Childhood trauma, posttraumatic stress disorder symptoms, early maladaptive schemas, and schema modes : a comparison of individuals with obesity and normal weight controls

Background: Previous research on the psychological mechanisms of obesity has primarily focused on acute psychopathology. However, there is limited literature on the role of more complex and entrenched psychological processes in weight management. The current study aimed to expand previous research by examining more enduring psychological constructs, including early maladaptive schemas (EMS), schemas modes, and trauma. Methods: Participants (N=125) comprised adults with normal weight (n=40) and obesity (n=85) from community and clinical settings in Australia. Eligible participants completed a series of self-report questionnaires via Research Electronic Data Capture (REDCap). Two, separate, one-way multivariate analysis of variance (MANOVA) were conducted to examine group differences on the outcome variables. Results: Findings indicated a significant effect of group on EMS and schema modes, V=.51, F(32, 92)=2.97, p<.001, partial η2=.51. Follow-up univariate tests revealed that individuals with obesity endorsed significantly more maladaptive schemas and schema modes and significantly less healthy schema modes than individuals with normal weight. In addition, results demonstrated a significant effect of group on childhood trauma and posttraumatic stress disorder (PTSD) symptoms, V=.19, F(6, 118)=4.70, p<.001, partial η2=.19. Subsequent univariate tests and chi-square analyses indicated that individuals with obesity reported significantly more childhood trauma as well as significantly more PTSD symptoms within the last month than normal weight individuals. Conclusion: This was the first study to compare EMS and schema modes in treatment-seeking individuals with obesity and normal weight controls using the short form version 3 of the Young Schema Questionnaire and revised, 118-item, Schema Mode Inventory. Overall, findings revealed that individuals with obesity experience more complex and enduring psychological difficulties than normal weight individuals. Increased assessment and targeted treatment of these underlying mental health concerns may contribute to a more holistic conceptualisation of obesity and could improve the long-term success of weight management

Efficacy of telephone health coaching integration with standard multidisciplinary care for adults with obesity attending a weight management service : a pilot study

Australia has one of the highest prevalences of obesity in the developed world with recognised gaps in patient access to obesity services. This non-randomised before and after study investigated the health benefits and patient acceptability of integrating the Get Healthy Service, a state-funded telephone-delivered coaching service in Australia, as an adjunct to multidisciplinary care for adults attending a public obesity service. Forty-one participants received multidisciplinary care alone while 39 participants were subsequently allocated to receive adjunctive treatment with the Get Healthy Service. Weight, body mass index, glycosylated haemoglobin, measurement of hepatic steatosis and liver enzymes were collected at baseline and 6 months. Participant evaluation was obtained post intervention. Statistically significant reductions from baseline were achieved for both control and intervention with respect to weight (−6.7 ± 2.2 kg, p = 0.01; −12.6 ± 3.2, p = 0.002), body mass index (−2.3 ± 0.8, p = 0.01; −4.8 ± 1.2 kg/m2 , p = 0.002) and glycosylated haemoglobin (−0.2 ± 0.2%, p = 0.2 (NS); −0.7 ± 0.2%, p = 0.02), respectively. There were no significant differences in steatosis or liver enzymes or in outcomes between control and intervention cohorts. A high level of patient acceptability was reported. Integrating telephone-delivered coaching provided non-inferior care and high levels of patient satisfaction. Telephone coaching aligned with the principles of an obesity service should be trialled to improve patient access to obesity interventions

The role of gut-derived microbial antigens on liver fibrosis initiation and progression

Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis

The psychometric properties of the grazing questionnaire in an obesity sample with and without binge eating disorder

Background: Despite being the first validated measure of grazing, the Grazing Questionnaire (GQ) has not been investigated among individuals with obesity. Therefore, the current study aimed to examine the psychometric properties of the GQ in an obesity sample. Methods: Participants (N=259) were recruited from community and clinical settings in Australia. The sample comprised adults with normal weight (n=77) and obesity (n=182). A portion of individuals with obesity (n=102) had binge eating disorder (BED). Data from the obesity group was examined to establish the factor structure, validity, and reliability of the GQ. A one-way ANOVA with planned contrasts was conducted to compare scores on the GQ across groups. Results: Confirmatory factor analysis revealed that the 2-factor model of the GQ was the best model ft for individuals with obesity. The GQ demonstrated high internal consistency, test–retest reliability over 3 months, and convergent and divergent validity. As hypothesised, the obesity group had significantly higher scores on the GQ than the normal weight group, while the obesity with BED group had significantly higher scores than the obesity without BED group. Conclusion: This was the first study to investigate the psychometric properties of the GQ in an obesity sample. Overall, findings indicated that the GQ is a psychometrically sound measure of grazing among individuals with obesity. These findings provide further support for two distinct subtypes of grazing and highlight the importance of increased assessment and management of grazing behaviours for individuals with obesity and eating disorders. Plain English summary: Maintaining a healthy weight is one of the greatest challenges for individuals with obesity. Certain eating patterns such as grazing may contribute to difficulties in weight management. Grazing is the repetitive and unplanned eating of small amounts of food that is not related to feeling hungry. Researchers and clinicians often use self-report questionnaires to measure grazing. However, the first validated questionnaire of grazing has not been investigated among individuals with obesity. Therefore, the goal of this study was to examine and validate the Grazing Questionnaire in individuals with obesity. Overall, our results showed that the Grazing Questionnaire is a valid and reliable self-report measure of grazing in individuals with obesity. Similar to previous research, we found that there are two subtypes of grazing. The first subtype involves continuous, unplanned eating. The second subtype is associated with a sense of loss of control over eating. We also found that people with obesity and binge eating disorder graze more than people with obesity that do not have binge eating disorder, while both groups graze more than individuals with normal weight. We recommend that clinicians routinely assess and treat unhelpful grazing patterns when working with individuals with obesity and eating disorders

Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional overdose causes acute liver failure characterized by centrilobular hepatic necrosis with high morbidity and mortality. Although many molecular aspects of APAP-induced cell death have been described, no conclusive mechanism has been proposed. We recently identified TNF-related apoptosis-inducing ligand (TRAIL) and c-Jun kinase (JNK)-dependent activation of the pro-apoptotic Bcl-2 homolog Bim as an important apoptosis amplification pathway in hepatocytes. In this study, we, thus, investigated the role of TRAIL, c-JNK and Bim in APAP-induced liver damage. Our results demonstrate that TRAIL strongly synergizes with APAP in inducing cell death in hepatocyte-like cells lines and primary hepatocyte. Furthermore, we found that APAP strongly induces the expression of Bim in a c-JNK-dependent manner. Consequently, TRAIL- or Bim-deficient mice were substantially protected from APAP-induced liver damage. This study identifies the TRAIL-JNK-Bim axis as a novel target in the treatment of APAP-induced liver damage and substantiates its general role in hepatocyte death

TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients

<p>Abstract</p> <p>Background</p> <p>Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (<it>DR4</it>) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed <it>DR4 </it>mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC.</p> <p>Methods</p> <p>Frequencies of <it>DR4 </it>gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population.</p> <p>Results</p> <p>Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. <it>DR4 </it>variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007). Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 10⁶ IU/ml vs. 1.81 ± 0.23 × 10⁶ IU/ml, p = 0.049).</p> <p>Conclusions</p> <p>The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.</p

CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver

This work was funded by a Wellcome Trust Investigator Award to MKM funding KS and LP, MRC Career Development Award to CD, MRC Clinical Research Training Fellowship to DP, Wellcome Trust Henry Dale Fellowship to VM

Treatment of Hepatitis C as Prevention: A Modeling Case Study in Vietnam

Background: Treatment of hepatitis C (HCV) is very effective, achieving a cure in 50–90 % of patients. Besides its own good for individuals, this most likely translates in reduced transmission, but this phenomenon has yet to be fully explored. Methods and Findings: In this mathematical modeling study done in the context of Vietnam, we estimated the public health benefit that HCV therapy for injecting drug users (IDUs) may achieve. Treatment coverage of 25, 50 and 75 % of chronically HCV-infected IDUs (4 years into infection) is predicted to reduce the chronic HCV viremia prevalence respectively by 21, 37 and 50%, 11 years after full scale up to the intended coverage. At a constant 50 % coverage level, earlier treatment, 3, 2, and 1 year into infection is predicted to reduce the chronic HCV viremia prevalence by 46, 60 and 85%. In these later 3 scenarios, for every 100 treatment courses provided, a total of respectively 50, 61 and 94 new infections could be averted. These benefits were projected in the context of current low coverage of methadone maintenance therapy and needles/ syringes exchange programs, and these services expansion showed complementary preventive benefits to HCV therapy. The program treatment commitment associated with the various scenarios is deemed reasonable. Our model projections are robust under adjustment for uncertainty in the model parameter values. Conclusions: In this case study in Vietnam, we project that treatment of HCV for injecting drug users will have a preventative herd effect in addition to curing patients in need for therapy, achieving a substantial reduction in HCV transmission an

Reduction of Natural Killer but Not Effector CD8 T Lymphoyctes in Three Consecutive Cases of Severe/Lethal H1N1/09 Influenza A Virus Infection

Background: The cause of severe disease in some patients infected with pandemic influenza A virus is unclear. Methodology/Principal Findings: We present the cellular immunology profile in the blood, and detailed clinical (and postmortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients. Conclusion/Significance: Our report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype