Four-year follow-up of imprisoned male heroin users and methadone treatment: mortality, re-incarceration and hepatitis C infection

AIMS: To examine the long-term impact of methadone maintenance treatment (MMT) on mortality, re-incarceration and hepatitis C seroconversion in imprisoned male heroin users. DESIGN, SETTING AND PARTICIPANTS: The study cohort comprised 382 imprisoned male heroin users who had participated in a randomized controlled trial of prison-based MMT in 1997/98. Subjects were followed-up between 1998 and 2002 either in the general community or in prison. MEASUREMENTS: All-cause mortality, re-incarceration, hepatitis C and HIV serostatus and MMT retention. FINDINGS: There were no deaths recorded while subjects were enrolled in MMT. Seventeen subjects died while out of MMT, representing an untreated mortality rate of 2.0 per 100 person-years (95% CI, 1.2-3.2). Re-incarceration risk was lowest during MMT episodes of 8 months or longer (adjusted hazard ratio 0.3 (95% CI, 0.2-0.5; P < 0.001), although MMT periods 2 months or less were associated with greatest risk of re-incarceration (P < 0.001). Increased risk of hepatitis C seroconversion was significantly associated with prison sentences of less than 2 months [adjusted hazard ratio 20 (95% CI, 5-76; < P = 0.001)] and MMT episodes less than 5 months [adjusted hazard ratio 4.2 (95% CI, 1.4-12.6; P = 0.01)]. Subjects were at greatest risk of MMT dropout during short prison sentences of 1 month or less (adjusted hazard ratio 10.4 (95% CI, 7.0-15.7; P < 0.001). HIV incidence was 0.3 per 100 person-years (95% CI, 0.03-0.99). CONCLUSIONS: Retention in MMT was associated with reduced mortality, re-incarceration rates and hepatitis C infection. Prison-based MMT programmes are integral to the continuity of treatment needed to ensure optimal outcomes for individual and public health.     

What the heart forgets: Cardiac timing influences memory for words and is modulated by metacognition and interoceptive sensitivity

Mental functions are influenced by states of physiological arousal. Afferent neural activity from arterial baroreceptors at systole conveys the strength and timing of individual heartbeats to the brain. We presented words under limited attentional resources time‐locked to different phases of the cardiac cycle, to test a hypothesis that natural baroreceptor stimulation influences detection and subsequent memory of words. We show memory for words presented around systole was decreased relative to words at diastole. The deleterious memory effect of systole was greater for words detected with low confidence and amplified in individuals with low interoceptive sensitivity, as indexed using a heartbeat counting task. Our observations highlight an important cardiovascular channel through which autonomic arousal impacts a cognitive function, an effect mitigated by metacognition (perceptual confidence) and interoceptive sensitivity.     

High Wall Shear Stress and Spatial Gradients in Vascular Pathology: A Review

Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.     

The Use of Imputed Sibling Genotypes in Sibship-Based Association Analysis: On Modeling Alternatives, Power and Model Misspecification

When phenotypic, but no genotypic data are available for relatives of participants in genetic association studies, previous research has shown that family-based imputed genotypes can boost the statistical power when included in such studies. Here, using simulations, we compared the performance of two statistical approaches suitable to model imputed genotype data: the mixture approach, which involves the full distribution of the imputed genotypes and the dosage approach, where the mean of the conditional distribution features as the imputed genotype. Simulations were run by varying sibship size, size of the phenotypic correlations among siblings, imputation accuracy and minor allele frequency of the causal SNP. Furthermore, as imputing sibling data and extending the model to include sibships of size two or greater requires modeling the familial covariance matrix, we inquired whether model misspecification affects power. Finally, the results obtained via simulations were empirically verified in two datasets with continuous phenotype data (height) and with a dichotomous phenotype (smoking initiation). Across the settings considered, the mixture and the dosage approach are equally powerful and both produce unbiased parameter estimates. In addition, the likelihood-ratio test in the linear mixed model appears to be robust to the considered misspecification in the background covariance structure, given low to moderate phenotypic correlations among siblings. Empirical results show that the inclusion in association analysis of imputed sibling genotypes does not always result in larger test statistic. The actual test statistic may drop in value due to small effect sizes. That is, if the power benefit is small, that the change in distribution of the test statistic under the alternative is relatively small, the probability is greater of obtaining a smaller test statistic. As the genetic effects are typically hypothesized to be small, in practice, the decision on whether family-based imputation could be used as a means to increase power should be informed by prior power calculations and by the consideration of the background correlation.     

Colonic motility diagnosis based on colonic pressure

Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data.     

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.     

Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.