Association of Killer Cell Immunoglobulin-Like Receptor Genes with Hodgkin's Lymphoma in a Familial Study

BACKGROUND: Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study. METHODOLOGY: We included 90 families with 90 HL index cases (age 16–35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families. PRINCIPAL FINDINGS: Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23–0.85] and 0.42[0.21–0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18–71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells. CONCLUSIONS: This work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL

Application of elaborated intrusion theory to the measurement and enhancement of motivation in type 2 diabetes

This thesis examined the relationship between mental imagery and motivation for self-care in chronic disease management. A scale measuring frequency of health cognitions found greater motivation in those frequently imagining change. However, an intervention designed to increase frequency and intensity of these health cognitions found no change in behaviour. This research demonstrated that imagery-based training may not be effective in sustaining motivation in chronic health, but leaves open the possibility that it could assist in initial stages of disease management

S-adenosylmethionine (SAMe) and Magnesium Orotate as adjunctives to SSRIs in sub-optimal treatment response of depression in adults: A pilot study

Major depression is a prevalent mental health disorder and a proportion of patients do not respond adequately to standard treatment. The use of nutraceutical adjunctives with antidepressant medication such as high dose S-adenosylmethionine (SAMe) has proven beneficial in terms of initial symptom response but the effect on symptom maintenance and relapse is unknown. In this pilot study [n = 36], participants [26 evaluable subjects] with established sub-optimal response to treatment for major depressive disorder and who were prescribed Selective Serotonin Reuptake Inhibitor (SSRI) medication were randomly allocated to either 1600 mg or 800 mg daily of SAMe for 15 weeks duration to evaluate the efficacy on both symptom response and maintenance. A variety of validated psychiatric measures of symptoms and mood including clinician assessment and self-report measures were used to assess outcome measures. Both SAMe doses achieved similar results with a significant proportion of participants (35%) achieving significant symptom improvement at the end of 15 weeks supplementation as assessed by the Beck Depression Inventory (BDI), Outcome Questionnaire 45 (OQ45), and improved Quality of Life (QOL) scores. After a 2 week washout period, SAMe non-responders were then supplemented with 1600 mg of Magnesium Orotate for 8 weeks duration which resulted in significant clinical improvement as measured by BDI, OQ45 and QOL scores [n = 8]. We progress the SAMe-methylation and Orotate–uridine hypothesis and consider that the response to these novel compounds implicates the microbiome as an important agent for the adjunctive treatment of sub-optimal response to pharmaceutical medications

The new ‘5-HT’ hypothesis of depression : cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute

<b>Purpose</b>\ud \ud - There is a need for improved measurement of motivation for diabetes self-care. The Elaborated Intrusion Theory of Desire offers a coherent framework for understanding and identifying the cognitive-affective events that constitute the subjective experience of motivation, and may therefore inform the development of such an instrument. Recent research has shown the resultant <i>Motivation Thought Frequency scale (MTF)</i> to have a stable factor structure (Intensity, Incentives Imagery, Self-Efficacy Imagery, Availability) when applied to physical activity, excessive snacking, or alcohol use in the general population. The current study aimed to confirm the 4-factor structure of the MTF for glucose testing, physical activity and healthy eating in people with type 2 diabetes. Associations with self-reports of concurrent diabetic self-care behaviours were also examined.\ud \ud <b>Method</b>\ud \ud - Confirmatory factor analyses tested the internal structure, and multiple regressions assessed the scale’s relationship with concurrent self-care behaviours. The MTF was completed by 340 adults with type 2 diabetes, and 237 from that sample also reported self-care behaviours. Separate MTFs assessed motivation for glucose testing, physical activity and healthy eating. Self-care was assessed using questions from the Summary of Diabetes Self-Care Activities.\ud \ud <b>Results</b>\ud \ud - The MTF for each goal achieved acceptable fit on all indices after selected errors within factors were allowed to intercorrelate. Intensity and Self-Efficacy Imagery provided the strongest and most consistent correlations with relevant self-care behaviours. \ud \ud <b>Conclusions</b>\ud \ud - Results provide preliminary support for the MTF in a diabetes sample. Testing of its sensitivity to change and its predictive utility over time is needed

Functional Imagery Training versus Motivational Interviewing for Weight Loss: A randomised controlled trial of brief individual interventions for overweight and obesity

Objective: Functional Imagery Training (FIT) is a new brief motivational intervention based on the Elaborated Intrusion theory of desire. FIT trains the habitual use of personalised, affective, goal-directed mental imagery to plan behaviours, anticipate obstacles, and mentally try out solutions from previous successes. It is delivered in the client-centred style of Motivational Interviewing (MI). We tested the impact of FIT on weight loss, compared with time- and contact-matched MI. Design: We recruited 141 adults with BMI (kg/m²) ≥25, via a community newspaper, to a single-centre randomised controlled trial. Participants were allocated to one of two active interventions: FIT or MI. Primary data collection and analyses were conducted by researchers blind to interventions. All participants received two sessions of their allocated intervention; the first face-to-face (1 h), the second by phone (maximum 45 min). Booster calls of up to 15 min were provided every 2 weeks for 3 months, then once-monthly until 6 months. Maximum contact time was 4 h of individual consultation. Participants were assessed at Baseline, at the end of the intervention phase (6 months), and again 12 months post-baseline. Main outcome measures: Weight (kg) and waist circumference (WC, cm) reductions at 6 and 12 months. Results: FIT participants (N = 59) lost 4.11 kg and 7.02 cm of WC, compared to.74 kg and 2.72 cm in the MI group (N = 55) at 6 months (weight mean difference (WMD) = 3.37 kg, p <.001, 95% CI [−5.2, −2.1], waist-circumference mean difference (WCMD) = 4.3 cm, p <.001, 95% CI [−6.3,−2.6]). Between-group differences were maintained and increased at month 12: FIT participants lost 6.44 kg (W) and 9.1 cm (WC) compared to the MI who lost.67 kg and 2.46 cm (WMD = 5.77 kg, p <.001, 95% CI [−7.5, −4.4], WCMD = 6.64 cm, p <.001, 95% CI [−7.5, −4.4]). Conclusion: FIT is a theoretically informed motivational intervention which offers substantial benefits for weight loss and maintenance of weight reduction, compared with MI alone, despite including no lifestyle education or advice.</p

Functions of natural killer cells.

International audienceNatural killer (NK) cells are effector lymphocytes of the innate immune system that control several types of tumors and microbial infections by limiting their spread and subsequent tissue damage. Recent research highlights the fact that NK cells are also regulatory cells engaged in reciprocal interactions with dendritic cells, macrophages, T cells and endothelial cells. NK cells can thus limit or exacerbate immune responses. Although NK cells might appear to be redundant in several conditions of immune challenge in humans, NK cell manipulation seems to hold promise in efforts to improve hematopoietic and solid organ transplantation, promote antitumor immunotherapy and control inflammatory and autoimmune disorders

Targeting natural killer cells and natural killer T cells in cancer.

International audienceNatural killer (NK) cells and natural killer T (NKT) cells are subsets of lymphocytes that share some phenotypical and functional similarities. Both cell types can rapidly respond to the presence of tumour cells and participate in antitumour immune responses. This has prompted interest in the development of innovative cancer therapies that are based on the manipulation of NK and NKT cells. Recent studies have highlighted how the immune reactivity of NK and NKT cells is shaped by the environment in which they develop. The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans