Comparison of screening strategies to improve the diagnosis of latent tuberculosis infection in the HIV-positive population: a cohort study

Background HIV is the most important risk factor for progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB). Detection and treatment of LTBI is necessary to reduce the increasing burden of TB in the UK, but a unified LTBI screening approach has not been adopted. Objective To compare the effectiveness of a TB risk-focused approach to LTBI screening in the HIV-positive population against current UK National Institute for Health and Clinical Excellence (NICE) guidance. Design Prospective cohort study. Setting Two urban HIV treatment centres in London, UK. Participants 114 HIV-infected individuals with defined TB risk factors were enrolled prospectively as part of ongoing studies into HIV and TB co-infection. Outcome measures The yield and case detection rate of LTBI cases within the research study were compared with those generated by the NICE criteria. Results 17/114 (14.9%, 95% CI 8.3 to 21.5) had evidence of LTBI. Limiting screening to those meeting NICE criteria for the general population (n=43) would have detected just over half of these, 9/43 (20.9%, 95% CI 8.3 to 33.5) and those meeting criteria for HIV co-infection (n=74) would only have captured 8/74(10.8%, 95% CI 3.6 to 18.1) cases. The case detection rates from the study and NICE approaches were not significantly different. LTBI was associated with the presence of multiple TB risk factors (p=0.002). Conclusion Adoption of a TB risk-focused screening algorithm that does not use CD4 count stratification could prevent more cases of TB reactivation, without changing the case detection rate. These findings should be used to inform a large-scale study to create unified guidelines

Comparative expression of mouse and chicken shisa homologues during early development

During vertebrate embryogenesis, fibroblast growth factor (FGF) and Wnt signaling have been implicated in diverse cellular processes, including cell growth, differentiation, and tissue patterning. The recently identified Xenopus Shisa protein promotes head formation by inhibiting Wnt and FGF signaling through its interaction with the immature forms of Frizzled and FGF receptors in the endoplasmic reticulum, which prevents their posttranslational maturation. Here, we describe the mouse and chicken homologues of Xenopus Shisa. The mouse and chicken Shisa proteins share, respectively, 33.6% and 33.8% identity with the Xenopus homolog. In situ hybridization analysis shows that mouse shisa is expressed throughout embryonic development, predominantly in the anterior visceral endoderm, headfolds, somites, forebrain, optic vesicle, and limb buds. Cross-species comparison shows that the expression pattern of cshisa closely mirrors that of mshisa. Our observations indicate that the Shisa family genes are typically expressed in tissues known to require the modulation of Wnt and FGF signaling. Developmental Dynamics 235:2567-2573, 2006. (c) 2006 Wiley-Liss, Inc

ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans

SummaryMycobacterium tuberculosis-induced cellular aggregation is essential for granuloma formation and may assist establishment and early spread of M. tuberculosis infection. The M. tuberculosis ESX1 mutant, which has a non-functional type VII secretion system, induced significantly less production of the host macrophage-derived chemokine fractalkine (CX3CL1). Upon infection of human macrophages ESX1-dependent fractalkine production mediated selective recruitment of CD11b+ monocytic cells and increased infection of neighbouring cells consistent with early local spread of infection. Fractalkine levels were raised in vivo at tuberculous disease sites in humans and were significantly associated with increased CD11b+ monocytic cellular recruitment and extent of granulomatous disease. These findings suggest a novel fractalkine-dependent ESX1-mediated mechanism in early tuberculous disease pathogenesis in humans. Modulation of M. tuberculosis-mediated fractalkine induction may represent a potential treatment option in the future, perhaps allowing us to switch off a key mechanism required by the pathogen to spread between cells

Characterization and Control of the Microbial Community Affiliated with Copper or Aluminum Heat Exchangers of HVAC Systems

Microbial growth in heating ventilation and air-conditioning (HVAC) systems with the subsequent contamination of indoor air is of increasing concern. Microbes and the subsequent biofilms grow easily within heat exchangers. A comparative study where heat exchangers fabricated from antimicrobial copper were evaluated for their ability to limit microbial growth was conducted using a full-scale HVAC system under conditions of normal flow rates using single-pass outside air. Resident bacterial and fungal populations were quantitatively assessed by removing triplicate sets of coupons from each exchanger commencing the fourth week after their installation for the next 30 weeks. The intrinsic biofilm associated with each coupon was extracted and characterized using selective and differential media. The predominant organisms isolated from aluminum exchangers were species of Methylobacterium of which at least three colony morphologies and 11 distinct PFGE patterns we found; of the few bacteria isolated from the copper exchangers, the majority were species of Bacillus. The concentrations and type of bacteria recovered from the control, aluminum, exchangers were found to be dependent on the type of plating media used and were 11,411–47,257 CFU cm−2 per coupon surface. The concentration of fungi was found to average 378 CFU cm−2. Significantly lower concentrations of bacteria, 3 CFU cm−2, and fungi, 1 CFU cm−2, were recovered from copper exchangers regardless of the plating media used. Commonly used aluminum heat exchangers developed stable, mixed, bacterial/fungal biofilms in excess of 47,000 organisms per cm2 within 4 weeks of operation, whereas the antimicrobial properties of metallic copper were able to limit the microbial load affiliated with the copper heat exchangers to levels 99.97 % lower during the same time period

T-cell immunophenotyping distinguishes active from latent tuberculosis.

BACKGROUND: Changes in the phenotype and function of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4+ and CD8+ T-cell subsets in response to stage of infection may allow discrimination between active tuberculosis and latent tuberculosis infection. METHODS: A prospective comparison of M. tuberculosis-specific cellular immunity in subjects with active tuberculosis and latent tuberculosis infection, with and without human immunodeficiency virus (HIV) coinfection. Polychromatic flow cytometry was used to measure CD4+ and CD8+ T-cell subset phenotype and secretion of interferon γ (IFN-γ), interleukin 2 (IL-2), and tumor necrosis factor α (TNF-α). RESULTS: Frequencies of CD4+ and CD8+ cells secreting IFN-γ-only, TNF-α-only and dual IFN-γ/TNF-α were greater in active tuberculosis vs latent tuberculosis infection. All M. tuberculosis-specific CD4+ subsets, with the exception of IL-2-only cells, switched from central to effector memory phenotype in active tuberculosis vs latent tuberculosis infection, accompanied by a reduction in IL-7 receptor α (CD127) expression. The frequency of PPDspecific CD4+ TNF-α-only-secreting T cells with an effector phenotype accurately distinguished active tuberculosis from latent tuberculosis infection with an area under the curve of 0.99, substantially more discriminatory than measurement of function alone. CONCLUSIONS: Combined measurement of T-cell phenotype and function defines a highly discriminatory biomarker of tuberculosis disease activity. Unlocking the diagnostic and monitoring potential of this combined approach now requires validation in large-scale prospective studies

How to Measure Procedural Knowledge for Solving Biodiversity and Climate Change Challenges

To cope with biodiversity and climate change challenges, Education for Sustainable Development (ESD) needs to emphasize knowledge that considers multiple perspectives. Optimizing teacher education requires knowledge about the prerequisites of student teachers. The latter includes content knowledge with respect to Sustainable Development (SD). Apart from situational and conceptual knowledge, procedural knowledge (containing solution strategies) is of special interest, but it is much more difficult to measure. Thus, this study aims at developing a refined procedure to measure SD-relevant procedural knowledge and to define a measure for such knowledge, including a suitable benchmark for its evaluation. As SD-relevant knowledge, the SD challenges biodiversity loss and climate change were focused on. For operationalizing these challenges, the highly relevant contexts insects and pollination and peatland use were chosen. For both SD challenges and contexts, potential solution strategies were identified by a literature review. A procedure was then tested to measure procedural knowledge. The procedure includes a two-round expert survey (Delphi approach) with an in-between think-aloud study with student teachers. The described innovative procedure resulted in a measure (18 items) to assess procedural knowledge of student teachers via effectiveness estimations of provided solution strategies. This measure contains procedural knowledge items that are related to prior presented scenarios regarding the two contexts and a benchmark to evaluate these items. The benchmark derives from the second round of the Delphi study. The procedure and the developed final instrument include expertise from multiple disciplines such as ESD, SD, biodiversity, insect and pollination, climate change and peatland use. The sophisticated procedure can be transferred to challenging measurement developments. Furthermore, the measure provided for SD-relevant knowledge can be applied to other target groups in upper secondary and in higher education within ESD

Subcutaneous fat necrosis in neonates with hypoxic ischaemic encephalopathy registered in the Swiss National Asphyxia and Cooling Register

BACKGROUND Neonates with hypoxic ischaemic encephalopathy (HIE) are routinely treated with therapeutic hypothermia (TH) for 72 h in order to improve neurological outcome. Subcutaneous fat necrosis (SCFN) is an adverse event occurring in neonates with HIE. METHODS We analyzed risk factors for SCFN regarding demographic factors, cooling methods and deviation from target temperature range during hypothermia therapy. Data of all neonates registered in the National Asphyxia and Cooling Register in Switzerland between 2011 and 2013 were analyzed. RESULTS 2.8 % of all cooled neonates with HIE developed SCFN. Perinatal and neonatal characteristics did not differ between neonates with and without SCFN. Applied cooling methods did not correlate with the occurrence of SCFN. In neonates with SCFN 83.3 % of all noted temperatures were within the target temperature range versus 77.5 % in neonates without SCFN. Neonates with SCFN showed 3.6 % of all measured temperatures below target temperature range compared to 12.7 % in neonates without SCFN. CONCLUSION Subcutaneous fat necrosis in the neonate with HIE undergoing TH is a potential adverse event that seems to occur independently from the whole-body cooling method applied and proportion of temperature measurements outside target temperature range. In this cohort, moderate overcooling associated with moderate hypothermia (33.0-34.0 °C) does not seem to be an independent risk factor for SCFN. There is no correlation between the severity of HIE and incidence of SCFN

The Metal Permease ZupT from Escherichia coli Is a Transporter with a Broad Substrate Spectrum

The Escherichia coli zupT (formerly ygiE) gene encodes a cytoplasmic membrane protein (ZupT) related to members of the eukaryotic ZIP family of divalent metal ion transporters. Previously, ZupT was shown to be responsible for uptake of zinc. In this study, we show that ZupT is a divalent metal cation transporter of broad substrate specificity. An E. coli strain with a disruption in all known iron uptake systems could grow in the presence of chelators only if zupT was expressed. Heterologous expression of Arabidopsis thaliana ZIP1 could also alleviate iron deficiency in this E. coli strain, as could expression of indigenous mntH or feoABC. Transport studies with intact cells showed that ZupT facilitates uptake of (55)Fe(2+) similarly to uptake of MntH or Feo. Other divalent cations were also taken up by ZupT, as shown using (57)Co(2+). Expression of zupT rendered E. coli cells hypersensitive to Co(2+) and sensitive to Mn(2+). ZupT did not appear to be metal regulated: expression of a Φ(zupT-lacZ) operon fusion indicated that zupT is expressed constitutively at a low level

The role of ants, birds and bats for ecosystem functions and yield in oil palm plantations

One of the world's most important and rapidly expanding crops, oil palm, is associated with low levels of biodiversity. Changes in predator communities might alter ecosystem services and subsequently sustainable management but these links have received little attention to date. Here, for the first time, we manipulated ant and flying vertebrate (birds and bats) access to oil palms in six smallholder plantations in Sumatra (Indonesia) and measured effects on arthropod communities, related ecosystem functions (herbivory, predation, decomposition and pollination) and crop yield. Arthropod predators increased in response to reductions in ant and bird access, but the overall effect of experimental manipulations on ecosystem functions was minimal. Similarly, effects on yield were not significant. We conclude that ecosystem functions and productivity in oil palm are, under current levels of low pest pressure and large pollinator populations, robust to large reductions of major predators