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This study investigates the effects of a linguistic self-distancing technique during reflection on affect, challenge versus threat appraisal, and anticipatory stress for individuals in high-stress occupations. Research in the laboratory suggests that reflections using non-first-person pronouns can reduce emotional reactivity to stressors, improve challenge appraisal, and reduce stress anticipation for future stressors. This study was conducted through an online questionnaire including a short reflection task. Participants were asked to reflect on a recent stressful work event either from a self-distanced or a self-immersed perspective. Self-assessments of global affect were collected pre- and post-reflection, while post-reflection reports of positive and negative affect in particular, as well as challenge versus threat appraisal and anticipatory stress were recorded. General measures of work stress and emotion regulation skills were included as covariates. A repeated-measures ANCOVA revealed no significant changes in global affect at the group level, but the interaction of gender and time of assessment showed a significant decrease in global affect scores only for female participants in the control group. Univariate ANCOVAs further showed no significant effects concerning positive and negative affect scores, or challenge versus threat appraisal. Interestingly, there was a significant group difference in anticipatory stress, revealing higher stress scores for the self-distanced over the self-immersed condition. The results contradict current research and emphasise the need to consider gender-specific differences in the effects of self-distanced reflections. Implications towards their suitability in unguided, naturalistic contexts and for regulating occupational stress in specific will be discussed with regards to methodological limitations.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes,"remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

Human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV), which are critical for the structure of antibodies that identify and neutralize pathogenic invaders as a part of the adaptive immune system. Because of its highly repetitive sequence composition, the IGH locus has been particularly difficult to assemble or genotype when using standard short-read sequencing technologies. Here, we introduce ImmunoTyper-SR, an algorithmic tool for the genotyping and CNV analysis of the germline IGHV genes on Illumina whole-genome sequencing (WGS) data using a combinatorial optimization formulation that resolves ambiguous read mappings. We have validated ImmunoTyper-SR on 12 individuals, whose IGHV allele composition had been independently validated, as well as concordance between WGS replicates from nine individuals. We then applied ImmunoTyper-SR on 585 COVID patients to investigate the associations between IGHV alleles and anti-type I IFN autoantibodies, which were previously associated with COVID-19 severity.

Darstellung des Themas: Folgen eines Schädelhirntraumas können grosse Herausforderungen bei der Rückkehr ins Arbeitsleben mit sich bringen. Für viele Betroffene ist die berufliche Integration ein wichtiges Rehabilitationsziel. Obwohl die Ergotherapie Personen in diesen Herausforderungen gut unterstützen kann, ist sie in der Schweiz in diesem Arbeitsbereich selten anzutreffen. Ziel: Das Ziel der Bachelorarbeit ist es, aufzuzeigen und zu begründen, welches Wissen und welche Fertigkeiten nach dem sogenannten «Rollen-Kompetenz-Profil» die Ergotherapie in der Schweiz bei der beruflichen Integration von erwachsenen Menschen nach erlittenem Schädelhirntrauma einbringen und welche Aufgaben sie dabei übernehmen kann. Methode: Mittels einer systematischen Literaturrecherche wurden fünf Hauptstudien ermittelt und anschliessend kritisch gewürdigt. Die Autorinnen teilten die Studienergebnisse unabhängig voneinander den verschiedenen Rollen des Rollen-Kompetenz-Profils zu. Daraus wurden mögliche ergotherapeutische Aufgaben abgeleitet sowie Kompetenzen beschrieben, welche die Ergotherapie einbringen kann. Relevante Ergebnisse: Es zeigt sich, dass die Ergotherapie besonders in den Bereichen Evaluation, Unterstützen des Selbstfindungsprozesses, Trainieren der Fertigkeiten und Funktionen sowie Arbeitsplatzanpassungen ihr spezifisches Fachwissen einbringen kann. Schlussfolgerung: Die Ergotherapie kann als Teil des interprofessionellen Behandlungsteams mit ihrer betätigungsfokussierten und ganzheitlichen Herangehensweise einen Mehrwert in der beruflichen Integration von Menschen nach erlittenem Schädelhirntrauma erbringen.

Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1–6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the mRNA expression of previously determined hypoxia markers to define the temporal adaptation of MM cells to chronic hypoxia. Subsequent analyses of the global proteome in MM cells and the stromal cell line HS-5 revealed hypoxia-dependent regulation of proteins, which directly or indirectly upregulate glycolysis. In addition, chronic hypoxia led to MM-specific regulation of nine distinct proteins. One of these proteins is the cysteine protease legumain (LGMN), the depletion of which led to a significant growth disadvantage of MM cell lines that is enhanced under hypoxia. Thus, herein, we report a methodologic strategy to examine MM cells under physiologic hypoxic conditions in vitro and to decipher and study previously masked hypoxia-specific therapeutic targets such as the cysteine protease LGMN.

Bloodstream infections (BSI) are a frequent complication in patients with hematological and oncological diseases. However, the impact of different bacterial species causing BSI and of multiple BSI remains incompletely understood. We performed a retrospective study profiling 637 bacterial BSI episodes in hematological and oncological patients. Based on the 30-day (30d) overall survival (OS), we analyzed different types of multiple BSI and grouped BSI-associated bacteria into clusters followed by further assessment of clinical and infection-related characteristics. We discovered that polymicrobial BSI (different organisms on the first day of a BSI episode) and sequential BSI (another BSI before the respective BSI episode) were associated with a worse 30d OS. Different bacterial groups could be classified into three BSI outcome clusters based on 30d OS: favorable (FAV) including mainly common skin contaminants, Escherichia spp. and Streptococcus spp.; intermediate (INT) including mainly Enterococcus spp., vancomycin-resistant Enterococcus spp., and multidrug-resistant gram-negative bacteria (MDRGN); and adverse (ADV) including MDRGN with an additional carbapenem-resistance (MDRGN+CR). A polymicrobial or sequential BSI especially influenced the outcome in the combination of two INT cluster BSI. The presence of a polymicrobial BSI and the assignment into the BSI outcome clusters were identified as independent risk factors for 30d mortality in a Cox multivariate regression analysis. The assignment to a BSI outcome cluster and the differentiated perspective of multiple BSI open new insights into the prognosis of patients with BSI and should be further validated in other patient cohorts.

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell diseases leading to an insufficient formation of functional blood cells. Disease-immanent factors as insufficient erythropoiesis and treatment-related factors as recurrent treatment with red blood cell transfusions frequently lead to systemic iron overload in MDS and AML patients. In addition, alterations of function and expression of proteins associated with iron metabolism might are increasingly recognized to be pathogenetic factors and potential vulnerabilities of these diseases. Iron is known to be involved in multiple intracellular and extracellular processes. It is essential for cell metabolism as well as for cell proliferation and closely linked to the formation of reactive oxygen species. Therefore, iron can influence the course of clonal myeloid disorders, the leukemic environment and the occurrence as well as the defense of infections. Imbalances of iron homeostasis may induce cell death of normal but also of malignant cells. New potential treatment strategies utilizing the importance of the iron homeostasis include iron chelation, modulation of proteins involved in iron metabolism, induction of leukemic cell death via ferroptosis and exploitation of iron proteins for the delivery of antileukemic drugs. Here, we provide a summary of some of the latest findings about the function, the prognostic impact and potential treatment strategies of iron in patients with MDS and AML.

Global investments in online advertising rise quickly but Internet users often avoid looking at ads due to established banner blindness. Demographic targeting is expected to overcome this tendency by attracting users' attention to more self-relevant ad content. However, little is known about the effect of demographically targeted versus non-targeted ads on users' actual attention allocation during exposure to webpages. The present study aimed to further fill this empirical gap by clarifying whether demographic targeting attracts visual attention and to exploratively examine whether it also affects brand attitude and website evaluation, as suggested by previous studies. Eye tracking data revealed that demographic targeting can have medium- to large-sized effects on several eye movement parameters when inter net users are in a free-viewing mode. In contrast, demographic targeting did not influence brand attitude and website evaluation. We conclude that attention for personally relevant advertisement can be strong. However, attention, although being a necessary condition for subsequent judgment formation according to the model of human information processing, is not sufficient to elicit positive effects at the level of subjective judgments.

Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a potentially curative treatment option for relapsed and refractory lymphomas. Obesity displays an emerging epidemic risk factor for global mortality and is associated with an increased mortality in cancer patients. To date, the impact of obesity on the outcome of lymphoma patients undergoing auto-HSCT is understudied. We conducted a retrospective single-center study assessing 119 lymphoma patients who underwent auto-HSCT. Overall survival (OS) served as the primary endpoint whereas progression free survival (PFS), cumulative incidence of non-relapse related mortality (NRM) and cumulative incidence of relapse were analyzed as secondary endpoints. Obese patients (Body mass index, BMI≥30) had significantly lower OS (45.3% vs. 77.9%; p = 0.005) and PFS (29.8% vs. 67.2%; p<0.001) compared to non-obese patients at 48 months post-transplantation. The cumulative incidence of NRM displayed no significant differences while the cumulative incidence of relapse was significantly increased in patients with BMI≥30 (66.2% vs. 21.5%; p<0.001). Patients with a BMI<25 and overweight patients (BMI 25–30; 76.1% vs. 80.9%; p = 0.585), showed no significant difference in OS, whereas patients with BMI≥30 exhibited significant lower OS when compared to either of both groups (76.1% vs. 45.3%; p = .0.021 and 80.9% vs. 45.3%; p = 0.010). Furthermore, in a multivariate analysis, obesity was identified as an independent risk factor for death (Hazard ratio 2.231; 95% CI 1.024 to 4.860; p = 0.043). Further studies are needed to evaluate the reasons for the higher relapse rate causing higher mortality in obese patients.

BACKGROUND AND PURPOSE Non-allergic angio-oedema is a life-threatening disease mediated by activation of bradykinin type 2 receptors (B-2 receptors). The aim of this study was to investigate whether activation of B-2 receptors by endogenous bradykinin contributes to physiological extravasation. This may shed new light on the assumption that treatment with an angiotensin converting enzyme inhibitor (ACEi) results in an alteration in the vascular barrier function predisposing to non-allergic angio-oedema. EXPERIMENTAL APPROACH We generated a new transgenic mouse model characterized by endothelium-specific overexpression of the B-2 receptor (B2(tg)) and established a non-invasive two-photon laser microscopy approach to measure the kinetics of spontaneous extravasation in vivo. The B2(tg) mice showed normal morphology and litter size as compared with their transgene-negative littermates (B2(n)). KEY RESULTS Overexpression of B-2 receptors was functional in conductance vessels and resistance vessels as evidenced by B-2 receptor-mediated aortic dilation to bradykinin in presence of non-specific COX inhibitor diclofenac and by significant hypotension in B2(tg) respectively. Measurement of dermal extravasation by Miles assay showed that bradykinin induced extravasation was significantly increased in B2(tg) as compared with B2(n). However, neither endothelial overexpression of B-2 receptors nor treatment with the ACEi moexipril or B-2 antagonist icatibant had any effect on spontaneous extravasation measured by two-photon laser microscopy. CONCLUSIONS AND IMPLICATIONS Activation of B-2 receptors does not appear to be involved in spontaneous extravasation. Therefore, the assumption that treatment with an ACEi results in an alteration in the physiological vascular barrier function predisposing to non-allergic angio-oedema is not supported by our findings.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure to acute myeloid leukemia (AML) patients. However, infections with commensal bacteria are an important cause for non-relapse mortality (NRM). We have previously described the impact of multidrug-resistant organism (MDRO) colonization on the survival of allo-HSCT patients. In the aforementioned publication, according to consensus, we there did not consider the opportunistic gram-negative bacterium Stenotrophomonas maltophilia (S. maltophilia) to be an MDRO. Since rate of S. maltophilia colonization is increasing, and it is not known whether this poses a risk for allo-HSCT patients, we here analyzed here its effect on the previously described and now extended patient cohort. We report on 291 AML patients undergoing allo-HSCT. Twenty of 291 patients (6.9%) were colonized with S. maltophilia. Colonized patients did not differ from non-colonized patients with respect to their age, remission status before allo-HSCT, donor type and HSCT-comorbidity index. S. maltophilia colonized patients had a worse overall survival (OS) from 6 months up to 60 months (85% vs. 88.1% and 24.7% vs. 59.7%; p = 0.007) due to a higher NRM after allo-HSCT (6 months: 15% vs. 4.8% and 60 months: 40.1% vs. 16.2% p = 0.003). The main cause of mortality in colonized patients was infection (46.2% of all deaths) and in non-colonized patients relapse (58.8% of all deaths). 5/20 colonized patients developed an invasive infection with S. maltophilia. The worse OS after allo-HSCT due to higher infection related mortality might implicate the screening of allo-HSCT patients for S. maltophilia and a closer observation of colonized patients as outpatients.

Background: Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders. Methodology/Principal Findings: We applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children’s Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn’s disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity). Conclusions/Significance: Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients., Natural Sciences and Engineering Research Council of Canada (Award NSERC PGS D), National Institutes of Health (U.S.) (1-R21-A1084032-01A1)

Polyhedral Oligomeric Silsesquioxane (POSS) cages [RSiO(sub 1.5)]n are a class of nano-particles that are being exploited as property modifiers to virtually every type of polymer imaginable. The most common of these materials are the R8Si8O12 derivatives (also known as the T(sub 8's)), as the octomeric cage is preferentially formed in almost all synthetic pathways reported. However, well-defined oligomeric cages with n = 6, 10, 12 or 14 are also known and their polyhedral structures proven with single crystal X-ray crystallography., For presentation at the American Chemical Society National Meeting held in Washington, DC on 16-20 August 2009.

Polyhedral oligomeric silsesquioxane (POSS) has generated much interest in the development of novel nanomaterials. The organic groups attached to the silicon atoms in the POSS cage can serve many different functions. It has been shown that POSS copolymers exhibit different rheological properties when the organic group is changed in a copolymer. In this work, we examine the effects of varying the organic groups (R = c-C5H9: denoted as Cp, i-C4H9: i-Bu, C3H4F3: FPr) on propylmethacryl POSS molecule copolymerized with n-butyl methacrylate. i-Bu groups increase the free volume in the copolymer whereas the Cp and FPr groups appear to interact thereby reinforcing the soft polymer., Presented at the American Chemical Society National Meeting and Exposition (237th) held in Salt Lake City, Utah on 22-26 March 2009.

Dark blue (C183) ungrained cloth; rectangular design of light green stylized leafy vines and berries over gilt lettering; motif repeated on spine; top edges gilt, untrimmed. H: 19.5 cm.; W: 13.3 cm.; D: 3 cm.

Three heterocystous cyanobacterial strains (two Richelia intracellularis: RintHH01, RintRC01, Calothrix rhizosoleniae: CalSC01) are known to form highly specific, intimate associations with several lineages of diatoms. Collectively these symbioses are unique since the cellular location varies from internal, partially integrated, and fully external; hence the immediate environment of the symbiont differs. We investigated the environmental gene expression levels of the three strains using a targeted mRNA microarray comprised of 748 genes on environmental samples collected in the South China Sea. Approximately half of the total genes (47%, 354 of the 748 genes) were expressed above background. The most highly transcribed genes were involved in photosynthesis, N2 fixation and potassium homeostasis, and strain differences were identifiable. The most important environmental parameters on the symbiont gene expression levels were fluorescence, temperature and beam transmission. However, salinity and oxygen impacted gene expression levels of one symbiont strain, RintHH01 differently (positively), possibly due to its different cellular location. Our results suggest that differences in gene expression patterns and environmental conditions influence the three closely related symbiont strains, and are likely related to their cellular location in their respective host diatoms.