Use of traditional serological methods and oral fluids to assess immunogenicity in children aged 2-16 years after successive annual vaccinations with LAIV.

BACKGROUND: The UK introduced quadrivalent live attenuated influenza vaccine (qLAIV) for children in 2013/2014. The impact of annual vaccination on effectiveness and immunogenicity is being assessed. METHOD: A phase III/IV open-label study of the immunogenicity of annual vaccination with qLAIV (Fluenz™) was conducted over three consecutive years (2014/15-2016/17) in 254, 249 and 162 children respectively. Serum responses to vaccine components were measured by Haemagglutination Inhibition (HAI) and anti-A(H1N1)pdm09 Neuraminidase (NAI) assays, stratified according to previous receipt of AS03B-adjuvanted A(H1N1)pdm09 pandemic vaccine in 2009/10. Antibody levels to the A(H1N1)pdm09 and H3N2 vaccine components in oral fluids (OF) were explored using an ELISA. FINDINGS: More paired pre- and post-vaccination oral fluids (96%) than paired sera (87%) were obtained. Geometric mean titre rises using HAI assays were limited, with maximum rises seen in year one for both influenza B strains when 39% and 43% of subjects seroconverted (95% confidence interval 33-46% and 36-50%, respectively) and year two for influenza H3N2, when 40% (33-46%) individuals seroconverted. Prior pandemic vaccine receipt resulted in higher pre- and post-vaccination A(H1N1)pdm09 HAI titres and lower pre-and post-vaccination NAI (N1 neuraminidase) titres in all three years. OF results were congruent with HAI results; assay specificity compared to HAI was 88.1 and 71.6 percent, and sensitivity was 86.4 and 74.8 percent respectively for A(H1N1)pdm09 and H3N2. CONCLUSION: In all three study years, vaccination with qLAIV resulted in poor antibody responses. However, OFs are an alternative specimen type that allows self sampling, can easily be obtained from children, and their analysis leads to similar conclusions as classic serology by HAI. Their suitability for seroprevalence studies should be investigated. We demonstrated a sustained effect from prior receipt of the AS03B-adjuvanted A(H1N1)pdm09 vaccine, even after repeat vaccination with qLAIV indicating that early exposure to influenza antigens has a significant long lasting effect

Interprofessional communication with hospitalist and consultant physicians in general internal medicine : a qualitative study

This study helps to improve our understanding of the collaborative environment in GIM, comparing the communication styles and strategies of hospitalist and consultant physicians, as well as the experiences of providers working with them. The implications of this research are globally important for understanding how to create opportunities for physicians and their colleagues to meaningfully and consistently participate in interprofessional communication which has been shown to improve patient, provider, and organizational outcomes

Variations in Health Insurance Coverage for Rural and Urban Nonelderly Adult Residents of Florida, Indiana, and Kansas

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72274/1/j.1748-0361.2006.00023.x.pd

DNA polymorphism in the 5′ flanking region of the human carbonic anhydrase II gene on chromosome 8

A restriction-fragment-length polymorphism (RFLP) is described which is associated with the human carbonic anhydrase II gene ( CA2 ) that codes for one of the three genetically distinct carbonic anhydrase isozymes, CA I, CA II, and CA III. The isolated DNA was cleaved with several restriction enzymes and subjected to Southern blot hybridization analysis using a DNA probe containing the 5′ end of the human CA II gene. A two allele RFLP which was detected with the restriction endonuclease, Taq I, is expressed phenotypically on Southern blots as either a 5.4 kilobase (kb) fragment or as 4.0 and 1.4 kb fragments. These fragments result from the presence or absence of a Taq I recognition site in the 5′ flanking region approximately 1.0kb from the initiation codon of the CA II gene. Segregation analysis showed that the alleles are inherited in a Mendelian fashion, with a frequency of 50%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47613/1/439_2004_Article_BF00291652.pd

Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia

<p>Abstract</p> <p>Background</p> <p>Advanced glycation end-products (AGEs) and their receptor (RAGE) occur in dementia of the Alzheimer's type and diabetic microvascular disease. Accumulation of AGEs relates to risk factors for vascular dementia with ageing, including hypertension and diabetes. Cognitive dysfunction in vascular dementia may relate to microvascular disease resembling that in diabetes. We tested if, among people with cerebrovascular disease, (1) those with dementia have higher levels of neuronal and vascular AGEs and (2) if cognitive dysfunction depends on neuronal and/or vascular AGE levels.</p> <p>Methods</p> <p>Brain Sections from 25 cases of the OPTIMA (Oxford Project to Investigate Memory and Ageing) cohort, with varying degrees of cerebrovascular pathology and cognitive dysfunction (but only minimal Alzheimer type pathology) were immunostained for N^<it>ε</it>-(carboxymethyl)-lysine (CML), the most abundant AGE. The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures.</p> <p>Results</p> <p>The probability of cortical neurons staining positive for CML was higher in cases with worse cognition (p = 0.01) or a history of hypertension (p = 0.028). Additionally, vascular CML staining related to cognitive impairment (p = 0.02) and a history of diabetes (p = 0.007). Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002).</p> <p>Conclusion</p> <p>CML staining in cortical neurons and cerebral vessels is related to the severity of cognitive impairment in people with cerebrovascular disease and only minimal Alzheimer pathology. These findings support the possibility that cerebral accumulation of AGEs may contribute to dementia in people with cerebrovascular disease.</p

Benthic and Hyporheic Macroinvertebrate Distribution Within the Heads and Tails of Riffles During Baseflow Conditions

The distribution of lotic fauna is widely acknowledged to be patchy reflecting the interaction between biotic and abiotic factors. In an in-situ field study, the distribution of benthic and hyporheic invertebrates in the heads (downwelling) and tails (upwelling) of riffles were examined during stable baseflow conditions. Riffle heads were found to contain a greater proportion of interstitial fine sediment than riffle tails. Significant differences in the composition of benthic communities were associated with the amount of fine sediment. Riffle tail habitats supported a greater abundance and diversity of invertebrates sensitive to fine sediment such as EPT taxa. Shredder feeding taxa were more abundant in riffle heads suggesting greater availability of organic matter. In contrast, no significant differences in the hyporheic community were recorded between riffle heads and tails. We hypothesise that clogging of hyporheic interstices with fine sediments may have resulted in the homogenization of the invertebrate community by limiting faunal movement into the hyporheic zone at both the riffle head and tail. The results suggest that vertical hydrological exchange significantly influences the distribution of fine sediment and macroinvertebrate communities at the riffle scale

Glycerol monolaurate prevents mucosal SIV transmission

Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection1, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission2–4. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)–rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry5,6. Here we show in this SIV–macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α (also known as CCL20), plasmacytoid dendritic cells and CCR5+ cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4+ T cells to fuel this obligate expansion. We then show that glycerol monolaurate—a widely used antimicrobial compound7with inhibitory activity against the production of MIP-3α and other proinflammatory cytokines8—can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to blockHIV-1 mucosal transmission

A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol

BACKGROUND: Mutations in either of two genes comprising the STSL locus, ATP-binding cassette (ABC)-transporters ABCG5 (encoding sterolin-1) and ABCG8 (encoding sterolin-2), result in sitosterolemia, a rare autosomal recessive disorder of sterol trafficking characterized by increased plasma plant sterol levels. Based upon the genetics of sitosterolemia, ABCG5/sterolin-1 and ABCG8/sterolin-2 are hypothesized to function as obligate heterodimers. No phenotypic difference has yet been described in humans with complete defects in either ABCG5 or ABCG8. These proteins, based upon the defects in humans, are responsible for regulating dietary sterol entry and biliary sterol secretion. METHODS: In order to mimic the human disease, we created, by a targeted disruption, a mouse model of sitosterolemia resulting in Abcg8/sterolin-2 deficiency alone. Homozygous knockout mice are viable and exhibit sitosterolemia. RESULTS: Mice deficient in Abcg8 have significantly increased plasma and tissue plant sterol levels (sitosterol and campesterol) consistent with sitosterolemia. Interestingly, Abcg5/sterolin-1 was expressed in both liver and intestine in Abcg8/sterolin-2 deficient mice and continued to show an apical expression. Remarkably, Abcg8 deficient mice had an impaired ability to secrete cholesterol into bile, but still maintained the ability to secrete sitosterol. We also report an intermediate phenotype in the heterozygous Abcg8+/- mice that are not sitosterolemic, but have a decreased level of biliary sterol secretion relative to wild-type mice. CONCLUSION: These data indicate that Abcg8/sterolin-2 is necessary for biliary sterol secretion and that loss of Abcg8/sterolin-2 has a more profound effect upon biliary cholesterol secretion than sitosterol. Since biliary sitosterol secretion is preserved, although not elevated in the sitosterolemic mice, this observation suggests that mechanisms other than by Abcg8/sterolin-2 may be responsible for its secretion into bile