Immunopathogenesis of canine atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disease commonly seen in dogs and humans. Most cases involve hypersensitivity to the house dust mites Dertnatophagoides farinae and D. pteronyssinus. This study has shown that Dermatophagoides specific IgE and peripheral blood mononuclear cell (PBMC) responses were largely restricted to skin test positive atopic dogs. Furthermore, immunoblotting and PBMC proliferation studies demonstrated that the major target of immune recognition is a 98/104kD protein, rather than the low molecular weight group 1 and 2 proteins important in humans. The close association between serological findings and PBMC proliferation implies that T-cells participate in the pathogenesis of canine AD by supporting IgE production. Human AD is associated with T-helper 2 (TH2) type responses, although THi cytokines are present in chronic lesions. In contrast, tolerance in healthy individuals is mediated by regulatory T-cells. Using semi-quantitative reverse transcriptase-polymerase chain reactions, this study found that canine AD is associated with over-production of the TH2 cytokine interleukin (IL)-4, whilst tolerance in healthy individuals is associated with the immuno-suppressive cytokines transforming growth factor beta and EL-10. Higher levels of the THi cytokines interferon gamma, tumour necrosis factor alpha and IL-2 seen in lesional compared to non-lesional and healthy skin could be induced by subsequent self-trauma and secondary infections. These results characterise the first spontaneously occurring animal model of human AD

The performance of HIV rapid antibody detection assays in children

Background: HIV rapid antibody assays are important for screening children aged 98%. Seroreversion rates were lowest with the Determine rapid test. Three HIV rapid tests (Abon, Advanced Quality, Determine) detected 100% of HIV-infected children <18 months of age, the Reveal, SD Bioline and Insti rapid tests missed 27 (41.5%), 1 (4.5%) and 1 (1.5%) of the HIV-infected children respectively. In children ≥ 18 months of age, sensitivity of rapid tests for detecting HIV infection ranged from 69.2% to 100% and specificity of all rapid tests was 100%. Conclusions: None of the 6 HIV rapid tests evaluated achieved both the World Health Organisation recommended sensitivity and specificity standards for any antibody assay used in screening for HIV exposure in children <18 months. The Determine test showed the best overall diagnostic accuracy and is therefore recommended as the preferred screening test for children. Recommendations: on the use of specific HIV rapid tests in infants and young children should be based on evaluation of their performance in the population to be tested

HIV-infected infants born to women who tested HIV-negative during pregnancy

The prevention of mother-to-child transmission (PMTCT) programme in the Western Cape is said to have achieved 100% coverage.1 This implies that all pregnant women who attend an antenatal health care facility in the public sector are offered voluntary counselling and testing (VCT). Uptake varies but has been reported to be as high as 90% in the Guguletu district.1 Currently, women who test HIV-positive qualify for the nevirapine-based PMTCT programme. Transmission rates below 10% have been achieved in some health districts (Médecins sans Frontières — unpublished research). Mothers of several perinatally infected infants recently diagnosed in our institution have indicated that they tested HIV-negative during their pregnancy. In some cases we have verified their statements with clinical and laboratory documentation. There is a need to determine the frequency of this phenonomen. Pregnant women are encouraged to book at their nearest antenatal clinic before 5 months’ gestation, although this frequently does not occur. We are concerned about women who do book early and test HIV-negative. Some may be in the ‘window period’ of the infection or become infected from a sexual partner during the latter stages of pregnancy. At present, there is no provision within the PMTCT programme for repeat HIV testing during pregnancy. Some women may, therefore, be denied the benefits of prevention measures including counselling on infant feeding options

Preparing Students for the Environment of the Practice of Consulting Engineer

In the United States of America, the body of knowledge required for an individual to be allowed to take the engineering licensing examination, which on passing allows the individual to be in responsible charge of engineering projects, is usually defined by laws and regulations of each state. In California, the shortest path taken by most individuals is one where the individual graduates from an ABET accredited undergraduate program; passes the Engineer in Training (EIT) examination and works under the supervision of a licensed engineer for two years (one year if the individual has a Masters degree in relevant field). In order to better prepare the student to enter the practice of engineering, and thus give the student an immediate level of comfort with the real world environment, practical design needs to be directly incorporated into the teaching of design. This paper presents teaching methods used to teach undergraduate architectural engineering design courses, where the discipline of concentration is structural engineering. The format used exposes the students to instructors that are current consulting engineers and to courses that are modeled in line with the structural engineering profession. The theory, of construction materials (concrete, steel, masonry and timber) is covered for each material at element level in a lecture format. Design using the materials at a system level (building) is then taught in a laboratory format. In this later format, the students prepare complete construction documents (structural calculations, structural plans and structural specifications) for real projects using architectural plans. This “learn by doing” format has proven-over time-to prepare the students to the same environment that the students face after graduation. It is generally an accepted fact in the structural profession in California that, graduates from Architectural Engineering program (ARCE) at California Polytechnic State University (CAL POLY) “hit the ground running from day one”. This is attributed to the familiarity, of the design office environment, obtained during their undergraduate education. The familiarity is acquired through the design laboratories taught by design professionals

BCG Vaccination in HIV-Infected Children

Despite the use of Bacillus Calmette-Guérin (BCG) vaccination for many years, infants and young children exposed to adults with infectious forms of tuberculosis (TB) are at high risk of developing complicated TB disease. This risk is much higher among HIV-infected children, and data on BCG protective efficacy in HIV-infected children is lacking. Recent research on BCG safety in HIV-infected infants has resulted in policy shifts, but implementation is challenging. New approaches to preventing TB among infants and children, particularly HIV-infected infants, are needed. This paper briefly reviews BCG safety and efficacy considerations in HIV-infected infants and discusses other approaches to preventing TB, including new TB vaccines and vaccination strategies

Expression, intracellular targeting and purification of HIV Nef variants in tobacco cells

Background Plants may represent excellent alternatives to classical heterologous protein expression systems, especially for the production of biopharmaceuticals and vaccine components. Modern vaccines are becoming increasingly complex, with the incorporation of multiple antigens. Approaches towards developing an HIV vaccine appear to confirm this, with a combination of candidate antigens. Among these, HIV-Nef is considered a promising target for vaccine development because immune responses directed against this viral protein could help to control the initial steps of viral infection and to reduce viral loads and spreading. Two isoforms of Nef protein can be found in cells: a full-length N-terminal myristoylated form (p27, 27 kDa) and a truncated form (p25, 25 kDa). Here we report the expression and purification of HIV Nef from transgenic tobacco. Results We designed constructs to direct the expression of p25 and p27 Nef to either the cytosol or the secretory pathway. We tested these constructs by transient expression in tobacco protoplasts. Cytosolic Nef polypeptides are correctly synthesised and are stable. The same is not true for Nef polypeptides targeted to the secretory pathway by virtue of a signal peptide. We therefore generated transgenic plants expressing cytosolic, full length or truncated Nef. Expression levels were variable, but in some lines they averaged 0.7% of total soluble proteins. Hexahistidine-tagged Nef was easily purified from transgenic tissue in a one-step procedure. Conclusion We have shown that transient expression can help to rapidly determine the best cellular compartment for accumulation of a recombinant protein. We have successfully expressed HIV Nef polypeptides in the cytosol of transgenic tobacco plants. The proteins can easily be purified from transgenic tissue

Interdisciplinary capstone design: Architects, structural engineers, and construction managers

The College of Architecture and Environmental Design at California Polytechnic State University in San Luis Obispo is the only college in the nation that has departments of Architecture, Architectural Engineering, Construction Management and Landscape Architecture in the same college. The institution has a 60 year tradition of collaboration between the engineering, architecture and construction disciplines, particularly at the lower division level. To enhance this collaboration, the college committed to providing an upper division, interdisciplinary experience to every student in the form of a project based, team oriented five unit studio laboratory that every student would take. The course is now in its third year and requires small teams of architecture, engineering, construction and landscape architecture students to complete the schematic level design of an actual building for a real client. The challenges in creating and executing such a course fall into three major areas: institutional, logistical and pedagogical. Institutional issues include university support and concurrence from four different department heads. Logistical issues range from finding open time within the four schedules to offer the course and securing physical locations for small and large group meeting areas to the seemingly mundane tasks of ensuring all students are in the correct location and finding common times for the instructors to meet. Pedagogically, the course needs a unified and integrated approach that must be agreed to and implemented by all professors. Traditionally professors work as individuals and team teaching of this magnitude is a paradigm shift that requires significant time, a flexible mindset and a commitment to collaborate. This paper reports on the progress of this course using survey assessment data and direct performance indicators. These same data provide valuable support to the 3 a-k ABET program criteria. The variety of projects undertaken to date illustrates the flexibility of this course. The paper describes how the challenges listed above have been overcome particularly concerning the role of the faculty in the course and the merging of very different department cultures. Finally, the future of the course and the suggested improvements are highlighted

Epidemiology of Staphylococcus aureus bacteraemia at a tertiary children's hospital in Cape Town, South Africa

BACKGROUND: Staphylococcus aureus is an important pathogen in paediatric patients with bloodstream infections. The epidemiology of S. aureus bacteraemia, however, has not been well documented in children in South Africa. METHODS: A retrospective study was conducted at a children's hospital in Cape Town, South Africa, to investigate the epidemiology of S. aureus bacteraemia from 2007-2011. The incidence, clinical presentation, risk factors, management and outcomes of methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) bacteraemia were compared. RESULTS: Over the five year study period, 365 episodes of S. aureus bacteraemia were identified. The annual incidence was 3.28 cases per 1000 hospital admissions. MRSA was responsible for 26% of S. aureus bacteraemia and 72% of nosocomial infections. Only six possible cases of community-acquired MRSA infections were described. MSSA bacteraemia was more likely to present as pulmonary and bone or joint infections, while bacteraemia without a source was the most common presentation with MRSA.  Infants, children with malnutrition, and residents of long-term care facilities were at highest risk for MRSA bacteraemia. The overall case fatality rate for S. aureus bacteraemia was 8.8% over five years, with MRSA being the only significant risk factor for mortality. CONCLUSION: The incidence of S. aureus bacteraemia and MRSA bacteraemia in children has remained stable over the past five years. MRSA is a predominantly nosocomial pathogen in children with S. aureus bacteraemia in Cape Town, South Africa

The c-terminal extension of a hybrid immunoglobulin A/G heavy chain is responsible for its Golgi-mediated sorting to the vacuole

We have assessed the ability of the plant secretory pathway to handle the expression of complex heterologous proteins by investigating the fate of a hybrid immunoglobulin A/G in tobacco cells. Although plant cells can express large amounts of the antibody, a relevant proportion is normally lost to vacuolar sorting and degradation. Here we show that the synthesis of high amounts of IgA/G does not impose stress on the plant secretory pathway. Plant cells can assemble antibody chains with high efficiency and vacuolar transport occurs only after the assembled immunoglobulins have traveled through the Golgi complex. We prove that vacuolar delivery of IgA/G depends on the presence of a cryptic sorting signal in the tailpiece of the IgA/G heavy chain. We also show that unassembled light chains are efficiently secreted as monomers by the plant secretory pathway

Presentation and Outcome of Tuberculous Meningitis among Children: Experiences from a Tertiary Children’s Hospital

Background: Diagnosis of tuberculous meningitis (TBM) is complicated and outcome is poor especially in resource limited settings. Early diagnosis and prompt treatment are vital in effective treatment. We set out to describe experiences in the management and immediate outcome of TBM a tertiary-level children’s hospital in a high HIV and tuberculosis co-infection setting. Methods: This retrospective study included children who were diagnosed with TBM in the year 2009. A pre-coded questionnaire was used to extract data on presentation, diagnostics, treatment and outcome at the time of hospital discharge. Data was analyzed using STATA statistical package (StataCorp, Version 11). Results: Of the 40 children diagnosed with TBM, 6 (15%) had definitive TBM, 17 (42.5%) had probable TBM and 17 (42.5%) had possible TBM. The cerebrospinal fluid (CSF) chemistry and cells were abnormal in 39/40 (98%). Mantoux test was reactive in 16/29 (55%) and 17/30 (57%) had Chest X-rays suggestive of tuberculosis. Only 3/21 (14%) had positive sputum tuberculosis culture and 89% (32/36) had neuro-imaging abnormalities. Outcome at discharge was; 8% died, 49% improved with neurological sequelae and 43% improved without sequelae. Having TBM stage 3 at admission was associated with mortality (p=0.001). Conclusions: Most children had early diagnosis of TBM and mortality was lower than previous studies. We recommend a larger prospective study to further understand the outcome of TBM.Keywords: Tuberculous meningitis, children, presentation, outcome, AfricaAfrican Health sciences Vol 14 No. 1 March 201