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To investigate the incidence, risk factors, and outcomes of barotrauma (pneumomediastinum and subcutaneous emphysema) in mechanically ventilated COVID-19 patients. To describe the chest radiography patterns of barotrauma and understand the development in relation to mechanical ventilation and patient mortality.We performed a retrospective study of 363 patients with COVID-19 from March 1 to April 8, 2020. Primary outcomes were pneumomediastinum or subcutaneous emphysema with or without pneumothorax, pneumoperitoneum, or pneumoretroperitoneum. The secondary outcomes were length of intubation and death. In patients with pneumomediastinum and/or subcutaneous emphysema, we conducted an imaging review to determine the timeline of barotrauma development.Forty three out of 363 (12%) patients developed barotrauma radiographically. The median time to development of either pneumomediastinum or subcutaneous emphysema was 2 days (IQR 1.0-4.5) after intubation and the median time to pneumothorax was 7 days (IQR 2.0-10.0). The overall incidence of pneumothorax was 28/363 (8%) with an incidence of 17/43 (40%) in the barotrauma cohort and 11/320 (3%) in those without barotrauma (p ≤ 0.001). In total, 257/363 (71%) patients died with an increase in mortality in those with barotrauma 33/43 (77%) vs. 224/320 (70%). When adjusting for covariates, barotrauma was associated with increased odds of death (OR 2.99, 95% CI 1.25-7.17).Barotrauma is a frequent complication of mechanically ventilated COVID-19 patients. In comparison to intubated COVID-19 patients without barotrauma, there is a higher rate of pneumothorax and an increased risk of death.

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials. The need for further validation in comparison with field exposure is clearly mandated. On this basis, the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments. Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) airflow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non-contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed.

Since the outbreak of the ongoing pandemic of the novel coronavirus disease (COVID-19) in Wuhan, China, from December 2019, we have learned that multiple organs can be affected with the potential for various complications. Although myalgia is a frequent symptom in COVID- 19 patients, no imaging findings of rhabdomyolysis have been featured in the literature. We report a case of presumed rhabdomyolysis in a 38-year-old male with COVID-19 based on the clinical presentation, laboratory results and radiological findings. By discussing the diagnostic rationale and reviewing the relevant literature we hope to advance the existing understanding of this disease and its effects on the musculoskeletal system.

Allergic respiratory disease represents a significant and expanding health problem worldwide. Allergic symptoms, such as asthma and hay fever, cause sleep impairment and reduce school and work performance. The cost to society is substantial. Allergen avoidance and pharmacotherapy cannot control the disease. Only allergy immunotherapy has disease-modifying potential and should be included in optimal treatment strategies. Allergy immunotherapy was first administered as subcutaneous injections and has been practiced for the past 100 years or so. Recently, tablet-based sublingual allergy immunotherapy (SLIT) was introduced with comprehensive clinical documentation. SLIT tablets represent a more patient-friendly concept because they can be used for self-treatment at home.

[1] This paper presents a tool for calculating the Palmer Drought Severity Index (PDSI) and associated drought indices. The PDSI is a widely used drought index, yet the complexity and lack of transparency associated with the calculation of the PDSI makes it difficult for a researcher to independently calculate the index. Researchers are often forced to use PDSI values supplied by the National Climatic Data Center (NCDC) of the National Oceanic and Atmospheric Administration (NOAA) or some other third party. The MATLAB tool presented here is easy to use, thoroughly documented, and transparent. The tool was developed by checking an independently developed code against NCDC's FORTRAN code. Discrepancies between the MATLAB tool and the NCDC code are documented. Researchers using the tool will be able to easily calculate the Palmer drought indices for data inputs of any length and at any spatial scale.

Background Treatment with SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is effective for HDM respiratory allergic disease, but data on long-term effects are lacking. Objective Post hoc analyses were conducted to determine the long-term effect of SQ HDM SLIT-tablet on nasal, ocular, and cough symptoms 1 year after discontinuation of treatment. Methods Study participants underwent environmental exposure chamber (EEC) challenges at baseline and week 24 in a randomized, placebo-controlled, double-blind trial (NCT01644617) during which participants received daily 12 SQ-HDM, 6 SQ-HDM, or placebo for 24 weeks. Asthma had to be stable, well controlled, and nonsevere. The mean total asthma symptom score (TASS; sum of 3 symptoms: cough, wheeze, and dyspnea) during baseline and week 24 EEC challenge was analyzed in all participants who completed the trial (n = 106). Approximately 1 year after trial completion, another EEC challenge was conducted in a subset of participants (n = 51). Total nasal symptom score (sum of 4 symptoms), total ocular symptom score (sum of 2 symptoms), and cough were assessed. Results Compared with baseline and end-of-treatment values, sustained improvement of all symptoms assessed at the 1-year follow-up EEC challenge was evident in participants treated with 12 SQ-HDM. Results with 6 SQ-HDM were less notable. After 24 weeks of 12 SQ-HDM, TASS during EEC challenge was improved 65% vs baseline; at 1-year follow-up, cough was improved 57% vs baseline. Conclusion Persistent improvement of nasal and ocular symptoms was observed up to 1 year after completing 24 weeks of 12 SQ-HDM treatment. Beneficial effects on cough were also observed. Trial Registration clinicaltrials.gov Identifier NCT01644617.

Background: Allergen-specific immunotherapy (SIT) leads to reduced symptoms upon allergen exposure through as yet unresolved mechanisms. Desensitization of basophils to specific allergens during the updosing phase of injection immunotherapy may contribute to the clinical effect of SIT. Here we report a protocol for efficient in vitro allergen-mediated desensitization of basophils in whole blood and the effect of desensitization on the expression of basophil activation markers (CD203c and CD63) as well as histamine release in response to allergen challenge. Methods: Whole blood from grass pollen-allergic subjects was incubated with Phleum pratense extract by stepwise increase of the allergen concentration in the culture from well below to well above the allergen threshold concentration for activation of basophils. Desensitization was determined by measuring the expression of the basophil activation markers CD63 and CD203c by FACS following challenge with high allergen concentrations. Results: The basophil desensitization protocol reported here affected both the expression of the cell-surface markers and the levels of histamine release. Following the stepwise desensitization procedure the whole-blood basophils were not activated when challenged with more than 10-fold increased allergen concentration. Conclusion: We have established a protocol for basophil desensitization. By mimicking the updosing phase of immunotherapy we raised the allergen threshold for basophil activation and obtained efficient desensitization for all donors. We showed that conditions leading to desensitization affect histamine release and expression of different basophil markers alike.

Background: The incidence of allergic diseases is increasing in industrialized countries and the immunological mechanisms leading to tolerance or allergy are poorly understood. Cytokines with suppressive abilities and CD4+CD25+ regulatory T cells have been suggested to play a central role in allergen-specific responses. The aim was to determine whether major grass allergens induce production of suppressive cytokines in allergic and healthy subjects and to examine the inhibitory effect of these cytokines on allergic responses. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy and grass-allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5. The effects of endogenous IL-10 and/or TGF-β on proliferation and cytokine production were determined by use of blocking antibodies. In addition, the number of CD4+CD25+ T cells and their expression of chemokine receptors were investigated by flow cytometry. Results: Phl p 1 and Phl p 5 induced IL-10 production, which down-regulated proliferation and cytokine production, in PBMC cultures from atopic but not from non-atopic donors. Comparable frequencies of CD4+CD25+ T cells were present in PBMCs in the two groups, but fewer cells from atopic donors were CD4+CD25+CCR4+ and more cells were CD4+CD25+CLA+ compared to healthy donors. Conclusion:Allergen-specific responses of grass allergic patients but not in non-atopic subjects are influenced by regulatory cytokines produced in response to the important allergens. Differences in CD4+CD25+ T cell expression of chemokine receptors in allergic compared to non-atopic donors could suggest that the homing of CD4+CD25+ T cells is important for the regulation of allergen-specific responses.

Water scarcity is intensified by drought, a phenomenon that impacts many sectors of society and affects virtually all climate zones. The Palmer drought indices are widely used by scientists and policy makers to understand drought and model its components. Despite the spatial heterogeneity and variability in variables required by the Palmer model, regional index values are most commonly used for real-time drought assessment. Local stakeholders charged with developing flexible and tailored water management policies have articulated the need for drought indices calculated at finer spatial resolutions than a regional scale. We use the Pacific Northwest United States (U.S.) as a study area to demonstrate the differences between drought indices calculated for U.S. climate divisions with those calculated at a 0.5° by 0.5° latitude/longitude resolution. Our results indicate that regional values of the two cumulative Palmer drought indices do not represent finer-resolution values well. For half of the study area, the pictures of drought (as determined by regional and finer-resolution values) are drastically different more than 30% of the time. Thus, quite often water managers do not have a clear understanding of the relative severity of drought in their area, which can have serious implications for drought mitigation and adaptation.

Summary Background Human basophils and mast cells express the low-affinity immunoglobulin (Ig)G receptor FcγRIIB. It has previously been shown in artificial model systems that cross-linking of the high-affinity IgE receptor FcɛRI and FcγRIIB leads to inhibition of FcɛRI signalling. Objective The aim of the present study was to investigate whether cross-linking of FcɛRI and FcγRIIB contributes to IgG-mediated inhibition of histamine release in human basophils in a system using the sera from specific immunotherapy (SIT) patients and the major allergen from birch pollen, Bet v 1. As IgG4 furthermore has been proposed to have special blocking properties, we investigated the significance of IgG subclass specificity for this inhibition. Methods Binding of recombinant Bet v 1–IgG complexes to FcγRII and IgG-binding activities in the sera from 25 birch pollen-allergic patients treated with SIT were measured using 125I-rBet v 1. Inhibition of basophil histamine release was assessed by incubating washed leucocytes with complexes of rBet v 1–IgG with or without blocking of FcγRII. Results We observed low binding of rBet v 1–IgG complexes to FcγRII, which was negatively correlated with the relative IgG4-binding activities. Blocking of FcγRII did not reverse the SIT–IgG-induced inhibition of basophil histamine release. However, IgG-binding activities correlated significantly with the ability of the SIT sera to inhibit basophil histamine release. Conclusion We suggest that at least in birch pollen SIT, the contribution of FcγRIIB-mediated inhibitory signalling to SIT–IgG-induced inhibition of human basophil histamine release is of minor importance. The main contributor to the inhibitory effect of SIT-induced IgG seems to be blocking of the allergen–IgE interaction.

In Westeuropa dominieren stumpfe Verletzungen des Thorax, penetrierende Verletzungen sind Raritaten. Entsprechend wenig Routine besteht in der Versorgung Letzterer, sie orientiert sich an den Erfahrungen aus den USA und Sudafrika. Wahrend penetrierende Verletzungen haufig operativ versorgt werden mussen, konnen die meisten stumpfen Traumen konservativ bzw. mit Thoraxdranage und maschineller Beatmung suffizient behandelt werden. Bei insgesamt niedriger Frequenz ist es umso wichtiger, die Falle zu erkennen, bei denen eine Thorakotomie erforderlich ist. Neben der akuten Versorgung spielt insbesondere die konsequente Therapie des sich haufig entwickelnden ARDS eine wichtige Rolle. Therapiepfeiler sind die Lungen schonende maschinelle Beatmung, die nicht standardisiert, sondern individuell angepasst erfolgen muss, die Flussigkeitsrestriktion sowie die Lagerungstherapie. Trotz vieler Versuche spielen adjuvante medikamentose Therapien und die Lungenersatzverfahren nur eine untergeordnete Rolle.

Weight per metre and strand circumference were measured, using sensitive methods, on 177 mm round strands, with particular attention being paid to phase transformation and thermal shrinkage in the vicinity of the peritectic. The following results were achieved for a broad range of steel grades. With constant mould dimensions, the weight per metre of round continuously cast strand increases as casting speed rises. Soft steels, such as grade S35 containing 0·10%C, have a low weight per metre, whereas harder grades, such as C60 with 0·60%C, have the highest weight per metre. Low alloyed steels and oilfield tubular grades occupy rankings between these extremes. Martensitic and more highly resulphurised round billets have a conspicuously low weight per metre. The following definitive influencing factors on weight per metre became apparent: expansion of the mould tube under exposure to heat; shrinkage as a result of δ - γ transformation; creep processes under exposure to ferrostatic pressure; density of...

The MIDAS method (Mannesmann inclusion detection by analysing surfboards) was established in 1987 and enabled steelmakers to detect less frequent macroscopic inclusion particles in large volumes of steel. The basic idea of MIDAS is the flat cross-rolling of a strand sample perpendicular to the casting direction. Improvements in secondary metallurgy and casting technology have been achieved, since it became possible to define macrocleanness in exact numbers. In this paper, MIDAS results are presented for various strand sections: billets, blooms, jumbo blooms, round strands, conventional slabs and thin slabs. The variation of cleanness during sequence casting, at the front portion and end portion of heats, at ladle change and during steady state casting is investigated. The effect of teeming disturbances and accidental casting events on macrocleanness is studied. Selection of clean material can be optimised by adjusting the cutting length and downgrading critical casting portions. Detected inclusion...

Background: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America. Methods: Thirty-five patients with severe rhinoconjunctivitis (hay fever) to birch pollen were allocated to double-blinded clustered IT with a depot birch pollen extract (Betula verrucosa) or placebo injections. Seven patients in each group had concomitant self-reported seasonal asthma. Treatment was conducted as a clustered regimen and was performed in a specialist unit. Symptom scores from nose, eyes, and lungs, and use of oral and topical antihistamines, beta-2-agonists, and oral corticosteroids were recorded daily during the season of 2000. Sensitivity to allergen provocation in skin, conjunctiva, and nasal mucosa was measured before and after 10 months of treatment. Post-seasonal assessment of symptom severity was performed using a simple questionnaire. Results: IT reduced the symptom score for both rhinoconjunctivitis and asthma (P-values

CXC chemokine receptor 3 (CXCR3), which is known to be expressed predominately on memory and activated T lymphocytes, is a receptor for both interferon γ (IFN-γ)–inducible protein 10 (γIP-10) and monokine induced by IFN-γ (Mig). We report the novel finding that CXCR3 is also expressed on CD34+ hematopoietic progenitors from human cord blood stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) but not on freshly isolated CD34+ progenitors. Freshly isolated CD34+progenitors expressed low levels of CXCR3 messenger RNA, but this expression was highly up-regulated by GM-CSF, as indicated by a real-time quantitative reverse transcriptase–polymerase chain reaction technique. γIP-10 and Mig induced chemotaxis of GM-CSF–stimulated CD34+ progenitors by means of CXCR3, since an anti-CXCR3 monoclonal antibody (mAb) was found to block γIP-10–induced and Mig-induced CD34+ progenitor chemotaxis. These chemotactic attracted CD34+ progenitors are colony-forming units—granulocyte-macrophage. γIP-10 and Mig also induced GM-CSF–stimulated CD34+ progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 mAb blocked these functions of γIP-10 and Mig but not of chemokine stromal cell–derived factor 1α. γIP-10–induced and Mig-induced up-regulation of integrins (CD49a and CD49b) was found to play a crucial role in adhesion of GM-CSF–stimulated CD34+progenitors. Moreover, γIP-10 and Mig stimulated CXCR3 redistribution and cellular polarization in GM-CSF–stimulated CD34+progenitors. These results indicate that CXCR3–γIP-10 and CXCR3–Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment for the physiologic and pathophysiologic events of differentiation of CD34+ hematopoietic progenitors into lymphoid and myeloid stem cells, subsequently immune and inflammatory cells. These processes include transmigration, relocation, differentiation, and maturation of CD34+ hematopoietic progenitors.

We report that interleukin (IL)-4 and IL-10 can significantly up- or down-regulate CXC chemokine receptor 4 (CXCR4) expression on CD4+ T lymphocytes, respectively. Stromal cell-derived factor-1alpha (SDF-1alpha)-induced CD4+ T-lymphocyte chemotaxis was also correspondingly regulated by IL-4 and IL-10. IL-4 and IL-10 up- or down-regulated CXCR4 mRNA expression in CD4+ T lymphocytes, respectively, as detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Scatchard analysis revealed a type of CXCR4 with affinity (Kd approximately 6.3 nM), and approximately 70,000 SDF-1alpha-binding sites per cell, among freshly isolated CD4+ T lymphocytes, and two types of CXCR4 with different affinities (Kd1 approximately 4.4 nM and Kd2 approximately 14.6 nM), and a total of approximately 130,000 SDF-1alpha-binding sites per cell, among IL-4-stimulated CD4+ T lymphocytes. The regulation of CXCR4 expression in CD4+ T lymphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of protein kinase (staurosporine) or by a selective inhibitor of cAMP- and cGMP-dependent protein kinase (H-8), indicating that these cytokines regulate CXCR4 on CD4+ T lymphocytes via both cAMP and cGMP signalling pathways. The fact that cyclosporin A or ionomycin were able to independently change the CXCR4 expression and block the effects of IL-4 and IL-10 on CXCR4 expression implied that the capacity of IL-4 and IL-10 to regulate CXCR4 on CD4+ T lymphocytes is not linked to calcium-mobilization stimulation. These results indicate that the effects of IL-4 and IL-10 on the CXCR4-SDF-1 receptor-ligand pair may be of particular importance in the cytokine/chemokine environment concerning the inflammatory processes and in the progression of human immunodeficiency virus (HIV) infection.

We report that NF-AT1 and NF-AT4 are expressed cytoplasmically in resting eosinophils, whereas NF-AT2 and NF-AT3 have not been seen. Likewise, NF-AT1 mRNA and NF-AT4 mRNA have been detected in resting eosinophils, and their levels can be significantly up-regulated by the Th2-associated cytokines IL-4 and IL-5. There is no detectable NF-AT protein expression in the nuclei of resting eosinophils. However NF-ATs appear in the nuclei of IL-4-, IL-5-, or ionomycin-stimulated eosinophils. Only NF-AT1 and NF-AT4, but not NF-AT2 and NF-AT3, have translocated into the nuclei in IL-4- or IL-5-stimulated eosinophils. These findings delineate a novel pathway in the cytokine network in which Th2 lymphocytes “control” eosinophils via the release of IL-4 and IL-5, and activation of NF-AT in eosinophils. The findings also suggest that a later feedback “talking” may exist between eosinophils and Th2 lymphocytes.

Background The level of histamine in nasal lavage fluid has been used as an index of mast cell/basophil activation in a number of studies. Obviously, such an index can only be valid if changes in the secretory activity of nasal glands do not affect the level of histamine in lavage fluid (i.e. hypersecretion, without a simultaneous activation of mast cells/basophils in the nasal mucosa, must not increase the level of histamine). Objectives To asses the effect of nasal hypersecretion on histamine levels in lavage fluid. Methods Nasal challenges were performed with methacholine and allergen in grass pollen-allergic patients and non-allergic controls. Nasal lavage fluid was collected before and repeatedly for nine hours after nasal challenge, and the level of histamine was compared with that of a specific mast cell-derived enzyme, tryptase. In addition, the effect of methacholine on basophils was examined in vitro. Results Allergen challenge of allergic patients produced sneezing and a significant increase in histamine and tryptase levels, whereas challenge of non-allergic subjects produced no such response. Interestingly, challenge with methacholine also induced a significant increase in histamine levels. This increase was seen in both allergic and non-allergic subjects and it was not associated with any sneezing or increase in tryptase levels, indicating that mast cells were not activated. Furthermore, stimulation of basophils with methacholine did not induce any histamine release in vitro. Conclusions Apparently, there exists a pool of histamine in the human nose that can be transferred to lavage fluid during glandular hypersecretion. The source of this histamine is yet to be identified. As the level of histamine seems to be affected by the secretory activity of nasal glands, we question the use of this single mediator as an index of mast cell/basophil activation in nasal lavage studies.

A program was created for calculating the orientation distribution function of textures for all crystal systems. The method corresponds to a superposition of pole figures. This program, which follows the WIMV procedure, is based on a direction-dependent representation in the reciprocal space. The advantage over representation with Eulerian angles is that an axial transformation is not necessary in the oblique crystal systems. Fibre textures appear in the diagrammes as one-dimensional stripes. Different components of a fibre texture can be clearly depicted in a stereographic projection. The occurrence of twins and oriented intergrowths can be determined. Results of texture determinations on copper from a plumbing system and on a polycrystalline gypsum preparation are given below.

Parts I and II investigated twins that form when a more favourable energetic transition structure initially occurs which then, at a certain growth stage (presumably in the nm-range), transform into a more symmetric structural arrangement. These transition structures, which could explain the transformation between the twin individuals, were found using lattice energy calculations on organic substances such as pentaerythrite, 1,2,4,5-tetrabromobenzene, 3,5-dimethylbenzoic acid, and maleic acid. The formation of a more favourable energetic but symmetrically lower transition structure is more likely. when lattice pseudosymmetries are present. Experimentally proving these transition structures is extremely difficult because of their low volume. It has nevertheless been possible to detect such a transition structure — around which crystal growth begins — in many metallic vapour-deposit layers. Crystal growth begins around a core and then continues as a three-dimensional periodically ordered cubic face-centered structure, at which point twins form. In Part III, the attempt is made to confirm these processes with energy calculations. In Teil I und II wurden Zwillinge untersucht, die dadurch entstehen, das primar eine energetisch gunstigere Zwischenstruktur entsteht, die von einem bestimmten Wachstumsstadium an (vermutlich im nm-Bereich) in eine symmetrischere Strukturanordnung ubergeht. Diese Zwischenstrukturen, die den Ubergang zwischen den Zwillingsindividuen erklaren konnen, wurden mit Hilfe von Gitterenergieberechnungen an organischen Substanzen wie Pentaerythrit, 1,2,4,5-Tetrabrombenzol, 3,5-Dimethylbenzoeesaure und Maleinsaure gefunden. Die Bildung einer energetisch gunstigeren aber symmetrisch niedrigeren Zwischenstruktur wird durch Pseudosymmetrien des Gitters begunstigt. Der experimentelle Nachweis dieser Zwischenstrukturen gestaltet sich aufgrund ihres geringen Volumens auserst schwierig. In vielen metallischen Aufdampfschichten ist es jedoch gelungen, eine solche Zwischenstruktur, uber die das Kristallwachstum beginnt, nachzuweisen. Das Wachstum der Kristalle beginnt uber einen Kern und geht im weiteren Verlauf in die dreidimensional periodisch geordnete kubisch flachenzentrierte Struktur uber, wobei es zur Zwillingsbildung kommt. In dem vorliegenden Teil III wird versucht, diese Vorgange uber energetische Berechnungen zu bestatigen.

The influence of Fe 2 O 3 , pyruvate and a sealing putty on microbiologically induced corrosion in part of a copper cold-water plumbing system in a large building was investigated. For this purpose, these three substances were injected into the pipe lumen of a non-disinfected and a thermally disinfected section of a tap line affected by microbiologically induced corrosion. It was shown that these substances stimulate, in varying degrees, the microbiological corrosion of copper pipes.

Twins and oriented intergrowths are often caused by structural instabilities. A conflict arises between the highest symmetric and the most favourable energetic structural arrangement. A necessary condition for twin growth is the presence of lattice pseudosymmetries. This was shown with two additional examples, maleic acid and 3,5-dimethylbenzoic acid. Both substances are known practically only as twins. Using lattice-energy calculations, energetic arrangements that are more favourable were found in both cases. These structures explain the transition that can exist between the twin crystal parts. Verzwillingungen und systematische Verwachsungen werden haufig durch strukturelle Instabilitaten hervorgerufen. Es besteht ein Konflikt zwischen der hochstmoglichen symmetrischen und der energetisch gunstigsten Strukturanordnung. Eine notwendige Voraussetzung fur die Bildung von Zwillingen ist das Vorliegen von Gitterpseudosymmetrien. Dies konnte an zwei weiteren Beispielen, der Maleinsaure und der 3,5-Dimethylbenzoesaure, gezeigt werden. Beide Substanzen sind praktisch nur als Zwillinge bekannt. Durch Gitterenergieberechnungen wurden in beiden Fallen energetisch gunstigere Strukturen gefunden, die einen moglichen Ubergang zwischen den Zwillingsindividuen erklaren.

A cytotoxicity assay to determine growth inhibition after a 1-hr treatment with xenobiotics in serum-free medium and subsequent re-incubation in serum-containing medium without test chemicals was characterized and optimized for cytotoxicity screening. Our results indicated that after treatment of human fibroblasts with the test chemicals a 44-hr re-incubation period is most suitable for measuring the growth inhibitory effects of a broad spectrum of chemicals. Applying the assay, the activity to inhibit growth by 10% (log IC 10 ) correlated with the lipophilicity (specified as octanol-water partition coefficient = log K ow ) of 19 xenobiotics. The linear regression coefficient was r = 0.91. This close correlation between toxicity and lipophilicity shows that the test, which avoids long-term incubation in serum-containing medium, is suitable for cytotoxicity screening and structure-activity analysis.

The sensitivity of three methods measuring basal cytotoxicity in human fibroblasts was compared. Cell survival, inhibition of growth and colony-forming ability were measured after 1 hr of incubation with nine environmental chemicals from different substance classes. The sensitivity of the method of determining inhibition of growth was similar to that of the test of colony-forming ability and was double that of a commonly used method to determine cell survival. Linear regression analysis showed that the three methods correlated well with each other, the strongest correlation being between colony-forming ability and growth.

Gypsum was set on polyethylene foil of different origin and on cellophane foil. Experiments were also carried out in an electric field (5-25 kV direct-current). In all cases (especially in the electric field) (010) textures developed on the contact surfaces and were overlapped by a (121) texture. Brinell hardness tests show a greater hardness of the contact areas than those of the upper sides of the samples. Those samples set in an electric field yielded, partly, greater differences. The values, however, diverge greatly.

The present study attempted to determine the effect of dietary supplementation with evening primrose seed oil (EPO) enriched with γ-linolenic acid (GLA, 18:3n-6) on the synthesis of proinflammatory 5-lipoxygenase (5-LOX) metabolites of arachidonic acid (AA, 20:4n-6) by human peripheral neutrophils in adults with atopic dermatitis (AD). After incubation of neutrophils with calcium ionophore A-23187 (10 μM) the 5-LOX products were separated and quantified by reversed-phase high-performance liquid chromatography (RP-HPLC). The results demonstrated that neutrophils of AD patients without therapy generated significantly less LTB4 (P 0.01) and 5-HETE (P < 0.05) was revealed in AD patients after 12 weeks of daily ingestion of 6 g EPO, equivalent to 0.48 g GLA per day, compared with untreated patients (LTB4 609 ± 173 pmol/107 cells vs 390 ± 84 pmol/107 cells and 5-HETE 1463 ± 418 pmol/107 cells vs 9...

The historical approach to assessing health risks of environmental chemicals has been to evaluate them one at a time. In fact, we are exposed every day to a wide variety of chemicals and are increasingly aware of potential health implications. Although considerable progress has been made in the science underlying risk assessments for real-world exposures, implementation has lagged because many practitioners are unaware of methods and tools available to support these analyses. To address this issue, the US Environmental Protection Agency developed a toolbox of cumulative risk resources for contaminated sites, as part of a resource document that was published in 2007. This paper highlights information for nearly 80 resources from the toolbox and provides selected updates, with practical notes for cumulative risk applications. Resources are organized according to the main elements of the assessment process: (1) planning, scoping, and problem formulation; (2) environmental fate and transport; (3) exposure analysis extending to human factors; (4) toxicity analysis; and (5) risk and uncertainty characterization, including presentation of results. In addition to providing online access, plans for the toolbox include addressing nonchemical stressors and applications beyond contaminated sites and further strengthening resource accessibility to support evolving analyses for cumulative risk and sustainable communities.

It is thought that the building units of crystal structures always tend to the highest possible symmetrical arrangements. These arrangements have not to correspond in every case to the energetical most favourable structure. Structures that show this distinct misfit tend to twinning. The examination of pentaerythrite and 1,2,4,5-tetrabromobenzene, two substances usually existing as twins, leads to the finding of structures–by lattice-energy calculations–with a better energy balance, but are not known yet as autonomous phases. Both cases showed arrangements with lower symmetry explaining the transition between the twin individuals. Following this theory the development of crystal twins is based on a structural instability caused by the conflict between the more favourable energetical arrangement and the highest available symmetry. Es wird davon ausgegangen, das die Bausteine in den Kristallstrukturen stets eine hochstmogliche symmetrische Anordnung anstreben. Diese Anordnung mus nicht immer mit der energetisch gunstigsten Struktur ubereinstimmen. Strukturen, bei denen diese Diskrepanz ausgepragt ist, neigen zur Verzwillingung. Anhand von Pentaerythrit und 1,2,4,5-Tetrabrombenzol, die praktisch nur als Zwillinge bekannt sind, wurden durch Gitterenergieberechnungen Strukturen gefunden, die energetisch gunstiger sind, aber als eigenstandige Phasen bisher nicht bekannt sind. In beiden Fallen ergaben sich Anordnungen geringerer Symmetrie. Mit Hilfe dieser Strukturen ist der Ubergang zwischen den Zwillingsindividuen erklarbar. Nach dieser Theorie beruht die Bildung von Kristallzwillingen auf struktureller Instabilitat hervorgerufen durch den Konflikt zwischen energetisch gunstigster Anordnung und hochstmoglicher Symmetrie.

In copper pipework, at work for about four years, blue coloured striations or areas, mainly composed of posnjakite (Cu4(OH)6SO4 · H2O), were found (water chemistry (room temperature): pH = 8.1; SO4 = 24 mg/l; Cl = 16 mg/l; O2 = 10 mg/l). Moreover cuprite, tenorite and malachite were detected on the internal surfaces of copper pipeworks. After the pipework had been in operation for five years, an NaHCO3-dosing apparatus was installed to treat water in all but one branch of the system. In the section with treated water, sulphate formation decreased while malachite formation (Cu2CO3(OH)2) increased. Layer formation can be simulated in electroysis experiments. Normal tap water alone or mixed with bicarbonate is used as an electrolyte.

Background Many studies have demonstrated immunologic changes induced by sublingual immunotherapy (SLIT), but the definitive mechanism of action needs further investigation. Objective To study the immunologic response induced by SLIT in sensitized mice. Methods Timothy grass ( Phleum pratense )–sensitized mice received SLIT for 2, 4, or 6 weeks at 3 different concentrations, including a buffer control. Serum samples and washes of the lungs (bronchoalveolar lavage [BAL]) and the nasal passages (nasal lavage [NAL]) were analyzed for allergen-specific antibodies. T cells were isolated from the spleen and cervical lymph nodes for the analysis of proliferation and cytokine production. Results Sublingual immunotherapy in sensitized mice resulted in a 30-fold increase in antigen specific IgA levels in BAL and NAL fluid compared with buffer-treated mice, whereas antigen specific IgE was undetectable in BAL and NAL fluid in animals treated with SLIT. Furthermore, IgA levels were proportional to the dose and duration of SLIT. Levels of specific IgA in serum correlated with levels in BAL and NAL fluid. Serum IgA levels were proportional to the duration of allergen exposure to the oral mucosa. Conversely, no changes in serum levels of IgE and IgG were induced by SLIT. Proliferation of T cells was increased in mice treated with SLIT compared with nontreated mice. Conclusion High levels of IgA in serum and in BAL and NAL fluid of mice treated with SLIT demonstrate that SLIT induces a mucosal, nonallergic response in sensitized mice.

Background: Sublingual immunotherapy (SLIT) is a clinically effective treatment in both pollen and house dust mite-induced rhinitis and asthma. However, the mechanisms by which this is accomplished are not clear. Objective: The objective of the current study was to establish a mouse model of rhinitis in order to study the effect and mechanisms of SLIT. Methods: Mice were sensitized by intraperitoneal injections of alum-adsorbed Phleum pratense extract. Sensitized mice were SLIT-treated and subsequently challenged intranasally and analysed for clinical symptoms, antibody levels, eosinophilia and T cell response. Results: Intranasal challenge of sensitized mice led to the development of rhinitis characterized by significantly increased sneezing and influx of eosinophils into the nose. Levels of specific IgE were fivefold increased in nasopharyngeal lavage (NAL) fluid and more than doubled in serum. Furthermore, a T-helper type 2 (Th2) like T cell response was observed in local draining lymph nodes. SLIT treatment of sensitized mice reduced sneezing, eosinophilia and IgE levels in the NAL by more than 50%. Moreover, serum levels of IgE and IgG1 as well as T cell response in the draining lymph nodes were also significantly reduced. Treatment for a shorter time or with a lower dose only led to minor reductions of the clinical and immunological parameters, indicating that the effect of SLIT is time and dose dependent. Conclusion: In the present study, we have established a mouse model displaying the hallmarks of allergic rhinitis using a clinically relevant allergen. Using this model, we have demonstrated that SLIT treatment is able to reduce allergic symptoms in a time- and dose-dependent manner.

Human type 1 immediate allergic response symptoms are caused by mediator release from basophils and mast cells. This event is triggered by allergens aggregating preformed IgE Abs bound to the high-affinity receptor (FcεRI) on these cells. Thus, the allergen/IgE interaction is crucial for the cascade leading to the allergic and anaphylactic response. Two genetically engineered forms of the white birch pollen major allergen Bet v 1 with point mutations directed at molecular surfaces have been characterized. Four and nine point mutations led to a significant reduction of the binding to human serum IgE, suggesting a mutation-induced distortion of IgE-binding B cell epitopes. In addition, the mutated allergens showed a decrease in anaphylactic potential, because histamine release from human basophils was significantly reduced. Retained α-carbon backbone folding pattern of the mutated allergens was indicated by x-ray diffraction analysis and circular dichroism spectroscopy. The rBet v 1 mutants were able to induce proliferation of T cell lines derived from birch pollen allergic patients. The stimulation indices were similar to the indices of nonmutated rBet v 1 and natural Bet v 1 purified from birch pollen. The ability of anti-rBet v 1 mutant specific mouse IgG serum to block binding of human serum IgE to rBet v 1 demonstrates that the engineered rBet v 1 mutants are able to induce Abs reactive with nonmodified Bet v 1. rBet v 1 mutants may constitute vaccine candidates with improved efficacy/safety profiles for safer allergy vaccination.

Background: The role of IgG4 during allergen-specific immunotherapy (SIT) is still controversial. The available studies present paramount differences in in vitro techniques, allergens, and clinical outcome parameters. By implementing a sensitive method, and pivotal clinical outcome parameters, we wanted to ascertain the utility of IgG4 as a clinical marker of decreased allergen-specific sensitivity to a common aeroallergen. Methods: Sera were drawn from 23 birch-pollen-allergic patients during a placebo-controlled clinical trial on birch pollen SIT. Seventeen patients received active treatment. Blood samples were drawn at 0, 2, 4, 7, and 30 treatment weeks, and 36 months. The binding activity of autologous IgG, IgG4, IgE, and IgE- and/or IgG-depleted serum to 125I-labelled recombinant Bet v 1 was assessed in a fluid-phase radioimmunoassay. Disease severity was assessed subjectively on a visual analogue scale (VAS), and objectively by intradermal late-phase reaction diameters. Results: Before SIT IgG4 fraction of IgG-allergen binding varied from 4 to 74%, with a median of 36%, increasing to 71% after 36 months. Changes in IgG4 or IgG4/IgG fraction were not correlated to clinical outcome parameters. Changes in IgG allergen binding and VAS were significantly correlated (σ = 0.72; p < 0.05). SIT increased the serum-blocking activity of IgE allergen binding from 25% before SIT to 80% after SIT. No changes were observed in the placebo group. Conclusion: The data suggest that IgG4 per se is a poor marker of decreased allergen-specific sensitivity to birch pollen, both as a single measurement and as delta values.

We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (∼98% CCR3+). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19+ (∼40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant death signaling pathways, which include an increase in levels of Bcl-2 expression, its functional activity, and the release of cytochrome c from the mitochondria into the cytosol. These events initiate a cascade of enzymatic processes of the caspase family, culminating in programmed cell death. Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests a therapeutic modality in the treatment of B cell lymphoma.