Social operant conditioning of autobiographical memory sharing.

The memories for past autobiographical experiences that we share can influence relationship formation and consolidation with important implications for our mental health. However, little is known about how people's responses to our memories can influence subsequent memory sharing. Previous research examined how operant processes (i.e., punishment with aversive sounds) influence the sharing of memories for specific events from our past. Understanding the (social) mechanisms associated with difficulty sharing specific autobiographical memories is important given the association between these difficulties and a range of psychiatric diagnoses. We investigate the effects of verbal and non-verbal social operants on the willingness to share specific autobiographical memories. Participants shared memories with a confederate who coded their memories as specific or non-specific and responded in either an engaged/attentive, dismissive manner or gave no feedback depending on participants' assigned condition. Participants who were reinforced for sharing specific memories and punished for sharing non-specific memories, were more likely to share specific than non-specific memories compared to those who received no feedback. Reinforcement alone was not sufficient for modifying specificity. The ways that we respond to people when they share memories with us can influence their subsequent willingness to share specific events from their past.

Emotion Regulation as a Mediator in the Relationship Between Cognitive Biases and Depressive Symptoms in Depressed, At-risk and Healthy Children and Adolescents.

Contemporary cognitive models of depression propose that cognitive biases for negative information at the level of attention (attention biases; AB) and interpretation (interpretation biases; IB) increase depression risk by promoting maladaptive emotion regulation (ER). So far, empirical support testing interactions between these variables is restricted to non-clinical and clinical adult samples. The aim of the current study was to extend these findings to a sample of children and adolescents. This cross-sectional study included 109 children aged 9-14 years who completed behavioural measures of AB (passive-viewing task) and IB (scrambled sentences task) as well as self-report measures of ER and depressive symptoms. In order to maximize the variance in these outcomes we included participants with a clinical diagnosis of depression as well as non-depressed youth with an elevated familial risk of depression and non-depressed youth with a low familial risk of depression. Path model analysis indicated that all variables (AB, IB, adaptive and maladaptive ER) had a direct effect on depressive symptoms. IB and AB also had significant indirect effects on depressive symptoms via maladaptive and adaptive ER. These findings provide initial support for the role of ER as a mediator between cognitive biases and depressive symptoms and provide the foundations for future experimental and longitudinal studies. In contrast to studies in adult samples, both adaptive as well as maladaptive ER mediated the effect of cognitive biases on depressive symptoms. This suggests potentially developmental differences in the role of ER across the lifespan.

Computerized Memory Specificity Training (c-MeST) for major depression: A randomised controlled trial.

Given modest response and high relapse after treatment for Major Depressive Episodes (MDE), the development and refinement of treatments to target cognitive vulnerabilities is indicated. Memory Specificity Training (MeST) remediates deficits in recalling detailed memories of past experiences through repeated practice of autobiographical memory retrieval. This randomised controlled trial aimed to assess the efficacy of an online, computerized version of MeST (c-MeST) for MDE. Adults (N = 245, 88.4% female; M age = 46.4) with a current MDE were randomised to the c-MeST program or wait-list control group. Significantly fewer participants in the c-MeST group, relative to control, met criteria for an MDE at one-month follow-up (35.7% c-MeST vs. 60.6% control), but not at other time-points. The c-MeST group, relative to the control group, scored significantly higher on memory specificity at all time-points following baseline (d = 0.53-0.93), and lower on depressive symptoms at one (d = 0.57) and three-month follow-up (d = 0.67). Changes in memory specificity mediated the effect of c-MeST on depressive symptoms at follow-up. c-MeST can improve memory specificity and depressive symptoms in people with an MDE, and may speed the rate of recovery. Future studies can further examine the mechanisms through which this occurs.

A study protocol for a randomised trial of adjunct computerised memory specificity training (c-MeST) for major depression in youth: targeting cognitive mechanisms to enhance usual care outcomes in mental health settings.

BACKGROUND: Youth depression is highly prevalent and is related to impairments in academic, social and behavioural functioning. Evidence-based treatments are available, but many young people do not respond or sufficiently recover with first-line options, and a significant proportion experience relapse. Consequently, there is clear scope to enhance intervention in this critical period of early-onset depression. Memory specificity training (MeST) is a low-intensity intervention for depression that targets reduced specificity when recalling memories of the past, a common cognitive vulnerability in depression. This randomised controlled trial will assess the efficacy of adding a computerised version of MeST (c-MeST) to usual care for youth depression. METHODS/DESIGN: Young people aged 15-25 years with a major depressive episode (MDE) will be recruited and randomised to have immediate access to the seven session online c-MeST program in addition to usual care, or to usual care and wait-list for c-MeST. The primary outcomes will be diagnostic status of an MDE and self-reported depressive symptoms assessed at baseline, 1-, 3- and 6-month intervals. Autobiographical memory specificity and other variables thought to contribute to the maintenance of reduced memory specificity and depression will be assessed as mediators of change. DISCUSSION: Online provision of c-MeST provides a simple, low-intensity option for targeting a cognitive vulnerability that predicts the persistence of depressive symptoms. If found to be efficacious as an adjunct to usual care for depressed youth, it could be suitable for broader roll-out, as c-MeST is highly accessible and implementation requires only minimal resources due to the online and automated nature of intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619000234112p. Registered on the 18 February 2019. All items from the WHO Trial Registration Data Set can be found within the protocol. PROTOCOL VERSION: 1.0.

Impairments in episodic future thinking for positive events and anticipatory pleasure in major depression.

BACKGROUND: Characteristic of the cardinal symptom of anhedonia, people with clinical depression report lower levels of anticipatory pleasure. However, the psychological mechanisms underlying these deficits are poorly understood. This is the first study to assess whether, and to what extent, phenomenological characteristics of episodic future thinking for positive future events are associated with anticipatory pleasure among depressed individuals. METHODS: Individuals with a Major Depressive Episode (MDE; N = 117) and without (N = 47) completed ratings scales for depressive symptoms and trait anticipatory and consummatory pleasure. They then provided descriptions of personally-relevant positive future events and rated them for phenomenological characteristics and state anticipatory pleasure. RESULTS: Between-groups analysis showed that those with MDE reported lower trait anticipatory and consummatory pleasure. They also simulated future events with less specificity, less detail/vividness, less use of mental imagery, less use of first-person perspective, less plausibility/perceived likelihood of occurring, and reported less associated state anticipatory pleasure. In regression analyses in the depressed group, lower scores for detail/vividness, mental imagery, and personal significance all uniquely predicted lower state anticipatory pleasure. LIMITATIONS: Cognitive functioning was not assessed, which may help clarify deficits that underpin these findings. History of previous depressive episodes in the comparison group were not assessed, which may mean the observed between-group effects are underestimated. CONCLUSIONS: This study provides further evidence of deficits in episodic future thinking and anticipatory pleasure in depressed individuals. It also establishes links between particular characteristics of episodic future thinking and state anticipatory pleasure, and indicates cognitive targets that may be amenable to intervention in order to reduce anhedonia.

Correction: Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.

Owing to the insufficient specificity of the anti-myeloproliferative leukemia protein (MPL) antibody in the original version of this Article, Figure 6 and parts of Figures 2a, 4e, and 5a do not represent the correct information. The corrected version of Figure 6 is in this correction and those of Figures 2a, 4e, and 5a are shown in the supplemental information.

A test of the functional avoidance hypothesis in the development of overgeneral autobiographical memory.

Overgeneral memory (OGM) refers to the failure to recall memories of specific personally experienced events, which occurs in various psychiatric disorders. One pathway through which OGM is theorized to develop is the avoidance of thinking of negative experiences, whereby cumulative avoidance may maladaptively generalize to autobiographical memory (AM) more broadly. We tested this, predicting that negative experiences would interact with avoidance to predict AM specificity. In Study 1 (N = 281), negative life events (over six months) and daily hassles (over one month) were not related to AM specificity, nor was avoidance, and no interaction was found. In Study 2 (N = 318), we revised our measurements and used an increased timeframe of 12 months for both negative life events and daily hassles. The results showed no interaction effect for negative life events, but they did show an interaction for daily hassles, whereby increased hassles and higher avoidance of thinking about them were associated with reduced AM specificity, independent of general cognitive avoidance and depressive symptoms. No evidence was found that cognitive avoidance or AM specificity moderated the effect of negative experiences on depressive symptoms. Our findings suggest that life events over 6-12 months are not associated with AM specificity, but chronic daily hassles over 12 months predict reduced AM specificity when individuals avoid thinking about them. The findings provide evidence for the functional-avoidance hypothesis of OGM development and future directions for longitudinal studies.

Psychopathology and episodic future thinking: A systematic review and meta-analysis of specificity and episodic detail.

Episodic future thinking (EFT) refers to the mental simulation of future events that might be personally-experienced; a crucial mental process in adaptation. Psychiatric disorders are associated with deficits in recalling episodic memory, however, no study has reviewed the empirical literature to assess for similar deficits in EFT. A systematic review comparing psychiatric groups with control groups on the specificity and episodic detail of EFT returned 19 eligible studies. An overall effect of g = -0.84 (95%CI = -1.06, - 0.62, p < .001) indicated individuals with a psychiatric diagnosis have significantly less specific and detailed EFT. Publication bias was not detected, but heterogeneity was. No methodological characteristics were significant moderators. Subgroup analyses showed significant effects for depression (g = -0.79, p < .001, k = 7), bipolar disorder (g = -1.00, p < .001, k = 2), and schizophrenia (g = -1.06, p < .001, k = 6), but not posttraumatic stress disorder (g = -1.04, p = .260, k = 2) or complicated grief (g = -0.41, p = .08, k = 2). Deficits in EFT are apparent in some psychiatric disorders. However, many clinical groups are understudied, and the causal mechanisms and remediation of these deficits require further research attention.

Clinical characteristics and outcome of human herpesvirus-6 encephalitis after allogeneic hematopoietic stem cell transplantation.

In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11.09, P<0.001; relative risk in transplantation from HLA-mismatched unrelated donor, 9.48, P<0.001; vs transplantation from HLA-matched related donor) and GvHD prophylaxis by calcineurin inhibitor alone. At 100 days after transplantation, the overall survival rate was 58.3% and 80.5% among patients with and without HHV-6 encephalitis, respectively (P<0.001). Neuropsychological sequelae remained in 57% of 121 evaluated patients. With both foscarnet and ganciclovir, full-dose therapy (foscarnet ⩾180 mg/kg, ganciclovir ⩾10 mg/kg) was associated with better response rate (foscarnet, 93% vs 74%, P=0.044; ganciclovir, 84% vs 58%, P=0.047). HHV-6 encephalitis is not rare not only in cord blood transplant recipients but also in recipients of HLA-mismatched unrelated donors. In this study, development of HHV-6 encephalitis was associated with a poor survival rate, and neurological sequelae remained in many patients.

Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.

Myelofibrosis (MF) may be caused by various pathogenic mechanisms such as elevation in circulating cytokine levels, cellular interactions and genetic mutations. However, the underlying mechanism of MF still remains unknown. Recent studies have revealed that fibrocytes, the spindle-shaped fibroblast-like hematopoietic cells, and the thrombopoietin (TPO)/myeloproliferative leukemia protein (MPL; TPO receptor) signaling pathway play a certain role in the development of MF. In the present study, we aimed to investigate the relationship between fibrocytes and MPL activation. We showed that TPO or a TPO receptor agonist directly induces fibrocyte differentiation using murine fibrocyte cell lines and a murine MF model. Conversely, elimination of macrophages expressing MPL by clodronate liposomes reversed the MF phenotype of the murine model, suggesting that fibrocyte differentiation induced by MPL activation contributes to the progression of MF. Furthermore, we revealed that SLAMF7high MPLhigh monocytes in human peripheral blood mononuclear cells were possible fibrocyte precursors and that these cells increased in number in MF patients not treated with ruxolitinib. Our findings confirmed a link between fibrocytes and the TPO/MPL signaling pathway, which could result in a greater understanding of the pathogenesis of MF and lead to the development of novel therapeutic interventions.

Prognostic heterogeneity of the seventh edition of UICC Stage III gallbladder carcinoma: Which patients benefit from surgical resection?

BACKGROUND: This study sought to evaluate the prognostic heterogeneity of Stage III (Union for International Cancer Control, seventh edition) gallbladder carcinoma. METHODS: Of 175 patients enrolled with gallbladder carcinoma who underwent radical resection, 22 were classified with Stage IIIA disease (T3N0M0) and 46 with Stage IIIB disease (T2N1M0 [n = 23] and T3N1M0 [n = 23]). The median number of retrieved lymph nodes per patient was 18. RESULTS: This staging system failed to stratify outcomes between Stages IIIA and IIIB; survival after resection was better for patients with Stage IIIB disease than for patients with Stage IIIA disease, with 5-year survival of 54.9% and 41.0%, respectively (p = 0.366). Multivariate analysis for patients with Stage III disease revealed independently better survival for patients with T2N1M0 than for patients with T3N0M0 (p = 0.016) or T3N1M0 (p = 0.001), with 5-year survival of 77.0%, 41.0%, and 31.0%, respectively. When N1 status was subdivided according to the number of positive nodes, 5-year survival in patients with T2M0 with 1-2 positive nodes, T2M0 with ≥3 positive nodes, T3M0 with 1-2 positive nodes, and T3M0 with ≥3 positive nodes was 83.3%, 50.0%, 45.8%, and 0%, respectively (p < 0.001). CONCLUSIONS: The prognosis of T2N1M0 disease was better than that of T3N0/1M0 disease, suggesting that not all node-positive patients will have uniformly poor outcomes after resection of gallbladder carcinoma. T2M0 with 1-2 positive nodes leads to a favorable outcome after resection, whereas T3M0 with ≥3 positive nodes indicates a dismal prognosis.

Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas.

BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.

Adult living-donor liver transplantation for a recipient with a high preoperative 1,3-beta-D-glucan level and positive test result for Aspergillus antigen.

The patient was a 45-year-old man with underlying alcoholic liver cirrhosis. Two years prior, he was repeatedly hospitalized for liver failure symptoms and requested a living-donor liver transplantation (LDLT) because of end-stage cirrhosis. A pretransplantation blood test revealed a high 1,3-beta-d-glucan (BDG) value of 102.0 pg/mL (reference value <20.0 pg/mL) and a high blood Aspergillus antigen (AsAg) value of 1.6 cutoff index (COI; reference value <0.5 COI). Contrast-enhanced thoracoabdominal-pelvic computed tomography (CT) and cranial magnetic resonance imaging revealed no fungal infection. However, latent fungal infection could not be ruled out, hence preoperative antifungal agent treatment was administered. BDG and AsAg levels showed a decreasing trend after treatment initiation. However, normalization did not occur; the BDG and AsAg levels were 25.8 pg/mL and 1.0 COI, respectively. Although the possibility of latent fungal infection was judged low, we prophylactically administered antifungal agents after LDLT. The BDG level consistently increased at 35-39 pg/mL until postoperative day 5 but subsequently normalized. The AsAg level was higher than the limit of detection at 5.0 COI on postoperative day 3 but normalized to 0.2 COI on postoperative day 5 and did not subsequently increase. The postoperative course was uneventful despite bacterial pneumonia and the patient was discharged on postoperative day 35. A histopathologic examination (Grocott methenamine silver staining) and a fungal polymerase chain reaction assay were performed for the resected liver, but the results of both were negative. At 9 postoperative months, the patient was making ambulatory follow-up visits. Currently, the BDG and AsAg values remain normal and clinical progress is favorable. We found no reports of LDLT for a recipient with a high preoperative BDG level and positive test result for AsAg. Thus, we report on such a case with a discussion of the literature on the causes of high preoperative BDG and AsAg values.

Pre-transplant diabetes mellitus is a risk factor for non-relapse mortality, especially infection-related mortality, after allogeneic hematopoietic SCT.

Diabetes mellitus (DM) is a factor in the hematopoietic cell transplantation-comorbidity index. However, the impact of pre-transplant DM on morbidity and cause-specific non-relapse mortality (NRM) remains unclear. We performed a retrospective study with registry data that included a total of 7626 patients who underwent their first allogeneic hematopoietic SCT (HSCT) between 2007 and 2010. The median age was 44 years (range 0-88). Compared with patients without pre-transplant DM (non-DM group, n=7248), patients with pre-transplant DM (DM group, n=378) were older and were more likely to have high-risk disease, a reduced-intensity conditioning regimen and GVHD prophylaxis using tacrolimus. Multivariate analyses showed that pre-transplant DM was associated with increased risks of NRM (hazard ratio (HR)1.46, 95% confidence interval (CI) 1.21-1.76, P<0.01) and infection-related NRM (HR 2.08, 95% CI 1.58-2.73, P<0.01). The presence of pre-transplant DM was associated with an increased risk of overall mortality in a multivariate analysis (HR 1.55, 95% CI 1.35-1.78, P<0.01). In conclusion, pre-transplant DM was a risk factor for NRM, particularly infection-related mortality, after allogeneic HSCT. To improve the clinical outcome in patients with DM, the benefits of strict infection control and appropriate glycemic control should be explored in future trials.

Impact of pretransplant body mass index on the clinical outcome after allogeneic hematopoietic SCT.

To elucidate the impact of pretransplant body mass index (BMI) on the clinical outcome, we performed a retrospective study with registry data including a total of 12 050 patients (age ⩾18 years) who received allogeneic hematopoietic SCT (HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5 kg/m(2), Underweight, n=1791; 18.5⩽BMI<25, Normal, n=8444; 25⩽BMI<30, Overweight, n=1591; BMI⩾30, Obese, n=224. The median age was 45 years (range, 18-77). A multivariate analysis showed that the risk of relapse was significantly higher in the underweight group and lower in the overweight and obese groups compared with the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The risk of GVHD was significantly higher in the overweight group compared with the normal group. The risk of non-relapse mortality (NRM) was significantly higher in the overweight and obese group compared with the normal group (HR 1.19 and HR 1.43, respectively). The probability of OS was lower in the underweight group compared with the normal group (HR 1.10, P=0.018). In conclusion, pretransplant BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a risk factor for poor OS because of an increased risk of relapse. Obesity was a risk factor for NRM.

Laparoscope-assisted Hassab's operation for esophagogastric varices after living donor liver transplantation: a case report.

This is the first successful report of a laparoscope-assisted Hassab's operation for esophagogastric varices after living donor liver transplantation (LDLT). A 35-year-old man underwent LDLT using a right lobe graft as an aid for primary sclerosing cholangitis (PSC) in 2005. Follow-up endoscopic and computed tomography (CT) examinations showed esophagogastric varices with splenomegaly in 2009 that increased (esophageal varices [EV]: locus superior [Ls], moderator enlarged, beady varices [F2], medium in number and intermediate between localized and circumferential red color signs [RC2]; gastric varices [GV]: extension from the cardiac orifice to the fornix [Lg-cf], moderator enlarged, beady varices [F2], absent red color signs [RC0]). A portal venous flow to the esophagogastric varices through a large left gastric vein was also confirmed. Preoperative Child-Pugh was grade B and score was 9. Because these esophagogastric varices had a high risk of variceal bleeding, we proceeded with a laparoscope-assisted Hassab's operation. Operative time was 464 minutes. Blood loss was 1660 mL. A graft liver biopsy was also performed and recurrence of PSC was confirmed histologically. It was suggested that portal hypertension and esophagogastric varices were caused by recurrence of PSC. Postoperative complications were massive ascites and enteritis. Both of them were treated successfully. This patient was discharged on postoperative day 43. Follow-up endoscopic study showed improvement in the esophagogastric varices (esophageal varices [EV]: locus superior [Ls], no varicose appearance [F0], absent red color signs [RC0], gastric varices [GV]: adjacent to the cardiac orifice [Lg-c], no varicose appearance [F0], absent red color signs [RC0]) at 6 months after the operation. We also confirmed the improvement of esophagogastric varices by serial examinations of CT.

Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects.

This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the ß-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 µmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.