Rethinking the Poverty-disease Nexus: the Case of HIV/AIDS in South Africa

While it is well-established that poverty and disease are intimately connected, the nature of this connection and the role of poverty in disease causation remains contested in scientific and social studies of disease. Using the case of HIV/AIDS in South Africa and drawing on a theoretically grounded analysis, this paper reconceptualises disease and poverty as ontologically entangled. In the context of the South African HIV epidemic, this rethinking of the poverty-disease dynamic enables an account of how social forces such as poverty become embodied in the very substance of disease to produce ontologies of HIV/AIDS unique to South Africa

Perceived annoyance and asthmatic symptoms in relation to vehicle exhaust levels outside home: a cross-sectional study

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Exhaust emissions from vehicles is a well known problem with both epidemiological and experimental studies showing increasing adverse health effects with elevating levels. Many of the studies concerning vehicle exhausts and health are focused on health outcomes where the proportion attributed to exhaust is low, while there is less information on early and more frequent subjective indicators of adverse effects. Methods: The primary aim of this study was to study perceived annoyance in relation to vehicle exhaust concentrations using modelled levels of nitrogen dioxide outside the home as an indicator with high spatial resolution. Almost 2800 persons in a random sample from three Swedish cities (Umea, Uppsala and Gothenburg) responded to our questionnaire. Questions were asked to determine the degree of annoyance related to vehicle exhausts and also the prevalence of irritating and asthmatic symptoms. Exposure was described for each participants home address by meteorological dispersion models with a 50 meter resolution. Results: We found a significant increase of peoples ' self-assessed annoyance with rising levels of NO2. The odds of being very annoyed by vehicle exhausts increased by 14 % per 1 µg/m3 increas

RSpred, a set of Hidden Markov Models to detect and classify the RIFIN and STEVOR proteins of Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Many parasites use multicopy protein families to avoid their host's immune system through a strategy called antigenic variation. RIFIN and STEVOR proteins are variable surface antigens uniquely found in the malaria parasites <it>Plasmodium falciparum </it>and <it>P. reichenowi</it>. Although these two protein families are different, they have more similarity to each other than to any other proteins described to date. As a result, they have been grouped together in one Pfam domain. However, a recent study has described the sub-division of the RIFIN protein family into several functionally distinct groups. These sub-groups require phylogenetic analysis to sort out, which is not practical for large-scale projects, such as the sequencing of patient isolates and meta-genomic analysis.</p> <p>Results</p> <p>We have manually curated the <it>rif </it>and <it>stevor </it>gene repertoires of two <it>Plasmodium falciparum </it>genomes, isolates DD2 and HB3. We have identified 25% of mis-annotated and ~30 missing <it>rif </it>and <it>stevor </it>genes. Using these data sets, as well as sequences from the well curated reference genome (isolate 3D7) and field isolate data from Uniprot, we have developed a tool named RSpred. The tool, based on a set of hidden Markov models and an evaluation program, automatically identifies STEVOR and RIFIN sequences as well as the sub-groups: A-RIFIN, B-RIFIN, B1-RIFIN and B2-RIFIN. In addition to these groups, we distinguish a small subset of STEVOR proteins that we named STEVOR-like, as they either differ remarkably from typical STEVOR proteins or are too fragmented to reach a high enough score. When compared to Pfam and TIGRFAMs, RSpred proves to be a more robust and more sensitive method. We have applied RSpred to the proteomes of several <it>P. falciparum </it>strains, <it>P. reichenowi, P. vivax</it>, <it>P. knowlesi </it>and the rodent malaria species. All groups were found in the <it>P. falciparum </it>strains, and also in the <it>P. reichenowi </it>parasite, whereas none were predicted in the other species.</p> <p>Conclusions</p> <p>We have generated a tool for the sorting of RIFIN and STEVOR proteins, large antigenic variant protein groups, into homogeneous sub-families. Assigning functions to such protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. RSpred removes the need for complicated and time consuming phylogenetic analysis methods. It will benefit both research groups sequencing whole genomes as well as others working with field isolates. RSpred is freely accessible via <url>http://www.ifm.liu.se/bioinfo/</url>.</p

Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE ε3/ε3 Subjects

Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E ε4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 ε3/ε3 carriers; 28 ε4 carriers) aged 49–79 yr. Leukocyte telomere length correlated inversely with left (rs = −0.465; p = 0.011), right (rs = −0.414; p = 0.025), and total hippocampus volume (rs = −0.519; p = 0.004) among APOE ε3/ε3 carriers, but not among ε4 carriers. However, the ε4 carriers fit with the general correlation pattern exhibited by the ε3/ε3 carriers, as ε4 carriers on average had longer telomeres and smaller hippocampi compared with ε3/ε3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain

Transfer of immunoglobulins through the mammary endothelium and epithelium and in the local lymph node of cows during the initial response after intramammary challenge with E. coli endotoxin

<p>Abstract</p> <p>Background</p> <p>The first hours after antigen stimulation, interactions occur influencing the outcome of the immunological reaction. Immunoglobulins originate in blood and/or are locally synthesized. The transfer of Ig isotypes (Igs) in the udder has been studied previously but without the possibility to distinguish between the endothelium and the epithelium. The purpose of this study was to map the Ig transfer through each barrier, separately, and Ig transfer in the local lymph nodes of the bovine udder during the initial innate immune response.</p> <p>Methods</p> <p>The content of IgG1, IgG2, IgM, IgA and albumin (BSA) was examined in peripheral/afferent mammary lymph and lymph leaving the supramammary lymph nodes, and in blood and milk before (0 h) and during 4 hours after intramammary challenge with <it>Esherichia coli </it>endotoxin in 5 cows.</p> <p>Results</p> <p>Igs increased most rapidly in afferent lymph resulting in higher concentrations than in efferent lymph at postinfusion hour (PIH) 2, contrary to before challenge. Ig concentrations in milk were lower than in lymph; except for IgA at 0 h; and they increased more slowly. <it>Afferent lymph:serum </it>and <it>efferent lymph:serum </it>concentration ratios (CR) of Igs were similar to those of BSA but slightly lower. <it>Milk:afferent lymph </it>(M:A) CRs of each Ig, except for IgG2, showed strikingly different pattern than those of BSA. The M:A CR of IgG1, IgM and IgA were higher than that of BSA before challenge and the CR of IgA and IgG1 remained higher also thereafter. At PIH 2 there was a drop in Ig CRs, except for IgG2, in contrast to the BSA CR which gradually increased. The M:A CR of IgM and Ig A <it>decreased </it>from 0 h to PIH 4, in spite of increasing permeability.</p> <p>Conclusion</p> <p>The transfer of Igs through the <it>endothelium </it>appeared to be merely a result of diffusion although their large molecular size may hamper the diffusion. The transfer through the <it>epithelium </it>and the Ig concentrations in milk seemed more influenced by selective mechanisms and local sources, respectively. Our observations indicate a selective mechanism in the transfer of IgG1 through the epithelium also in lactating glands, not previously shown; a local synthesis of IgA and possibly of IgM, released primarily into milk, not into tissue fluid; that IgG2 transfer through both barriers is a result of passive diffusion only and that the content of efferent lymph is strongly influenced by IgG1, IgM and IgA in the mammary tissue, brought to the lymph node by afferent lymph.</p

Proximal major limb amputations – a retrospective analysis of 45 oncological cases

<p>Abstract</p> <p>Background</p> <p>Proximal major limb amputations due to malignant tumors have become rare but are still a valuable treatment option in palliation and in some cases can even cure. The aim of this retrospective study was to analyse outcome in those patients, including the postoperative course, survival, pain, quality of life, and prosthesis usage.</p> <p>Methods</p> <p>Data of 45 consecutive patients was acquired from patient's charts and contact to patients, and general practitioners. Patients with interscapulothoracic amputation (n = 14), shoulder disarticulation (n = 13), hemipelvectomy (n = 3) or hip disarticulation (n = 15) were included.</p> <p>Results</p> <p>The rate of proximal major limb amputations in patients treated for sarcoma was 2.3% (37 out of 1597). Survival for all patients was 42.9% after one year and 12.7% after five years. Survival was significantly better in patients with complete tumor resections. Postoperative chemotherapy and radiation did not prolong survival. Eighteen percent of the patients with malignant disease developed local recurrence. In 44%, postoperative complications were observed. Different modalities of postoperative pain management and the site of the amputation had no significant influence on long-term pain assessment and quality of life. Eighty-seven percent suffered from phantom pain, 15.6% considered their quality of life worse than before the operation. Thirty-two percent of the patients who received a prosthesis used it regularly.</p> <p>Conclusion</p> <p>Proximal major limb amputations severely interfere with patients' body function and are the last, albeit valuable, option within the treatment concept of extremity malignancies or severe infections. Besides short survival, high complication rates, and postoperative pain, patients' quality of life can be improved for the time they have remaining.</p

Physiologically based pharmacokinetic modeling of arterial – antecubital vein concentration difference

BACKGROUND: Modeling of pharmacokinetic parameters and pharmacodynamic actions requires knowledge of the arterial blood concentration. In most cases, experimental measurements are only available for a peripheral vein (usually antecubital) whose concentration may differ significantly from both arterial and central vein concentration. METHODS: A physiologically based pharmacokinetic (PBPK) model for the tissues drained by the antecubital vein (referred to as "arm") is developed. It is assumed that the "arm" is composed of tissues with identical properties (partition coefficient, blood flow/gm) as the whole body tissues plus a new "tissue" representing skin arteriovenous shunts. The antecubital vein concentration depends on the following parameters: the fraction of "arm" blood flow contributed by muscle, skin, adipose, connective tissue and arteriovenous shunts, and the flow per gram of the arteriovenous shunt. The value of these parameters was investigated using simultaneous experimental measurements of arterial and antecubital concentrations for eight solutes: ethanol, thiopental, (99)Tc(m)-diethylene triamine pentaacetate (DTPA), ketamine, D(2)O, acetone, methylene chloride and toluene. A new procedure is described that can be used to determine the arterial concentration for an arbitrary solute by deconvolution of the antecubital concentration. These procedures are implemented in PKQuest, a general PBPK program that is freely distributed . RESULTS: One set of "standard arm" parameters provides an adequate description of the arterial/antecubital vein concentration for ethanol, DTPA, thiopental and ketamine. A significantly different set of "arm" parameters was required to describe the data for D(2)O, acetone, methylene chloride and toluene – probably because the "arm" is in a different physiological state. CONCLUSIONS: Using the set of "standard arm" parameters, the antecubital vein concentration can be used to determine the whole body PBPK model parameters for an arbitrary solute without any additional adjustable parameters. Also, the antecubital vein concentration can be used to estimate the arterial concentration for an arbitrary input for solutes for which no arterial concentration data is available

The Critical Richardson Number and Limits of Applicability of Local Similarity Theory in the Stable Boundary Layer

Measurements of atmospheric turbulence made over the Arctic pack ice during the Surface Heat Budget of the Arctic Ocean experiment (SHEBA) are used to determine the limits of applicability of Monin-Obukhov similarity theory (in the local scaling formulation) in the stable atmospheric boundary layer. Based on the spectral analysis of wind velocity and air temperature fluctuations, it is shown that, when both of the gradient Richardson number, Ri, and the flux Richardson number, Rf, exceed a 'critical value' of about 0.20 - 0.25, the inertial subrange associated with the Richardson-Kolmogorov cascade dies out and vertical turbulent fluxes become small. Some small-scale turbulence survives even in this supercritical regime, but this is non-Kolmogorov turbulence, and it decays rapidly with further increasing stability. Similarity theory is based on the turbulent fluxes in the high-frequency part of the spectra that are associated with energy-containing/flux-carrying eddies. Spectral densities in this high-frequency band diminish as the Richardson-Kolmogorov energy cascade weakens; therefore, the applicability of local Monin-Obukhov similarity theory in stable conditions is limited by the inequalities Ri < Ri_cr and Rf < Rf_cr. However, it is found that Rf_cr = 0.20 - 0.25 is a primary threshold for applicability. Applying this prerequisite shows that the data follow classical Monin-Obukhov local z-less predictions after the irrelevant cases (turbulence without the Richardson-Kolmogorov cascade) have been filtered out.Comment: Boundary-Layer Meteorology (Manuscript submitted: 16 February 2012; Accepted: 10 September 2012

Overexpression of endothelial nitric oxide synthase suppresses features of allergic asthma in mice

BACKGROUND: Asthma is associated with airway hyperresponsiveness and enhanced T-cell number/activity on one hand and increased levels of exhaled nitric oxide (NO) with expression of inducible NO synthase (iNOS) on the other hand. These findings are in paradox, as NO also relaxes airway smooth muscle and has immunosuppressive properties. The exact role of the endothelial NOS (eNOS) isoform in asthma is still unknown. We hypothezised that a delicate regulation in the production of NO and its bioactive forms by eNOS might be the key to the pathogenesis of asthma. METHODS: The contribution of eNOS on the development of asthmatic features was examined. We used transgenic mice that overexpress eNOS and measured characteristic features of allergic asthma after sensitisation and challenge of these mice with the allergen ovalbumin. RESULTS: eNOS overexpression resulted in both increased eNOS activity and NO production in the lungs. Isolated thoracic lymph nodes cells from eNOS overexpressing mice that have been sensitized and challenged with ovalbumin produced significantly less of the cytokines IFN-γ, IL-5 and IL-10. No difference in serum IgE levels could be found. Further, there was a 50% reduction in the number of lymphocytes and eosinophils in the lung lavage fluid of these animals. Finally, airway hyperresponsiveness to methacholine was abolished in eNOS overexpressing mice. CONCLUSION: These findings demonstrate that eNOS overexpression attenuates both airway inflammation and airway hyperresponsiveness in a model of allergic asthma. We suggest that a delicate balance in the production of bioactive forms of NO derived from eNOS might be essential in the pathophysiology of asthma

Recruitment of the Major Vault Protein by InlK: A Listeria monocytogenes Strategy to Avoid Autophagy

L. monocytogenes is a facultative intracellular bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The infectious process at the cellular level has been extensively studied and many virulence factors have been identified. Yet, the role of InlK, a member of the internalin family specific to L. monocytogenes, remains unknown. Here, we first show using deletion analysis and in vivo infection, that InlK is a bona fide virulence factor, poorly expressed in vitro and well expressed in vivo, and that it is anchored to the bacterial surface by sortase A. We then demonstrate by a yeast two hybrid screen using InlK as a bait, validated by pulldown experiments and immunofluorescence analysis that intracytosolic bacteria via an interaction with the protein InlK interact with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoproteic particules named vaults. Although vaults have been implicated in several cellular processes, their role has remained elusive. Our analysis demonstrates that MVP recruitment disguises intracytosolic bacteria from autophagic recognition, leading to an increased survival rate of InlK over-expressing bacteria compared to InlK− bacteria. Together these results reveal that MVP is hijacked by L. monocytogenes in order to counteract the autophagy process, a finding that could have major implications in deciphering the cellular role of vault particles