Allergen immunotherapy for allergic asthma: A systematic review and meta-analysis.

BACKGROUND: To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. METHODS: We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses. RESULTS: 98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of -1.11 (95% CI -1.66, -0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD -1.21 (95% CI -1.87, -0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95% CI -0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen-specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective. CONCLUSIONS: AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness.

Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer: Diagnostic and therapeutic potential.

Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC.

Prevention and control of childhood asthma and allergy in the EU from the public health point of view: Polish Presidency of the European Union.

The leading priority for the Polish Presidency of the Council of the European Union was to reduce health inequalities across European societies, and, within its framework, prevention and control of respiratory diseases in children. This very important paper contain proposal of international cooperation on the prevention, early detection and monitoring of asthma and allergic diseases in childhood which will be undertaken by the EU member countries as a result of EU conclusion developed during the Polish Presidency of the Council of the European Union. This will result in collaboration in the field of chronic diseases, particularly respiratory diseases, together with the activity of the network of national institutions and NGOs in this area. Paper also contains extensive analysis of the socio-economic, political, epidemiological, technological and medical factors affecting the prevention and control of childhood asthma and allergy presented during Experts presidential conference organized in Warsaw-Ossa 21-22 September 2011.

Abrupt burial imparts persistent changes to the bacterial diversity of turbidite-associated sediment profiles.

The emplacement of subaqueous gravity-driven sediment flows imposes a significant physical and geochemical impact on underlying sediment and microbial communities. Although previous studies have established lasting mineralogical and biological signatures of turbidite deposition, the response of bacteria and archaea within and beneath debris flows remains poorly constrained. Both bacterial cells associated with the underlying sediment and those attached to allochthonous material must respond to substantially altered environmental conditions and selective pressures. As a consequence, turbidites and underlying sediments provide an exceptional opportunity to examine (i) the microbial community response to rapid sedimentation and (ii) the preservation and identification of displaced micro-organisms. We collected Illumina MiSeq sequence libraries across turbidite boundaries at ~26 cm sediment depth in La Jolla Canyon off the coast of California, and at ~50 cm depth in meromictic Twin Lake, Hennepin County, MN. 16S rRNA gene signatures of relict and active bacterial populations exhibit persistent differences attributable to turbidite deposition. In particular, both the marine and lacustrine turbidite boundaries are sharply demarcated by the abundance and diversity of Chloroflexi, suggesting a characteristic sensitivity to sediment disturbance history or to differences in organic substrates across turbidite profiles. Variations in the abundance of putative dissimilatory sulfate-reducing Deltaproteobacteria across the buried La Jolla Canyon sediment-water interface reflect turbidite-induced changes to the geochemical environment. Species-level distinctions within the Deltaproteobacteria clearly conform to the sedimentological boundary, suggesting a continuing impact of genetic inheritance distinguishable from broader trends attributable to selective pressure. Abrupt, <1-cm scale changes in bacterial diversity across the Twin Lake turbidite contact are consistent with previous studies showing that relict DNA signatures attributable to sediment transport may be more easily preserved in low-energy, anoxic environments. This work raises the possibility that deep subsurface microbial communities may inherit variations in microbial diversity from sediment flow and deformation events.

Barite encrustation of benthic sulfur-oxidizing bacteria at a marine cold seep.

Crusts and chimneys composed of authigenic barite are found at methane seeps and hydrothermal vents that expel fluids rich in barium. Microbial processes have not previously been associated with barite precipitation in marine cold seep settings. Here, we report on the precipitation of barite on filaments of sulfide-oxidizing bacteria at a brine seep in the Gulf of Mexico. Barite-mineralized bacterial filaments in the interiors of authigenic barite crusts resemble filamentous sulfide-oxidizing bacteria of the genus Beggiatoa. Clone library and iTag amplicon sequencing of the 16S rRNA gene show that the barite crusts that host these filaments also preserve DNA of Candidatus Maribeggiatoa, as well as sulfate-reducing bacteria. Isotopic analyses show that the sulfur and oxygen isotope compositions of barite have lower δ(34)S and δ(18)O values than many other marine barite crusts, which is consistent with barite precipitation in an environment in which sulfide oxidation was occurring. Laboratory experiments employing isolates of sulfide-oxidizing bacteria from Gulf of Mexico seep sediments showed that under low sulfate conditions, such as those encountered in brine fluids, sulfate generated by sulfide-oxidizing bacteria fosters rapid barite precipitation localized on cell biomass, leading to the encrustation of bacteria in a manner reminiscent of our observations of barite-mineralized Beggiatoa in the Gulf of Mexico. The precipitation of barite directly on filaments of sulfide-oxidizing bacteria, and not on other benthic substrates, suggests that sulfide oxidation plays a role in barite formation at certain marine brine seeps where sulfide is oxidized to sulfate in contact with barium-rich fluids, either prior to, or during, the mixing of those fluids with sulfate-containing seawater in the vicinity of the sediment/water interface. As with many other geochemical interfaces that foster mineral precipitation, both biological and abiological processes likely contribute to the precipitation of barite at marine brine seeps such as the one studied here.

Fetal death during a negative contraction stress test.

This report describes a fetal death during a negative antepartum contraction stress test, without oxytocic stimulation, at 34 weeks' gestation in a woman with Class B diabetes mellitus.

Idiopathic scoliosis in three dimensions. A radiographic and morphometric analysis.

Eleven articulated scoliotic spines were examined radiographically and morphometrically. Measurement of the curve on anteroposterior radiographs of the specimens gave a mean Cobb angle of 70 degrees, though true anteroposterior radiographs of the deformity revealed a mean Cobb angle of 99 degrees (41% greater). Lateral radiographs gave the erroneous impression that there was a mean kyphosis of 41 degrees while true lateral projections revealed a mean apical lordosis of 14 degrees. Morphometric measurements confirmed the presence of a lordosis at bony level, the apical vertebral bodies being significantly taller anteriorly (P less than 0.02). There were significant correlations (P less than 0.01) between the true size of the lateral scoliosis, the amount of axial rotation and the size of the apical lordosis. This study illustrates the three-dimensional nature of the deformity in scoliosis and its property of changing in character and magnitude according to the plane of radiographic projection.

Some effects of urea on drug dissolution.

Solubilities and dissolution rates of salicylic acid have been determined in urea solutions at different pH values. Solubilities increased with pH and urea concentration; a solubilization mechanism was considered to be operating. The solubilization effect of urea was greatest on the non-ionzed moieties of the solute. Dissolution rates of salicylic acid increased with pH and urea concentration. The increase in dissolution rate paralleled increases in solubility. The role of solubilizing effect in the enhancement of dissolution rate by urea is discussed.

Some factors influencing dissolution from salicylic acid-urea solid dispersions.

Solid dispersion systems of salicylic acid-urea have been prepared using a fusion method. Two different methods of cooling the melt were employed, rapid cooling in liquid nitrogen and slow cooling in air. Differential scanning calorimetry and an X-ray diffraction technique were employed to investigate the nature of the fused mixture. Evidence was found of compound formation between the constituents. Dissolution rates of drug from non-disintegrating discs of solid dispersion systems were measured. Rapid cooling of the melt resulted in a much faster drug dissolution rate than from a corresponding mixture prepared by a slow cooling method. This phenomenon is explained by a difference in the sizes of drug particles produced under the different cooling conditions. Rapid cooling favoured the generation of many nucleation sites for the solid drug particles as the liquid was cooled, and hence many small particles were obtained. Conversely, slow cooling favoured the growth of the first few nuclei or solid drug particles, rather than the production of new nuclei, and hence large drug particles were obtained.

Rural hospitals' viability and strategic responses.

In 1989 the Catholic Health Association, in conjunction with the University of Iowa Center for Health Services Research, surveyed chief executive officers (CEOs) of rural hospitals regarding their hospital's viability and strategic behaviors and orientations. An extensive questionnaire was sent to the CEOs of all Catholic, all other religious not-for-profit, and all investor-owned rural hospitals, as well as to a 50 percent random sample of government and other not-for-profit rural hospitals. CEOs on average perceived that their hospital's viability relative to that of other rural hospitals was higher in 1989 than it had been in 1987. Ninety-four percent of hospitals whose CEOs perceived an increase in viability had been medium- or low-viability hospitals two years earlier. Thus, despite reports of deteriorating conditions for rural hospitals, rural hospital CEOs appeared to be relatively optimistic regarding their institution's viability. Changes in strategic direction accompanied these perceived increases in viability. The predominant strategic orientation adopted by rural hospitals in 1987 was that of the defender, but many hospitals that used this approach switched to the analyzer orientation by 1989. Significant shifts also occurred toward the reactor orientation from the analyzer and defender orientations. A greater percentage of hospitals with a perceived increase in viability between 1987 and 1989 altered their organizational role. The most common change for these hospitals was from limited care to basic care.

Horizontal gene transfer and the rock record: comparative genomics of phylogenetically distant bacteria that induce wrinkle structure formation in modern sediments.

Wrinkle structures are sedimentary features that are produced primarily through the trapping and binding of siliciclastic sediments by mat-forming micro-organisms. Wrinkle structures and related sedimentary structures in the rock record are commonly interpreted to represent the stabilizing influence of cyanobacteria on sediments because cyanobacteria are known to produce similar textures and structures in modern tidal flat settings. However, other extant bacteria such as filamentous representatives of the family Beggiatoaceae can also interact with sediments to produce sedimentary features that morphologically resemble many of those associated with cyanobacteria-dominated mats. While Beggiatoa spp. and cyanobacteria are metabolically and phylogenetically distant, genomic analyses show that the two groups share hundreds of homologous genes, likely as the result of horizontal gene transfer. The comparative genomics results described here suggest that some horizontally transferred genes may code for phenotypic traits such as filament formation, chemotaxis, and the production of extracellular polymeric substances that potentially underlie the similar biostabilizing influences of these organisms on sediments. We suggest that the ecological utility of certain basic life modes such as the construction of mats and biofilms, coupled with the lateral mobility of genes in the microbial world, introduces an element of uncertainty into the inference of specific phylogenetic origins from gross morphological features preserved in the ancient rock record.

Areawide suppression of European corn borer with Bt maize reaps savings to non-Bt maize growers.

Transgenic maize engineered to express insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) has become widely adopted in U.S. agriculture. In 2009, Bt maize was planted on more than 22.2 million hectares, constituting 63% of the U.S. crop. Using statistical analysis of per capita growth rate estimates, we found that areawide suppression of the primary pest Ostrinia nubilalis (European corn borer) is associated with Bt maize use. Cumulative benefits over 14 years are an estimated $3.2 billion for maize growers in Illinois, Minnesota, and Wisconsin, with more than $2.4 billion of this total accruing to non-Bt maize growers. Comparable estimates for Iowa and Nebraska are $3.6 billion in total, with $1.9 billion for non-Bt maize growers. These results affirm theoretical predictions of pest population suppression and highlight economic incentives for growers to maintain non-Bt maize refugia for sustainable insect resistance management.

Factors that predispose to premature rupture of the fetal membranes.

Causes of premature rupture of the fetal membranes were explored in a study of 25,820 pregnancies. Fourteen risk factors were analyzed using multivariate analysis. The following maternal factors had a positive association with premature ruptures: advanced maternal age, non-white race, multiparity, instrumentation of the cervix prior to pregnancy, cigarette smoking, incompetent cervix, low pregnancy weight gain, and recent coitus.