Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA,factor H binding protein,Neisseria heparin-binding antigen and Neisseria adhesin A)

BACKGROUND:Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB.OBJECTIVE:To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine.METHODS:Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated.RESULTS:The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD.CONCLUSION:From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.     

Mediation of platelet adhesion to fibrillar collagen in flowing blood by a proteolytic fragment of human von Willebrand factor

The effect of purified von Willebrand Factor (vWF) fragments, SpII (dimer of two 110 kd subunits) and SpIII (dimer of two 170 kd subunits) obtained with S aureus V-8 protease was tested upon platelet adhesion to collagen. Purified fibrillar human collagen coated onto cover slips was incubated with SpII, SpIII, or undigested vWF and exposed to reconstituted human blood in a parallel-plate perfusion chamber at a high shear rate. Platelet-collagen interactions were estimated using 51Cr-platelets and quantitative morphometry. When blood was reconstituted with citrated autologous plasma, SpIII and vWF strikingly enhanced platelet adhesion to collagen whereas SpII had no effect. When blood was reconstituted with human albumin and divalent cations, SpIII and vWF again promoted platelet adhesion to collagen. In conclusion, our data suggest that (1) SpIII, the N-terminal portion of vWF which binds to platelet membrane glycoprotein Ib, functionally substitutes for vWF in supporting platelet adhesion to collagen; (2) SpII, the C- terminal portion which binds to glycoprotein IIb/IIIa, has no such effect; (3) in addition to its platelet binding domain, SpIII contains another site for binding to collagen; and (4) the multimeric structure of vWF is not required for platelet adhesion to collagen.     

Genetic and environmental contributions to the relationship between education and anxiety disorders - a twin study

Tambs K, Kendler KS, Reichborn‐Kjennerud T, Aggen SH, Harris JR, Neale MC, Hettema JM, Sundet JM, Battaglia M, Røysamb E. Genetic and environmental contributions to the relationship between education and anxiety disorders – a twin study. Objective: To examine the negative statistical relationship between educational level and risk of anxiety disorders, and to estimate to what extent this relationship may be explained by genes or environmental factors influencing both phenotypes. Method: Registry data on educational level for 3339 young adult Norwegian twin pairs and diagnostic data on anxiety disorders for 1385 of these pairs were analysed, specifying structural equations models using MX software. Results: In the best‐fitting model, genes accounted for 59% of the variance in education. 18% of the variance was due to environmental factors shared by co‐twins, and the remaining 23% due to non‐shared environment; 46% of the variance in liability to anxiety disorders was genetic, the remaining variance was due to non‐shared environment. A phenotypic polychoric correlation of ?0.30 between educational level and ‘any anxiety disorder’ was estimated to be primarily (83% in the best‐fitting model) caused by genes common to the two traits. Conclusion: The relationship between low education and risk of anxiety disorders appears to be primarily determined by genetic effect common to educational level and anxiety disorders.     

Panic syndromes in a population-based sample of male and female twins

BACKGROUND: The risk for panic disorder (PD) is substantially increased in relatives of probands with PD. Prior literature provides only limited information about the degree to which this increase is due to genetic factors or family environment. METHODS: In personal interviews with both members of 3194 twin pairs, we assessed the lifetime history of lifetime panic attacks and PD. Twin resemblance was assessed by tetrachoric correlation and single and multiple threshold biometrical model fitting. RESULTS: As fully syndromal PD, by DSM-III-R criteria, was too rare to analyse usefully we examined four other dichotomous definitions of increasing stringency: panic probe and very broad, broad and intermediate PD. For all four definitions and for the multiple threshold analyses, the best-fit model indicated that twin resemblance was due solely to genetic factors with a moderate heritability (33-43%). For the broad and intermediate dichotomous definitions of PD, however, a model with twin resemblance due to familial-environmental factors fit nearly as well. No gender effects were seen on the genetic risk factors for these PD-like syndromes. CONCLUSION: Even with large epidemiological samples of twins, studying disorders as uncommon as PD is problematical. Despite these difficulties, our results suggest that: (i) narrowly and broadly defined PD are probably on the same continuum of liability; (ii) twin resemblance for these PD-like syndromes is likely due largely to genetic factors with a moderate level of heritability although a contribution of familial-environmental factors cannot be excluded, and, (iii) the same familial risk factors impact. to a similar degree, on the liability to PD in males and females.     

An association study of DRD5 with smoking initiation and progression to nicotine dependence

A large body of genetic epidemiological data strongly implicate genetic factors in the etiology of smoking behavior. Polymorphisms of genes in the dopaminergic system are plausible functional candidate genes and a linkage and an association study suggested that the type 5 dopamine receptor gene (DRD5) may be etiologically involved. We investigated the association of four DRD5 polymorphisms with smoking initiation and progression to nicotine dependence in a population-based sample of over 900 subjects. For smoking initiation, there was no significant association with the four DRD5 markers we studied; however, maximum likelihood analyses suggested the presence of a haplotype protective against smoking initiation. For progression to nicotine dependence, there were no strongly significant associations with the four DRD5 markers or for the estimated haplotypes. These data are not consistent with a strong etiological role for DRD5 in the etiology of these complex smoking behaviors.     

Sex Differences in the Sources of Genetic Liability to Alcohol Abuse and Dependence in a Population-Based Sample of U.S. Twins

BACKGROUND: There are substantial sex differences in all levels of alcohol involvement among U.S. adults. The goal of this study was to test whether the magnitude and sources of genetic and environmental influences on liability for alcohol abuse and dependence differ for men and women. METHODS: Structured personal interviews were used to assess DSM-III-R- and DSM-IV-defined alcohol abuse and dependence among 5091 male and 4168 female twins (including 1546 identical, 1128 same-sex fraternal, and 1423 opposite-sex pairs) born in Virginia between 1934 and 1974. Twin correlations were analyzed using structural equation modeling. RESULTS: The magnitude of twin-pair resemblance was similar across several definitions of alcoholism and was substantially higher among identical than fraternal pairs. The proportion of population variation in liability attributed to genetic factors was substantial among both women (55-66%) and men (51-56%), and we found little evidence of a role of environmental factors shared by family members. In all definitions studied, we could reject a model that the genetic sources of liability in the two sexes overlap completely. CONCLUSION: In this first population-based study of alcoholism among male and female twins from the U.S., we found that genetic factors play a major role in the development of alcoholism in both sexes, that the magnitudes of genetic influence were equally high for men and women, and that the genetic sources of vulnerability are partially, but not completely, overlapping in men and women.     

Radiological imaging of a massive dermoid in the male pelvis

A dermold cyst, arising from the posterior aspects of the prostate and seminal vesicles, and extending into the pelvis to masquerade as a full bladder, must be exceedingly rare. Ultrasound, computed tomography and especially magnetic resonance imaging (MRI) proved to be invaluable in making the diagnosis, and MRI in particular was very useful in providing an anatomical road map for surgery.