting the psycho-oncology division of the National Cancer Center Hospital in Japan; 2) met criteria for Major Depressive Disorder or Adjustment Disorders; and 3) participated in a BAT program. The primary outcome was the program completion percentage. Secondary outcomes were self-reported depression severity (Patient Health Questionnaire-9 (PHQ-9) score), anxiety disorder status (Generalized Anxiety Disorder-7 (GAD-7) score), and clinical improvement (Clinical Global Impression-Improvement (CGI-I) score) after the program. We analyzed both depression and anxiety by the matched paired t-test. Ten patients participated in the program, and nine completed it. One dropped out due to cognitive impairment secondary to brain metastasis. Both the PHQ-9 scores (pre: 14.4 (SD, 6.1); post: 5.1 (SD, 5.8)) and the GAD-7 scores (pre: 11.9 (SD, 4.9); post: 4.7 (SD, 5.5)) significantly improved after the program (PHQ-9: P = 0.0014; GAD-7: P = 0.0004). CGI-I scores ranged from 1 to 3, and all subjects except the patient who dropped out improved clinically. Among the ten patients, three distinctive cases could be observed as follows. Case 1; a 45-year-old housewife with breast cancer who did not agree to take antidepressants because of concerns about the side effects achieved remission without antidepressants and began to live an active life. Case 4; a 66-year-old housewife was so shocked after endometrial cancer diagnosis that she was absent-minded and her compliance with the assigned homework was poor, therefore, her depression did not improve much. Case 9; a 62-year-old man with laryngeal cancer who had recurrent anxiety. Increased business activity, on which he put great value, gradually allowed him to be able to live his life actively without concerns. CONCLUSIONS: This study suggests that BAT would be effective for the depression and anxiety of cancer patients.

Incidence of Thyroid Cancer Among Children and Young Adults in Fukushima, Japan, Screened With 2 Rounds of Ultrasonography Within 5 Years of the 2011 Fukushima Daiichi Nuclear Power Station Accident.

Importance: Ultrasonographic (US) screening for thyroid cancer was performed in the Fukushima Health Management Survey after the 2011 Fukushima Daiichi nuclear power station accident. Clinical characteristics of thyroid cancers screened by US among children and young adults during the first 5 years after the accident were analyzed. Objectives: To evaluate the number of detected thyroid cancers by age group within 5 years of the Fukushima Daiichi nuclear power station accident and to compare the basic clinical characteristics and demographic patterns in first- and second-round examinations. Design, Setting, and Participants: In this observational study, 324 301 individuals 18 years or younger at the time of accident were included. Patients received a cytologic diagnosis of malignant or suspected malignant thyroid cancer during the first (fiscal years 2011-2013) or second round (fiscal years 2014-2015) of screening. Number of detected cases of cancer was evaluated, correcting for the number of examinees by age group at the time of the accident and for the incidence of detected cancers according to age group at the time of the screening (age groups were divided into 3-year intervals). Results were compared using the age-specific incidence of unscreened cancers from a national cancer registry. Main Outcomes and Measures: Clinical baseline characteristics of the patients and the age-specific number and incidence of thyroid cancers detected during the second round. Results: Among 299 905 individuals screened in the first round (50.5% male; mean [SD] age at screening, 14.9 [2.6] years), malignant or suspected thyroid cancer was diagnosed in 116. Among 271 083 individuals screened in the second round (50.4% male; age at screening, 12.6 [3.2] years), malignant or suspected thyroid cancer was diagnosed in 71. The most common pathologic diagnosis in surgical cases was papillary thyroid cancer (149 of 152 [98.0%]). The distribution pattern by age group at the time of the accident, where the number of detected thyroid cancer cases was corrected by the number of examinees, increased with older age in both screening rounds. This demographic pattern was similar between the first and second examinations. The distribution pattern of the incidence rate by age group at the time of screening in the second round also increased with older age. The incidence rate detected by screening was 29 cases per 100 000 person-years for those aged 15 to 17 years, 48 cases per 100 000 person-years for those aged 18 to 20 years, and 64 cases per 100 000 person-years for those aged 21 to 22 years. Conclusions and Relevance: Large-scale mass US screening of young people resulted in the diagnosis of a number of thyroid cancers, with no major changes in overall characteristics within 5 years of the 2011 Fukushima nuclear power station accident. These results suggest that US screening can identify many detectable cancers from a large pool of nonclinical and subclinical thyroid cancers among individuals of a relatively young age, in an age-dependent manner.

Characterization of the catalytic activity of the gamma-phage lysin, PlyG, specific for Bacillus anthracis.

Bacillus anthracis causes anthrax, a lethal disease affecting humans that has attracted attention due to its bioterrorism potential. PlyG is a lysin of gamma-phage, which specifically infects B. anthracis and lyses its cell wall. PlyG contains a T7 lysozyme-like amidase domain, which appears to be the catalytic domain, in the N-terminal region and has a high degree of sequence similarity with PlyL, which is an N-acetylmuramoyl-l-alanine amidase encoded by the B. anthracis genome. Here, we demonstrated that two amino acid residues of PlyG, H29 and E90, are necessary for its catalytic activity in B. anthracis. These residues are structurally analogous to residues whose mutation in T7 lysozyme abolished its catalytic activity. A C-terminal deletion mutant of PlyG lacking the core sequence for binding to B. anthracis showed completely abolished binding activity, unlike PlyL, despite high sequence similarity with PlyL in the N-terminal region. This suggests that the C-terminal binding domain, as well as the N-terminal catalytic domain, is essential for the catalytic activity of PlyG. Our observations provide new insights into the mechanism of specific catalysis of PlyG in B. anthracis and may contribute to the establishment of new methods for anthrax therapy.

Subcritical water extraction of barley to produce a functional drink.

We investigated the effects of various temperatures between 150 and 280 degrees C during subcritical water extraction of barley to make a barley tea-like extract, a popular summer beverage in Japan. Each barley extract was analyzed for sensory properties, antioxidative activity, and the amount of residual matter, which revealed 205 degrees C to be the best extraction parameter. 5-Hydroxymethyl-2-furaldehyde was found to be the major antioxidative component in the 205 degrees C extract, along with the formation of several important amino acids.

Comparative Analysis of the Growth Pattern of Thyroid Cancer in Young Patients Screened by Ultrasonography in Japan After a Nuclear Accident: The Fukushima Health Management Survey.

IMPORTANCE: Thyroid cancer generally grows at a very slow rate in adults, and overdiagnosis is a global issue. However, the detection of early-stage thyroid cancer by screening is not well described in young patients. To prevent overdiagnosis, it is essential to understand the natural course of thyroid cancer growth detection by ultrasonography screening in young patients. OBJECTIVE: To evaluate the natural progression of thyroid cancer in young patients. DESIGN, SETTING, AND PARTICIPANTS: An observational study evaluated changes in the diameter of malignant or suspected malignant thyroid tumors on 2 occasions. Changes in malignant thyroid tumor diameter were estimated during the observation period between the screening and confirmatory examinations in the first-round thyroid ultrasonography examination of the Fukushima Health Management Survey in patients younger than 21 years after a nuclear accident at a power plant in Fukushima, Japan. In total, 116 patients cytologically diagnosed with or suspected to have thyroid cancer were classified into 3 groups based on a greater than 10% reduction, a change of -10% to +10% in diameter, and a greater than 10% increase in tumor diameter. The association between tumor growth rate and tumor diameter was analyzed. The study was conducted from March 1, 2016, to August 6, 2017. MAIN OUTCOMES AND MEASURES: Tumor volume changes, the coefficient of growth of thyroid cancer in young patients, and the association between the observation period or tumor diameter and them. RESULTS: Of 116 patients, 77 were female; the mean age was 16.9 years (median, 17.5 years). The mean observation period was 0.488 (range, 0.077-1.632) years. No significant differences in age, sex, tumor diameter, observation period, or serum levels of thyrotropin and thyroglobulin were observed among the groups. Whereas tumor volume changes were not linearly correlated with the observation period (Pearson R = 0.121; 95% CI, -0.062 to 0.297), the coefficient of growth was significantly and negatively correlated with the tumor diameter in the screening examination (Spearman ρ = -0.183; 95% CI, -0.354 to -0.001), suggesting growth arrest after the initial proliferation phase. CONCLUSIONS AND RELEVANCE: Ultrasonography screening could reveal asymptomatic thyroid cancer that is falling into a growth arrest pattern in many young patients. Considering the long life expectancy, prevention of overdiagnosis necessitates careful long-term monitoring without immediate diagnosis for suspected noninvasive thyroid cancer.

Trierixin, a novel Inhibitor of ER stress-induced XBP1 activation from Streptomyces sp. 1. Taxonomy, fermentation, isolation and biological activities.

In the course of screening for an inhibitor of ER stress-induced XBP1 activation, we isolated a new member of the triene-ansamycin group compound, trierixin, from a culture broth of Streptomyces sp. AC 654. Trierixin was purified by column chromatography on silica gel and by HPLC. The molecular formula of trierixin is C(37)H(52)N(2)O(8)S. Trierixin inhibited thapsigargin-induced XBP1-luciferase activation in HeLa/XBP1-luc cells and endogenous XBP1 splicing in HeLa cells with an IC(50) of 14 ng/ml and 19 ng/ml, respectively. Moreover, in the process of isolating trierixin, we isolated structurally related mycotrienin II and trienomycin A as inhibitors of ER stress-induced XBP1 activation from a culture broth of a trierixin-producing strain. This study provides the first observation that triene-ansamycins have a novel inhibitory effect against XBP1 activation.

Skin dose measurement for patients using imaging plates in interventional radiology procedures.

A method using europium-doped BaFBr imaging plates (IPs) has been developed to estimate and map values of entrance skin doses during interventional radiology (IR). IPs offer many advantages for measuring the entrance skin dose because they have a wide dynamic range (up to 100 Gy), provide high spatial resolution as a detector of two-dimensional images, and can be used repeatedly. The entrance skin dose was measured by fitting a 40x40 cm IP sheet around a patient's back using a corset in clinical studies involving IR procedures at two hospitals. The corset can minimize a geometric discrepancy in dose estimates between the IP and the patient body. The entrance skin dose was measured by using photoluminescent glass dosimeters simultaneously, and both values were compared. The spatial relative dose profiles from both dose estimates showed generally good agreement; however, the doses obtained with glass dosimeter chips were often lower than those obtained with IPs. This discrepancy comes from a radiation shielding effect for x rays by IPs and a strong angular dependence of the glass dosimeter in low energy x-ray fields. Comprehensive results of this study demonstrated that IPs were able to measure entrance skin dose in even high dose regions with steep dose gradients and to determine the peak skin dose, without missing hot spots, over all ranges used during interventional radiology procedures. Use of the corset minimized variations associated with angular dependence.

ING2, a tumor associated gene, enhances PAI­1 and HSPA1A expression with HDAC1 and mSin3A through the PHD domain and C­terminal.

Inhibitor of growth 2 (ING2) is involved in chromatin remodeling and it has previously been suggested that ING2 may regulate gene expression. The authors previously identified matrix metalloproteinase 13 (MMP13) as a target gene of ING2 in colorectal cancer. The aim of the present study was to identify novel genes regulated by ING2 and histone deacetylase 1 (HDAC1) and to clarify the biological significance of the ING2 structure. The present study generated the point mutant constructs of ING2 and deletion constructs consisting of partial ING2 to investigate the effect on gene expression and verify the interaction with HDAC1, mSin3A and sap30. A microarray was performed to find novel ING2/HDAC1 target genes using cell co­overexpression of ING2 and HDAC1. Plasminogen activator inhibitor­1 (PAI­1) was upregulated with overexpression of ING1b and ING2. The mutation of the PHD domain at 218 significantly attenuated the MMP13 and PAI­1 expression, whereas the mutation at 224 resulted in increased expression. Furthermore, the expression levels were slightly reduced by the mutation of the C­terminal. The lack of the PHD domain and the C­terminal in ING2 resulted in a decreased ability to induce gene expression. The C­terminal with PHD domain, which lacked the N­terminal, maintained the transactive function for regulating the target genes. In addition to MMP13 and PAI­1, eight genes [heat shock protein family A member 1A (HSPA1A), MIR7­3 host gene, chorionic somatomammotropin hormone 1, growth arrest and DNA damage inducible b, dehydrogenase/reductase 2, galectin 1, myosin light chain 1, and VGF nerve growth factor inducible] were demonstrated to be associated with ING2/HDAC1. The present study demonstrated that ING2/HDAC1 regulated PAI­1 and HSPA1A expression and the PHD domain and the C­terminal of ING2, which are binding sites of HDAC1 and mSin3A, are essential regions for the regulation of gene expression.

Avoidance behavior associated with depressive symptoms in patients with implantable cardioverter defibrillators.

Objective: Many patients with implantable cardioverter defibrillators experience depressive symptoms. In addition, avoidance behavior is a common problem among patients with implantable cardioverter defibrillators. We examined the association between avoidance behaviors and depressive symptoms in patients with implantable cardioverter defibrillators. Method: We conducted a single-center, cross-sectional study with self-completed questionnaires between May 2010 and March 2011. We measured avoidance behaviors (avoidance of places, avoidance of objects, and avoidance of situations) and depressive symptoms (using the Beck Depression Inventory, Version II) in 119 participants. An avoidance behaviors instrument was developed for this study and we confirmed its internal consistency reliability. Results: Ninety-two (77.3%) patients were aged older than 50 years, and 86 (72.3%) were men. Fifty-one (42.9%) patients reported "avoidance of places", 34 (28.6%) reported "avoidance of objects", and 63 (52.9%) reported "avoidance of activity". Avoidance behavior was associated with increased odds for the presence of depressive symptoms (OR 1.31; 95% CI 1.06-1.62). Conclusions: This was the first study to identify the relationship between avoidance behavior and depressive symptoms among patients with implantable cardioverter defibrillators; however, there are a few methodological limitations.

Objetivo: Muchos pacientes con desfibriladores cardioversores implantables experimentan síntomas depresivos. Además, la conducta de evitación es un problema común entre estos pacientes. El objetivo fue examinar la asociación entre las conductas de evitación y síntomas depresivos en pacientes con desfibriladores cardioversores implantables. Método: Se llevó a cabo un estudio transversal en un único centro entre mayo de 2010 y marzo de 2011. Mediante autoinformes se midieron conductas de evitación (evitación a lugares, evitación a objetos y evitación a situaciones) y síntomas depresivos (mediante el Inventario de Depresión de Beck, Versión II) en 119 participantes. El instrumento de evitación se desarrolló para este estudio con adecuada fiabilidad de consistencia interna. Resultados: Noventa y dos pacientes (77,3%) tenían más de 50 años y 86 pacientes (72,3%) eran hombres. Cincuenta y un pacientes (42,9%) informaron de "evitación a lugares", 34 pacientes (28,6%) informaron de "evitación a objetos" y 63 pacientes (52,9%) informaron "evitación a actividad". La conducta de evitación se asoció con un aumento en la probabilidad de síntomas depresivos (OR 1,31; IC del 95%, 1,06-1,62). Conclusiones: Este es el primer estudio para identificar la relación entre la conducta de evitación y síntomas depresivos en pacientes portadores de desfibriladores cardioversores implantables, aunque existen algunas limitaciones metodológicas.

Cognitive behavioral therapy changes functional connectivity between medial prefrontal and anterior cingulate cortices.

BACKGROUND: Depression is characterized by negative self-cognition. Our previous study (Yoshimura et al. 2014) revealed changes in brain activity after cognitive behavioral therapy (CBT) for depression, but changes in functional connectivity were not assessed. METHOD: This study included 29 depressive patients and 15 healthy control participants. Functional Magnetic Resonance Imaging was used to investigate possible CBT-related functional connectivity changes associated with negative emotional self-referential processing. Depressed and healthy participants (overlapping with our previous study, Yoshimura et al. 2014) were included. We defined a seed region (medial prefrontal cortex) and coupled region (ACC) based on our previous study, and we examined changes in MPFC-ACC functional connectivity from pretreatment to posttreatment. RESULTS: CBT was associated with reduced functional connectivity between the MPFC and ACC. Symptom change with CBT was positively correlated with change in MPFC-ACC functional connectivity. LIMITATIONS: Patients received pharmacotherapy including antidepressant. The present sample size was quite small and more study is needed. Statistical threshold in fMRI analysis was relatively liberal. CONCLUSIONS: CBT for depression may disrupt MPFC-ACC connectivity, with associated improvements in depressive symptoms and dysfunctional cognition.