Improving the self-report of HIV antiretroviral medication adherence: Is the glass half full or half empty?

Self-reports are the most widely used method for measuring antiretroviral adherence. The association between self-reports and viral loads has been repeatedly demonstrated, but this association does not address how well self-reports measure actual medication-taking behaviors. Understanding adherence self-reports requires studying the science of memory and the reporting of behaviors. In the first section of this review, we discuss research in cognitive psychology that pertains to adherence self-reports, focusing primarily on studies that examine cognitive processes respondents use to answer survey questions. In the second section, we review recent articles examining the relationship between self-reports and objective measures of adherence, highlighting the strength of associations and key methodologic issues. We conclude with key questions for future research and methodologic recommendations.     

Type 1 diabetes immunotherapy: is the glass half empty or half full?

Reevaluation of clinical data from the recent failed immunotherapy trials suggests that researchers should continue the quest to cure type 1 diabetes with immune therapies.     

Will the glass be half full or half empty? Brain potentials and emotional expectations

Brainwave responses to words in context depend on semantic and world-knowledge expectations. Using the N400 component of event-related potentials as an index of word expectation, we explored brain responses to negatively and positively biased sentence frames randomly presented with their emotionally matched highly expected outcome or with violations that included switches to unexpected emotionally opposite outcomes or nonsense. Nonsense elicited large N400 responses regardless of the bias of the preceding sentence frame. Unexpected emotionally opposite outcomes elicited smaller than nonsense N400 responses and subsequent post-N400 frontal positivities, both unaffected by sentence frame bias. Over a midline-posterior scalp region, expected positive outcomes elicited larger N400 responses than negative ones, despite a high and matched word probability. Our study reveals that brains respond to unexpected emotional outcomes regardless of the direction of the emotional switch and hints at the possibility that the strength of positive and negative expectations may be adjusted before experiencing unexpected events.     

Is the glass half empty or half full? A prospective study of optimism and coronary heart disease in the normative aging study.

OBJECTIVE: A sense of optimism, which derives from the ways individuals explain causes of daily events, has been shown to protect health, whereas pessimism has been linked to poor physical health. We examined prospectively the relationship of an optimistic or pessimistic explanatory style with coronary heart disease incidence in the Veterans Affairs Normative Aging Study, an ongoing cohort of older men. METHODS AND RESULTS: In 1986, 1306 men completed the revised Minnesota Multiphasic Personality Inventory, from which we derived the bipolar revised Optimism-Pessimism Scale. During an average of 10 years of follow-up, 162 cases of incident coronary heart disease occurred: 71 cases of incident nonfatal myocardial infarction, 31 cases of fatal coronary heart disease, and 60 cases of angina pectoris. Compared with men with high levels of pessimism, those reporting high levels of optimism had multivariate-adjusted relative risks of 0.44 (95% confidence interval = 0.26-0.74) for combined nonfatal myocardial infarction and coronary heart disease death and 0.45 (95% confidence interval = 0.29-0.68) for combined angina pectoris, nonfatal myocardial infarction, and coronary heart disease death. A dose-response relation was found between levels of optimism and each outcome (p value for trend,.002 and.0004, respectively). CONCLUSIONS: These results suggest that an optimistic explanatory style may protect against risk of coronary heart disease in older men.     

Molecular mimicry in the MHC: Hidden clues to autoimmunity?

The term ‘molecular mimicry’ has been used to describe a spectrum of antigenic crossreactivities thought to underlie autoimmune disease. For T cell crossreactivities to occur appropriate T cell clone must be available. Here Harold Baum, Huw Davies and Mark Peakman speculate that an important source of self-peptides that govern thymic selection of such clones are MHC molecular themselves.     

Best site for embryo transfer: the upper or lower half of endometrial cavity?

BACKGROUND: The objective of the present study was to determine the importance of the site of embryo transfer (upper or lower half endometrial cavity) on implantation and clinical pregnancy rates. METHODS: A total of 400 transfers guided by ultrasound were randomly assigned to two groups according to the distance between the uterine fundus and the catheter tip at the time of embryo placement. Group I (n = 200) consisted of transfers corresponding to a distance of < 50% of the endometrial cavity length (ECL), i.e. transfer in upper half of the cavity; and group II (n = 200) consisted of transfers corresponding to a distance of > or = 50%, of the ECL, i.e. transfer in lower half of cavity. The Student's t-test, Mann-Whitney test and Fisher's exact test were used where appropriate. RESULTS: The general characteristics of the study population and the main transfer cycle characteristics had an equal distribution (P > 0.05) between groups I and II. No significant difference in implantation or pregnancy rates was observed between groups I and II. CONCLUSION: The implantation or pregnancy rates were similar whether the embryos were deposited in the upper or lower half of the endometrial cavity.     

β2-microglobulin is required for the full expression of xenobiotic-induced systemic autoimmunity

Mercury exposure in both humans and mice is associated with features of systemic autoimmunity. Murine HgCl₂-induced autoimmunity (mHgIA) requires MHC Class II, CD4⁺ T-cells, co-stimulatory molecules, and interferon-γ (IFN-γ), similar to spontaneous models of systemic lupus erythematosus (SLE). β₂-microglobulin (B2m) is required for functional MHC Class I molecules and the neonatal F_c receptor (F_cRn). Deficiency of B2m in lupus-prone strains is consistently associated with reduced IgG levels, but with variable effects on other manifestations. Herein, we examined the role of B2m in mHgIA and show that in the absence of B2m, mercury-exposed mice failed to exhibit hypergammaglobulinemia, had reduced anti-nucleolar autoantibodies (ANoA), and had a lower incidence of immune complex deposits in splenic blood vessels, whereas IgG anti-chromatin autoantibodies and renal immune deposits were largely unaffected. Subclass analysis of the IgG anti-chromatin, however, revealed a significant reduction in the IgG₁ subtype. Examination of IFNγ, IL-4, and IL-2 in exposed skin, draining lymph nodes, and spleen following mercury exposure showed reduced IL-4 in the spleen and skin in B2m-deficient mice, consistent with the lower IgG₁ anti-chromatin levels, and reduced IFNγ expression in the skin. These findings demonstrate how a single genetic alteration can partially but significantly modify the clinical manifestations of systemic autoimmunity induced by exposure to xenobiotics.     

β2-microglobulin is required for the full expression of xenobiotic-induced systemic autoimmunity

Mercury exposure in both humans and mice is associated with features of systemic autoimmunity. Murine HgCl?-induced autoimmunity (mHgIA) requires MHC Class II, CD4? T-cells, co-stimulatory molecules, and interferon-γ (IFN-γ), similar to spontaneous models of systemic lupus erythematosus (SLE). β?-microglobulin (B2m) is required for functional MHC Class I molecules and the neonatal F(c) receptor (F(c)Rn). Deficiency of B2m in lupus-prone strains is consistently associated with reduced IgG levels, but with variable effects on other manifestations. Herein, we examined the role of B2m in mHgIA and show that in the absence of B2m, mercury-exposed mice failed to exhibit hypergammaglobulinemia, had reduced anti-nucleolar autoantibodies (ANoA), and had a lower incidence of immune complex deposits in splenic blood vessels, whereas IgG anti-chromatin autoantibodies and renal immune deposits were largely unaffected. Subclass analysis of the IgG anti-chromatin, however, revealed a significant reduction in the IgG? subtype. Examination of IFNγ, IL-4, and IL-2 in exposed skin, draining lymph nodes, and spleen following mercury exposure showed reduced IL-4 in the spleen and skin in B2m-deficient mice, consistent with the lower IgG? anti-chromatin levels, and reduced IFNγ expression in the skin. These findings demonstrate how a single genetic alteration can partially but significantly modify the clinical manifestations of systemic autoimmunity induced by exposure to xenobiotics.     

Aging of the immune system: a risk factor for autoimmunity?

Aging of the immune system, or immunosenescence, is characterized by changes in T cell subsets, cellular and molecular level alterations and thymic atrophy, resulting in a decline of T and B cell function. These alterations have been shown to be accompanied by a loss of ability to recognize "self" and "foreign" antigens. Therefore the development of autoimmune responses like production of autoantibodies has been hypothesized to be secondary to thymus involution with a decline of na?ve T cells and accumulation of clonal T cells with activation due to "neoantigens" during the aging process. Altered apoptosis and altered T cell homeostasis have been emphasized to promote a chronic inflammatory state and lead to the concept of a immune-risk phenotype. However, it has to be proven which kinds of mechanisms turn the immune system to manifest autoimmune disease and how speculated defects in T cell differentiation and interaction leading to premature aging of the immune system may contribute to the development of autoimmune diseases.     

Coexistence of thyroid autoimmunity with other autoimmune diseases: friend or foe? Additional aspects on the mosaic of autoimmunity

Autoimmunity encompasses a wide spectrum of diseases from organ-specific diseases like Hashimoto thyroiditis, to systemic diseases such as systemic lupus erythematosus. These diseases are characterized by inflammation and the production of a wide range of autoantibodies directed against multiple autoantigens. Although their etiology is still poorly understood, genetic, immunological, hormonal, and environmental factors are major predisposing and triggering factors. These multiple factors, like pieces in a mosaic, may interplay in different forms, leading to the expression of various autoimmune manifestations and diseases. This phenomenon, which has been referred by us as the "mosaic of autoimmunity", illuminates the diversity of autoimmune manifestations among susceptible individuals. From this theoretical framework we conducted a wide search of the literature, on the prevalence of thyroid autoimmunity, the commonest of the autoimmune conditions, among other autoimmune diseases, and discuss the possible clinical significance of this association.     

Is the Era of Viral Culture Over in the Clinical Microbiology Laboratory?

Conventional tube culture systems have long been the mainstay in clinical virology for the growth and identification of viruses from clinical specimens. Innovations such as centrifugation-enhanced shell vial and multiwell plate cultures and the use of genetically engineered and mixed cell lines, coupled with faster detection of viral replication, have allowed for reasonable turnaround times for even some of the most slowly growing clinically important human viruses. However, molecular methods, in particular, the PCR, have usurped the role of viral culture in many laboratories, limiting the use of this traditional method of virus detection or replacing it altogether. Advances and improvements in molecular technology over time have also resulted in newer generations of more rapid and accurate molecular assays for the detection, quantification, and genetic characterization of viruses. For this point-counterpoint, we have asked two individuals, Richard L. Hodinka of the Children''s Hospital of Philadelphia, a clinical virologist whose laboratory has completely eliminated viral culture in favor of molecular methods, and Laurent Kaiser, head of the Virology Laboratory at the University of Geneva Hospital, who continues to be a strong advocate of viral culture, to discuss the relevance of viral culture in the molecular age.

• J Clin Microbiol. 2013 Jan; 51(1): 2–8.
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• Sub-article 1

2013 Jan; 51(1): 2–8. doi: 10.1128/JCM.02593-12 Copyright and License information DisclaimerCopyright notice     

Viral apoptotic mimicry: an immune evasion strategy developed by the hepatitis B virus?

The co-existence of viruses and organisms for millions of years has influenced the evolution of both. Various viral strategies to enter a host and take over the control of cells to produce virus progeny have developed. Several antiviral (immune) responses have also been developed. The apoptotic death program is a conserved feature of eukaryotic cells. In multicellular organisms the binding and engulfment of apoptotic material is considered to be the end stage of the apoptotic process. Because of its importance, it seems probable that viruses have targeted this ancient removal system to suppress immune responses and to establish or maintain infection. The possibility that the hepatitis B virus has evolved such a mechanism, termed "viral apoptotic-like mimicry", is presented here.