Simulating X-ray Absorption Spectroscopy in Challenging Environments: Methodological Insights from Water-Solvated Ammonia and Ammonium Systems.

Core-electron excitations in solvated systems, influenced by solvent geometry and hydrogen bonding, make X-ray absorption spectroscopy (XAS) a valuable tool for assessing solvent-solute interactions. However, calculating XAS spectra with electronic-structure methods has proven challenging due to a delicate interplay between correlation and solvation effects. This study provides a computational procedure for XAS modeling in solvated systems, with water-solvated ammonia and ammonium systems serving as probes. Exploring methodological challenges, we investigate explicit embedding models, specifically the polarizable embedding family, including polarizable density embedding and extended polarizable density embedding. Our linear-response time-dependent density functional theory (LR-TDDFT) XAS calculations reveal the efficiency of this approach, with extended polarizable density embedding emerging as a robust improvement over polarizable density embedding. Contrary to some recent literature, our study challenges the belief that LR-TDDFT cannot accurately describe XAS spectra of ammonia and ammonium solvated in water.

Accuracy of One- and Two-Photon Intensities with the Extended Polarizable Density Embedding Model.

The recently developed extended polarizable density embedding (PDE-X) model is evaluated for the spectroscopic properties of organic chromophores solvated in water, including both one- and two-photon absorption properties. The PDE-X embedding model systematically improves vertical excitation energies over the preceding polarizable density embedding model (PDE). PDE-X shows more modest improvements over existing embedding models for oscillator strengths and two-photon absorption cross-sections, which are more sensitive properties. We argue that the origin of these discrepancies is related to the description of polarization effects, suggesting directions for future development of the embedding model.

Density Functional Tight Binding Theory Approach for the CO2 Reduction Reaction Paths on Anatase TiO2 Surfaces.

Herein, we have investigated the CO2 reduction paths on the (101) anatase TiO2 surface using an approach based on the density functional tight binding (DFTB) theory. We analyzed the reaction paths for the conversion of carbon dioxide to methane by performing a large number of calculations with intermediates placed in various orientations and locations at the surface. Our results show that the least stable intermediate is CO2H and therefore a key bottleneck is the reduction of CO2 to formic acid. Hydrogen adsorption is also weak and would also be a limiting factor, unless very high pressures of hydrogen are used. The results from our DFTB approach are in good agreement with the hybrid functional based density functional theory calculations presented in the literature.

Interventions to prevent iatrogenic anemia: a Laboratory Medicine Best Practices systematic review.

BACKGROUND: As many as 90% of patients develop anemia by their third day in an intensive care unit (ICU). We evaluated the efficacy of interventions to reduce phlebotomy-related blood loss on the volume of blood lost, hemoglobin levels, transfusions, and incidence of anemia. METHODS: We conducted a systematic review and meta-analysis using the Laboratory Medicine Best Practices (LMBP) systematic review methods for rating study quality and assessing the body of evidence. Searches of PubMed, Embase, Cochrane, Web of Science, PsychINFO, and CINAHL identified 2564 published references. We included studies of the impact of interventions to reduce phlebotomy-related blood loss on blood loss, hemoglobin levels, transfusions, or anemia among hospital inpatients. We excluded studies not published in English and studies that did not have a comparison group, did not report an outcome of interest, or were rated as poor quality. Twenty-one studies met these criteria. We conducted a meta-analysis if > 2 homogenous studies reported sufficient information for analysis. RESULTS: We found moderate, consistent evidence that devices that return blood from flushing venous or arterial lines to the patient reduced blood loss by approximately 25% in both neonatal ICU (NICU) and adult ICU patients [pooled estimate in adults, 24.7 (95% CI = 12.1-37.3)]. Bundled interventions that included blood conservation devices appeared to reduce blood loss by at least 25% (suggestive evidence). The evidence was insufficient to determine if these devices reduced hemoglobin decline or risk of anemia. The evidence suggested that small volume tubes reduced the risk of anemia, but was insufficient to determine if they affected the volume of blood loss or the rate of hemoglobin decline. CONCLUSIONS: Moderate, consistent evidence indicated that devices that return blood from testing or flushing lines to the patient reduce the volume of blood loss by approximately 25% among ICU patients. The results of this systematic review support the use of blood conservation systems with arterial or venous catheters to eliminate blood waste when drawing blood for testing. The evidence was insufficient to conclude the devices impacted hemoglobin levels or transfusion rates. The use of small volume tubes may reduce the risk of anemia.

Effectiveness of Laboratory Practices to Reducing Patient Misidentification Due to Specimen Labeling Errors at the Time of Specimen Collection in Healthcare Settings: LMBP™ Systematic Review.

BACKGROUND: Specimen labeling errors have long plagued the laboratory industry putting patients at risk of transfusion-related death, medication errors, misdiagnosis, and patient mismanagement. Many interventions have been implemented and deemed to be effective in reducing sample error rates. The objective of this review was to identify and evaluate the effectiveness of laboratory practices/ interventions to develop evidence based recommendations for the best laboratory practices to reduce labeling errors. CONTENT: The standardized LMBP™ A-6 methods were used to conduct this systematic review. Total evidence included 12 studies published during the time periods of 1980 to September 2015. Combined data from seven studies found that the interventions developed as a result of improved communication and collaboration between the laboratory and clinical staff resulted in substantial decrease in specimen labeling errors (Median relative percent change in labeling errors: -75.86; IQI: -84.77, -58.00). Further data from subset of four studies showed a significant decrease in specimen labeling errors after the institution of the standardized specimen labeling protocols (Median relative percent decrease in specimen labeling errors: -72.45; IQI: -83.25, -46.50). SUMMARY: Based on the evidence included in this review, the interventions that enhance the communication and collaboration between laboratory and healthcare professionals can decrease the specimen identification errors in healthcare settings. However, more research is needed to make the conclusion on the effectiveness of other evaluated practices in this review including training and education of the specimen collection staff, audit and feedback of labeling errors, and implementation of new technology (other than barcoding).

The Impact on Allergy-Related Cells of a Birch Pollen Allergoid, with and without Monophosphoryl Lipid A, in Comparison with the Native Equivalent.

BACKGROUND: The clinical efficacy and safety of allergoid immunotherapy have been demonstrated in clinical trials. However, simultaneous monitoring of the immunological changes by allergoids versus allergens in the cells of the same individual has not been extensively performed, and the impact of concurrent Toll-like receptor 4 (TLR4) ligation has not been specified. METHODS: Three types of birch allergen were utilized: glutaraldehyde-treated allergoid (extract A), the same allergoid plus monophosphoryl lipid A (MPL), i.e., TLR4 ligand (extract A*), and native allergen (extract B). Antigen-specific responses after the in vitro stimulation of blood cells with the extracts were assessed by studying costimulatory receptors on the B cell surface by flow cytometry, cytokine responses by ELISA, and CD63 and CD203c upregulation (basophil activation test) in allergic versus nonallergic subjects. RESULTS: HLA-DR selectively increased upon allergen or allergoid treatment in the allergic group only. The extract types elicited similar cytokine responses, with IL-6 and IL-10 production detected only in certain atopic subjects. The allergoids revealed a strong reduction (100- to <10,000-fold) in basophil activation versus native allergen. Reactivity was undetectable in the basophils from nonallergic subjects. CONCLUSION: The allergenicity of the allergoid employed was sharply reduced when compared to the native allergen, while its immunogenicity was largely retained, especially in the presence of MPL. We also provide further evidence that allergic and nonallergic individuals show preexisting differences in their immune repertoires.

Dietary polyunsaturated fatty acids and non-digestible oligosaccharides reduce dermatitis in mice.

BACKGROUND: Oral administration of specific food ingredients can modify mucosal and systemic inflammatory processes. Such food components are fatty acids or carbohydrates. Nevertheless, little is known about the impact of oral administration of polyunsaturated fatty acids (PUFA) and non-digestible oligosaccharides on allergen-induced dermatitis. METHOD: In this pilot study, skin inflammation was induced by serial epicutaneous OVA applications in OVA-sensitized mice. In parallel, mice were fed with solid food containing arachidonic acid/docosahexaenoic acid (AA/DHA), galactooligosaccharide/polydextrose (GOS/PDX) or their combination. Skin lesions were assessed by clinical skin score, but also skin barrier parameters, immunohistochemical analyses, and local cytokine expression profile. RESULTS: Both dietary AA/DHA and GOS/PDX significantly ameliorated the severity of allergen-induced dermatitis. The clinical improvement upon oral AA/DHA and GOS/PDX supplementation was associated with a reduction in transepidermal water loss and reduced KI-67 expression in the skin. Lesional CD8+ and mast cells were reduced in all treatment groups, but appeared to be most pronounced in combined AA/DHA/GOS/PDX-treated mice. Moreover, in GOS/PDX-treated mice, IFNγ and TGFß expression was increased in skin lesions. CONCLUSION: Dietary supplementation with DHA/AA and GOS/PDX ameliorates symptoms of allergen-induced dermatitis and may thus be beneficial in the dietary management of human atopic eczema.

Effectiveness of practices to reduce blood sample hemolysis in EDs: a laboratory medicine best practices systematic review and meta-analysis.

OBJECTIVE: To complete a systematic review of emergency department (ED) practices for reducing hemolysis in blood samples sent to the clinical laboratory for testing. RESULTS: A total of 16 studies met the review inclusion criteria (12 published and 4 unpublished). All 11 studies comparing new straight needle venipuncture with IV starts found a reduction in hemolysis rates, [average risk ratio of 0.16 (95% CI=0.11-0.24)]. Four studies on the effect of venipuncture location showed reduced hemolysis rates for the antecubital site [average risk ratio of 0.45 (95% CI=0.35-0.57]. CONCLUSIONS: Use of new straight needle venipuncture instead of IV starts is effective at reducing hemolysis rates in EDs, and is recommended as an evidence-based best practice. The overall strength of evidence rating is high and the effect size is substantial. Unpublished studies made an important contribution to the body of evidence. When IV starts must be used, observed rates of hemolysis may be substantially reduced by placing the IV at the antecubital site.

Oral administration of Escherichia coli Nissle 1917 prevents allergen-induced dermatitis in mice.

BACKGROUND: The prevalence of allergies has been linked to Western life style factors including a decrease of microbial exposure. Probiotics, such as Escherichia coli Nissle 1917 (EcN), have been shown to be beneficial for prevention and treatment of several chronic inflammatory diseases. OBJECTIVE: The aim of this study was to investigate the impact of oral EcN administration on development and outcome of allergen-induced dermatitis. METHODS: In sensitized BALB/c mice, skin inflammation was induced by topical allergen application. EcN was administered orally in a preventive manner. Severity of dermatitis was analysed by evaluation of skin score, local cellular and cytokine profile. The systemic immune response was assessed by analysis of immunoglobulins and allergen-dependent cytokine response. RESULTS: Oral EcN administration improved allergen-induced dermatitis dose-dependently. In parallel, a reduction of epidermal thickness and infiltrating immune cells together with an enhanced number of forkhead box P3 (Foxp3)(+) cells and a trend of increased IFNγ, IL-10 and TGFß expression was detected in eczematous skin. In allergen-stimulated splenocytes reduced IL-4 and IFNγ along with an elevated IL-10 production and a tendency to an increased TGFß secretion were observed. CONCLUSIONS: Our findings indicate that EcN alters the local allergen-induced immune response by increase of Foxp3(+) cells and by favouring an immunoregulatory cytokine pattern. Thus, oral administration of EcN might be an effective strategy in prevention and potentially therapy of allergic inflammatory skin diseases.

Inhibition of IgE production by docosahexaenoic acid is mediated by direct interference with STAT6 and NFκB pathway in human B cells.

Nutrition can modify the onset or severity of diseases and recent changes in eating habits are supposed to promote immunoglobulin (Ig) E-dependent disorders. The n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) possesses immunomodulatory properties and has been shown to influence chronic and allergic inflammatory disorders in vivo. Here, we examined the impact of DHA on primary human B cells to elucidate its potential role in direct regulation of IgE production and the underlying mechanisms of action. Therefore, cells were stimulated with anti-CD40/interleukin (IL)-4 in the presence of DHA. Subsequently, Ig production, generation of antibody secreting cells, epsilon-germline transcript (ɛGLT) and activation induced desaminase (AID) expression as well as IgE relevant signaling pathways were analyzed. Our results reveal that DHA inhibits IgE production (75±14%) and, depending on concentration, the differentiation of IgE secreting cells (59±27%). The reduction of IgE is accompanied by a direct inhibition of the switching process indicated by decreased ɛGLT and AID transcription. DHA causes both a reduced CD40 dependent nuclear factor κB-p50 translocation into the nucleus and a decreased IL-4 receptor expression which was associated with a reduction of IL-4 driven signal transducer and activator of transcription 6 phosphorylation. Taken together, DHA inhibits IgE production of human B cells by direct interference with both the CD40 and the IL-4 signaling pathway. The data provide one explanation for the anti-allergic role of DHA at the molecular level.

Liver X receptors control IgE expression in B cells.

B lymphocytes play a fundamental role in the development of IgE-dependent allergic immune reactions. Upon appropriate activation, IgE class switch recombination is initiated in B cells, followed by terminal differentiation to IgE-secreting plasmablasts. This process is controlled by different nuclear receptors, including receptors for vitamin D, retinoids, and peroxisome proliferator-activated receptor-gamma ligands. In this study, we show constitutive expression of the nuclear liver X receptor (LXR)alpha and LXRbeta in peripheral human B cells. Activation of LXRs reduced secreted IgE (-68% +/- 11) in CD40 and IL-4 activated B cells. The production of other isotypes, including IgG, IgM, IgA and B cell homeostatic parameters were not significantly altered by LXR activation. We identified inhibitory action of LXR activation on IgE production involving reduced phosphorylation of JNK and increased membrane CD23 expression (38% +/- 11). The biological significance of our findings was validated by showing that systemic treatment of type I-sensitized BALB/c mice with LXR ligands reduced the serum concentrations of Ag-specific IgE in a dose-dependent manner (maximum, -52% +/- 14). Thus, our data indicates that LXRs are involved in the control of IgE secretion by differentiating B cells.

Systemic PPARgamma ligation inhibits allergic immune response in the skin.

We have shown previously that specific ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit the systemic allergic immune response. The objective of this study was to investigate the impact of PPARgamma-ligand treatment on the local allergic immune response. We established a murine model exhibiting clinical and histological features of AD-like skin lesions with high reproducibility. In this model, the PPARgamma ligand was applied in an either preventive or therapeutic manner via systemic and local routes. The affected skin areas were assessed by standardized skin score, histological analyses, and immunohistochemical examinations. Our data show that systemic application of PPARgamma ligand by a preventive protocol led to significantly reduced onset of eczematous skin lesions. This was confirmed by histology, showing decreased skin thickness accompanied by significantly reduced infiltrations of CD4+ and CD8+ lymphocytes but also mast cells. Additionally, early allergen-specific IgE and IgG1 responses were reduced (day 21/35), whereas IgG2a levels remained unchanged. In conclusion, our results demonstrate that PPARgamma-ligand treatment inhibits not only systemic allergic immune response, but also local allergen-mediated dermatitis. Our findings point to therapeutic strategies, including a PPARgamma-ligand-based treatment.