Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β\u3csub\u3e2\u3c/sub\u3e-agonist use

Background Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this brake on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion. Methods Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination. Results Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP. Conclusion Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased phosphorylation does not appear to be associated with a particular β2-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair

Autism and the U.K. secondary school experience

This research investigated the self-reported mainstream school experiences of those diagnosed on the autistic spectrum compared with the typically developing school population. Existing literature identifies four key areas that affect the quality of the school experience for students with autism: social skills, perceived relationships with teaching staff, general school functioning, and interpersonal strengths of the young person. These areas were explored in a mainstream U.K. secondary school with 14 students with autism and 14 age and gender matched students without autism, using self-report questionnaires and semi-structured interviews. Quantitative analyses showed consistent school experiences for both groups, although content analysis of interview data highlighted some differences in the ways in which the groups perceive group work, peers, and teaching staff within school. Implications for school inclusion are discussed, drawing attention to how staff awareness of autism could improve school experience and success for students with autism attending mainstream schools

"Am iz kwiin" (I'm his queen): Combining interpretative phenomenological analysis with a feminist approach to work with gems in a resource-constrained setting

This article focuses on working with gems using a feminist approach to interpretative phenomenological analysis (IPA) in a resource-constrained setting. The research explores the experiences of maternal disclosure of HIV to children of HIV positive mothers in Kingston, Jamaica. A feminist approach helps recognise power imbalances within research relationships and the women’s lived experiences. We present three “gems” which illuminate women’s lived experiences and explore how popularised representations of women’s sexuality and mothering influence disclosure discourses. We use emotion work as a conceptual resource to structure the women’s narratives and challenge existing policy discourses, which arguably represent disclosure within a binary, rationalist, decision-making framework. This article adds to global literature on maternal HIV disclosure and problematises policy discourses by bringing into relief the emotion work women engage in when deciding if and how to communicate their HIV status to their children. It adds to the body of research using IPA, particularly in resource-constrained settings where IPA has thus far had little application

Perioperative donor bone marrow infusion augments chimerism in heart and lung transplant recipients

Background.: We and others have demonstrated that a low level of donor cell chimerism was present for years after transplantation in tissues and peripheral blood of heart and lung recipients; it was associated, in the latter, with a lower incidence of chronic rejection. To augment this phenomenon, we initiated a trial combining simultaneous infusion of donor bone marrow with heart or lung allotransplantation. Methods.: Between September 1993 and January 1995, 15 nonconditioned patients received either heart (n = 10) or lung (n = 5) allografts concurrently with an infusion of unmodified donor bone marrow (3.0 × 108 cells/kg), and were maintained on an immunosuppressive regimen consisting of tacrolimus and steroids. Results.: There was no complication associated with the infusion of donor bone marrow. Chimerism was detectable in 73% of bone marrow-augmented patients up to the last sample tested. Of the 5 control recipients who did not receive bone marrow infusion, only 1 had detectable chimerism by flow on postoperative day 15, which dwindled to an undetectable level by postoperative day 36. None of the patients had evidence of donor-specific immune modulation by mixed lymphocyte reaction. Conclusions.: The combined infusion of donor bone marrow and heart or lung transplantation, without preconditioning of the recipient, is safe and is associated with an augmentation of donor cell chimerism. © 1995 The Society of Thoracic Surgeons

Elimination of mother-to-child transmission of HIV in South Africa : rapid scale-up using quality improvement

BACKGROUND. South Africa (SA) is committed to achieving the goal of eliminating mother-to-child transmission (MTCT) of HIV by 2015. To achieve this, universal coverage of quality antenatal, labour, delivery and postnatal services for all women has to be attained. Over the past decade, the prevention of mother-to-child transmission (PMTCT) programme has been scaled up to reach all healthcare facilities in the country. However, challenges persist in achieving 100% coverage and access to the programme. OBJECTIVES. We describe the process undertaken by the National Department of Health (NDoH), in collaboration with partners, to develop, implement and monitor a data-driven intervention to improve facility, district, provincial and national PMTCT-related performance. METHODS. Between 2011 and 2013, the NDoH developed and implemented an intervention using data-driven participatory processes to understand facility-level bottlenecks to optimise PMTCT implementation and to scale up priority PMTCT actions nationally. RESULTS. There was remarkable improvement across all key indicators in the PMTCT cascade over the 3 years 2011 - 2013. Simple monitoring tools such as a visual dashboard and data for action reports were successfully used to improve the performance of the PMTCT programme across SA. MTCT has shown a significant downward trend. CONCLUSIONS. It is feasible to implement district-level, data-driven quality improvement processes at a national scale to improve the performance of the PMTCT programme at the local level.http://www.samj.org.zaam201

Identification of Arhgef12 and Prkci as genetic modifiers of retinal dysplasia in the Crb1rd8 mouse model.

Mutations in the apicobasal polarity gene CRB1 lead to diverse retinal diseases, such as Leber congenital amaurosis, cone-rod dystrophy, retinitis pigmentosa (with and without Coats-like vasculopathy), foveal retinoschisis, macular dystrophy, and pigmented paravenous chorioretinal atrophy. Limited correlation between disease phenotypes and CRB1 alleles, and evidence that patients sharing the same alleles often present with different disease features, suggest that genetic modifiers contribute to clinical variation. Similarly, the retinal phenotype of mice bearing the Crb1 retinal degeneration 8 (rd8) allele varies with genetic background. Here, we initiated a sensitized chemical mutagenesis screen in B6.Cg-Crb1rd8/Pjn, a strain with a mild clinical presentation, to identify genetic modifiers that cause a more severe disease phenotype. Two models from this screen, Tvrm266 and Tvrm323, exhibited increased retinal dysplasia. Genetic mapping with high-throughput exome and candidate-gene sequencing identified causative mutations in Arhgef12 and Prkci, respectively. Epistasis analysis of both strains indicated that the increased dysplastic phenotype required homozygosity of the Crb1rd8 allele. Retinal dysplastic lesions in Tvrm266 mice were smaller and caused less photoreceptor degeneration than those in Tvrm323 mice, which developed an early, large diffuse lesion phenotype. At one month of age, Müller glia and microglia mislocalization at dysplastic lesions in both modifier strains was similar to that in B6.Cg-Crb1rd8/Pjn mice but photoreceptor cell mislocalization was more extensive. External limiting membrane disruption was comparable in Tvrm266 and B6.Cg-Crb1rd8/Pjn mice but milder in Tvrm323 mice. Immunohistological analysis of mice at postnatal day 0 indicated a normal distribution of mitotic cells in Tvrm266 and Tvrm323 mice, suggesting normal early development. Aberrant electroretinography responses were observed in both models but functional decline was significant only in Tvrm323 mice. These results identify Arhgef12 and Prkci as modifier genes that differentially shape Crb1-associated retinal disease, which may be relevant to understanding clinical variability and underlying disease mechanisms in humans

Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections

During the past year, a group has argued that unsafe injections are a major if not the main mode of HIV-1 transmission\ud in sub-Saharan Africa. We review the main arguments used to question the epidemiological interpretations on the lead\ud role of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence that unsafe injections are a\ud predominant mode of HIV-1 transmission in sub-Saharan Africa. Conversely, though there is a clear need to eliminate\ud all unsafe injections, epidemiological evidence indicates that sexual transmission continues to be by far the major\ud mode of spread of HIV-1 in the region. Increased efforts are needed to reduce sexual transmission of HIV-1