Cancer-Related Causes of Death among HIV-Infected Patients in France in 2010: Evolution since 2000

Objectives

The current study aimed at describing the distribution and characteristics of malignancy related deaths in human immunodeficiency virus (HIV) infected patients in 2010 and at comparing them to those obtained in 2000 and 2005.

Methods

Data were obtained from three national surveys conducted in France in 2010, 2005 and 2000. The underlying cause of death was documented using a standardized questionnaire fulfilled in French hospital wards involved in the management of HIV infection.

Results

Among the 728 deaths reported in 2010, 262 were cancer-related (36%). After a significant increase from 28% in 2000 to 33% in 2005 and 36% in 2010, cancers represent the leading cause of mortality in HIV infected patients. The proportion of deaths attributed to non-AIDS/non-hepatitis-related cancers significantly increased from 2000 to 2010 (11% of the deaths in 2000, 17% in 2005 and 22% in 2010, p<0.001), while those attributed to AIDS-defining cancers decreased during the same period (16% in 2000, 13% in 2005 and 9% in 2010, p = 0.024). Particularly, the proportion of respiratory cancers significantly increased from 5% in 2000 to 6% in 2005 and 11% in 2010 (p = 0.004). Lung cancer was the most common cancer-related cause of death in 2010 (instead of non-Hodgkin lymphoma so far) and represented the leading cause of death in people living with HIV overall.

Conclusions

Cancer prevention (especially smoking cessation), screening strategies and therapeutic management need to be optimized in HIV-infected patients in order to reduce mortality, particularly in the field of respiratory cancers.     

A test of biotic interactions among two alpine plant species in Australia

This study examines the extent to which interactions among two common alpine/subalpine plant species and their neighbours at the Bogong High Plains in southern Australia are characterized by competition or facilitation. The two target species were Celmisia pugioniformis (Asteraceae) and Carex breviculmis (Cyperaceae). Biotic interactions were examined using vegetation removal manipulations over three growing seasons at five sites across the altitudinal range of tall alpine herbfield communities. Observations recorded growth and mortality. Results for C. pugioniformis clearly indicated facilitation as a dominant process across all sites and seasons. Plants that had their neighbours removed tended to perform worse than plants that had their neighbours left intact. Growth observations for Ca. breviculmis were less clear, but again suggested facilitation. Mortality was distinctly higher among Ca. breviculmis individuals that had their neighbours removed relative to those with neighbours left intact. Results collectively suggest the removal of neighbours acts to reduce growth and increase mortality in C. pugioniformis and Ca. breviculmis throughout the altitudinal range of tall alpine herbfields at the Bogong High Plains. Facilitative and competitive interactions need to be recognized in efforts aimed at mitigating climate change‐associated impacts on the ecology of alpine plant communities. The extent to which biotic interactions may exacerbate or buffer abiotic change is difficult to predict, emphasizing the need for ecological monitoring.     

Constitutive expression of IL-22 in the human intervertebral disc and its reduction by exposure to pro-inflammatory cytokines in vitro

The importance of cytokines in disc degeneration is well recognized. Little is known about IL-22 expression in the human intervertebral disc. We investigated IL-22 immuno-localization in disc tissue, and molecular expression and production of IL-22 by annulus cells cultured in three-dimensional (3D) culture. We examined human disc tissue using immunohistochemistry and we cultured isolated annulus cells in 3D to analyze IL-22 expression and production, and its receptor, IL-22R, in conditioned media. Ingenuity pathway analysis (IPA) also was used to identify significant gene expression networks within the molecular data. IL-22 and IL-22R were immunolocalized in many cells in the human outer and inner annulus; fewer cells exhibited localization in the nucleus. Three-dimensional culture of annulus cells demonstrated production of IL-22 in conditioned media; exposure to IL-1ß or TNF-α significantly reduced IL-22 levels. Significant decreases also were identified in conditioned media assayed for IL-22R in TNF-α treated cells. IPA analysis showed that IL-22 ranked among the top canonical pathways. We found constitutive expression and production of IL-22 and IL-22R in the disc, which expands our understanding of the effect of pro-inflammatory cytokines on IL-22 expression and production. Three-dimensional cultured annulus cells exposed to IL-1ß or TNF produced significantly lower levels of IL-22 into their conditioned media compared to levels produced by control cells. Our findings have clinical relevance because of the elevated pro-inflammatory milieu within the degenerating human disc.     

Enzyme classification with peptide programs: a comparative study

Background  

Efficient and accurate prediction of protein function from sequence is one of the standing problems in Biology. The generalised use of sequence alignments for inferring function promotes the propagation of errors, and there are limits to its applicability. Several machine learning methods have been applied to predict protein function, but they lose much of the information encoded by protein sequences because they need to transform them to obtain data of fixed length.     

Penetrating Cations Enhance Uncoupling Activity of Anionic Protonophores in Mitochondria

Protonophorous uncouplers causing a partial decrease in mitochondrial membrane potential are promising candidates for therapeutic applications. Here we showed that hydrophobic penetrating cations specifically targeted to mitochondria in a membrane potential-driven fashion increased proton-translocating activity of the anionic uncouplers 2,4-dinitrophenol (DNP) and carbonylcyanide-p-trifluorophenylhydrazone (FCCP). In planar bilayer lipid membranes (BLM) separating two compartments with different pH values, DNP-mediated diffusion potential of H⁺ ions was enhanced in the presence of dodecyltriphenylphosphonium cation (C₁₂TPP). The mitochondria-targeted penetrating cations strongly increased DNP- and carbonylcyanide m-chlorophenylhydrazone (CCCP)-mediated steady-state current through BLM when a transmembrane electrical potential difference was applied. Carboxyfluorescein efflux from liposomes initiated by the plastoquinone-containing penetrating cation SkQ1 was inhibited by both DNP and FCCP. Formation of complexes between the cation and CCCP was observed spectophotometrically. In contrast to the less hydrophobic tetraphenylphosphonium cation (TPP), SkQ1 and C₁₂TPP promoted the uncoupling action of DNP and FCCP on isolated mitochondria. C₁₂TPP and FCCP exhibited a synergistic effect decreasing the membrane potential of mitochondria in yeast cells. The stimulating action of penetrating cations on the protonophore-mediated uncoupling is assumed to be useful for medical applications of low (non-toxic) concentrations of protonophores.     

Isolation and characterization of 23 polymorphic microsatellite markers for diversity and stock analysis in tiger shrimp (Penaeus monodon)

The tiger shrimp (Penaeus monodon) is an important marine crustacean in terms of biological diversity and aquaculture resource. The shrimp is widespread across the Indo‐Pacific region and shows apparent genetic differentiation among geographical populations. It is common practice to transport female brooders between different countries to seed the shrimp farms, posing potential problems of unwanted population admixture. We developed 23 polymorphic microsatellites for P. monodon (average H_E = 0.936) and these microsatellites were applicable for studying population differentiation, identifying valid stocks and tagging nonindigenous farmed shrimps.     

Tenascin in the human intervertebral disc: alterations with aging and disc degeneration

Our objective for this study was to determine the presence and distribution of tenascin in the human intervertebral disc. The tenascins are a family of extracellular matrix proteins with repeated structural domains homologous to epidermal growth factor, fibronectin type III and the fibrinogens. Little is known about the presence of this protein in the disc. Ten normal human discs donated from subjects newborn to 15 years old, 10 control discs from adult donors aged 24-41 years, and 11 surgical disc specimens from patients aged 26-76 years were examined for immunolocalization of tenascin. In young discs, tenascin was localized throughout the annulus; in the nucleus, localization was confined to pericellular matrix. In adult control and degenerating disc specimens, tenascin in the annulus was localized primarily in pericellular matrix regions encircling either single cells or clusters of disc cells; in rare instances localization was more diffuse in the intraterritorial matrix. In young, healthy disc, tenascin was abundant throughout the annulus. In contrast, degenerating discs in adults showed a localization restricted to the pericellular, and rarely, more restricted intraterritorial matrix. These observations indicate that changes in the amount and distribution of tenascin may have a role in disc aging and degeneration, possibly by modulating fibronectin-disc-cell interactions, and causing alterations in the shape of disc cells.     

Biosensor for the detection of bacteriophages based on a super-high-frequency resonator

Azospirillum lipoferum Sp59b microbial cells were immobilized on the surface of thin polystyrene films modified in plasma from a high-frequency discharge of argon (13.56 MHz). The optimal conditions for immobilization, under which cell activity was maintained with respect to specific bacteriophages, were established. It was shown that it is possible to record the interaction of immobilized microbial cells and bacteriophages with a microwave-based resonant system (5–8.5 GHz). It was found that the biosensor made it possible to distinguish the interaction of bacterial cells with specific bacteriophages from the control, in which such interaction was absent. With the obtained super-high-frequency sensor, it was possible to determine the content of ΦAl-Sp59b bacteriophages in a suspension containing ~106 phages/mL. The analysis time was about 10 min. The viability of microbial cells after immobilization was also determined with this sensor. The results obtained with the use of the sensor on the basis of a super-high-frequency resonator have shown that it is promising for the development of methods to determine viral particles and the viability of microbial cells.     

A method of acoustic analysis for detection of bacteriophage-infected microbial cells

The dependence of the changes of physical parameters of the suspension of Azospirillum brasilense Sp7 cells infected by FAb-Sp7 bacteriophage on their number and exposure time was studied using a biological sensor based on a piezoelectric resonator with a lateral electric field. The change in the value of the analytical signal was recorded at 1 minute from the beginning of the infection of the cells by bacteriophage. The selectivity of the action of the FAb-Sp7 bacteriophage was studied for Azospirillum brasilense (strains Cd, Sp107, Sp245, Jm6B2, Br14, KR77, S17, S27, SR55, and SR75), A. lipoferum (strains Sp59b, SR65, and RG20a), A. halopraeferans Au4, Nitrospirillum amazonense Am14, Niveispirillum irakense (strains KBC1 and KA3) bacteria, as well as for heterologous bacteria of the genera Escherichia coli (strains XL-1 and B-878), Pseudomonas putida (strains C-11 and BA-11), and Acinetobacter calcoaceticum A-122. The limit of the reliable determination of the concentration of microbial cells during bacteriophage infection process was found: ~10⁴ cells/mL. At the same time, the presence of heterologous cell cultures (E. coli XL-1 cells) did not complicate the detection. It was shown that the method of electroacoustical analysis of cell suspensions can be used for the detection of microbial cells of Azospirillum infected by the FAb-Sp7 bacteriophage. The results are promising for the development of methods for determining and controlling the number of soil microorganisms.