Fit for Work and Life-an eight-week program for improvement of functionality and quality of life : A two-stage study

Background: The current two-stage study focused on work integration and quality of life of patients in an acute psychiatric day care unit. There is evidence that a longer absence from work due to illness negatively affects job retention, life satisfaction and clinical prognosis. Furthermore, there are individual supportive methods that proved to be effective in work integration. We therefore developed a specific group program Fit for Work and Life (FWL) for patients in an acute psychiatric day care unit focusing on work integration in the first labor market (in contrast to work in institutions for people with disabilities/second labor market). Methods: Between 2018 and 2020, 62 patients (intervention group; IG) were enrolled in an 8‑week prospective job integration program and compared to 74 patients (control group; CG) who received treatment as usual (partly retrospective survey). Patients of both groups held a job when entering treatment. Main outcome was defined as their working status 4 weeks after the end of treatment as well as self-reported life satisfaction. Results: At the end of treatment (i.e. the week prior to discharge), the IG participants reported higher overall life satisfaction as well as higher health-, self- and living condition-related satisfaction than controls. Functional and clinical improvement during treatment was linked to subsequently returning to work. Functional improvement was further linked to higher life satisfaction. Mediational analysis revealed an indirect path from functional improvement on life satisfaction via working status, i.e. the higher functional improvement during treatment, the higher the chance of successfully returning to work, which in turn increased life satisfaction. Conclusion: Our findings suggest that programs such as FWL are useful interventions for employed patients to improve reintegration into work and life and to help to increase life satisfaction. Keywords: First labor market; Healthcare research; Psychiatric patients; Quality of life; Work integration. = Zusammenfassung: HINTERGRUND: Im Fokus der aktuellen 2‑stufigen Studie standen die berufliche Integration und Lebensqualität von Patienten einer akutpsychiatrischen Tagesklinik. Es gibt Evidenz dafür, dass eine krankheitsbedingte längere Abwesenheit von der Arbeit sich negativ auf den Erhalt des Arbeitsplatzes, die Lebenszufriedenheit und die klinische Prognose auswirkt. Außerdem stehen individuelle Unterstützungsmethoden zur Verfügung, die sich als für die berufliche Integration wirksam erwiesen haben. Daher entwickelten die Autoren eine spezielles Gruppenprogramm „Fit for Work and Life“ (FWL), das sich an Patienten in einer akutpsychiatrischen Tagesklinik richtet und den Schwerpunkt auf die berufliche Integration in den ersten Arbeitsmarkt (im Gegensatz zur Beschäftigung in Einrichtungen für Menschen mit Behinderungen/zweiter Arbeitsmarkt) legt. Methodik: Zwischen 2018 und 2020 wurden 62 Patienten (Interventionsgruppe, IG) in ein 8‑wöchiges prospektives berufliches Integrationsprogramm aufgenommen und mit 74 Patienten verglichen (Kontrollgruppe, KG), die in herkömmlicher Weise behandelt wurden (partiell retrospektive Erhebung). Bei Beginn der Behandlung hatten die Patienten beider Gruppen eine Arbeitsstelle inne. Als Hauptendpunkt wurden der berufliche Status 4 Wochen nach Behandlungsende sowie die Lebenszufriedenheit nach eigenen Angaben definiert. Ergebnisse: Am Ende der Behandlung (d. h. in der Woche vor der Entlassung) gaben die Teilnehmer der IG eine höhere Gesamtlebenszufriedenheit und eine höhere Zufriedenheit in Bezug auf die Gesundheit, die eigene Person und die Lebensbedingungen an als die Kontrollen. Die funktionelle und klinische Verbesserung während der Behandlung stand im Zusammenhang mit der anschließenden Wiederaufnahme der Arbeitstätigkeit. Darüber hinaus war die funktionelle Verbesserung mit einer höheren Lebenszufriedenheit verknüpft. Die Mediationsanalyse ergab einen indirekten Pfad von der funktionellen Verbesserung zur Lebenszufriedenheit über den beruflichen Status, d. h., je größer die funktionelle Verbesserung während der Behandlung war, umso größer war die Chance auf eine erfolgreiche Wiederaufnahme der Arbeitstätigkeit, was wiederum die Lebenszufriedenheit erhöhte. Schlussfolgerung: Die vorliegenden Ergebnisse sind ein Hinweis dafür, dass Programme wie FWL nützliche Interventionen für berufstätige Patienten darstellen, um die Reintegration ins Arbeitsleben zu verbessern und so zur Erhöhung der Lebenszufriedenheit beizutragen. Keywords: First labor market; Healthcare research; Psychiatric patients; Quality of life; Work integration

Fish-derived low molecular weight components modify bronchial epithelial barrier properties and release of pro-inflammatory cytokines

The prevalence of fish allergy among fish-processing workers is higher than in the general population, possibly due to sensitization via inhalation and higher exposure. However, the response of the bronchial epithelium to fish allergens has never been explored. Parvalbumins (PVs) from bony fish are major sensitizers in fish allergy, while cartilaginous fish and their PVs are considered less allergenic. Increasing evidence demonstrates that components other than proteins from the allergen source, such as low molecular weight components smaller than 3 kDa (LMC) from pollen, may act as adjuvants during allergic sensitization. We investigated the response of bronchial epithelial cells to PVs and to LMC from Atlantic cod, a bony fish, and gummy shark, a cartilaginous fish. Polarized monolayers of the bronchial epithelial cell line 16HBE14owere stimulated apically with fish PVs and/-or the corresponding fish LMC. Barrier integrity, transport of PVs across the monolayers and release of mediators were monitored. Intact PVs from both the bony and the cartilaginous fish were rapidly internalized by the cells and transported to the basolateral side of the monolayers. The PVs did not disrupt the epithelial barrier integrity nor did they modify the release of proinflammatory cytokines. In contrast, LMC from both fish species modified the physical and immunological properties of the epithelial barrier and the responses differed between bony and cartilaginous fish. While the barrier integrity was lowered by cod LMC 24 h after cell stimulation, it was increased by up to 2.3-fold by shark LMC. Furthermore, LMC from both fish species increased basolateral and apical release of IL 6 and IL-8, while CCL2 release was increased by cod but not by shark LMC. In summary, our study demonstrated the rapid transport of PVs across the epithelium which may result in their availability to antigen presenting cells required for allergic sensitization. Moreover, different cell responses to LMC derived from bony versus cartilaginous fish were observed, which may play a role in different allergenic potentials of these two fish classes

Critical and direct involvement of the CD23 stalk region in IgE binding

BackgroundThe low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.ObjectiveWe sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.MethodsWe expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated. The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism. By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.ResultsA hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non–N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23. Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.ConclusionOur results provide a new model for the CD23-IgE interaction. We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab

Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses

Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensensitivity disease. It is based on the production of IgE antibodies and T cell responses against per se innocuous antigens (i.e., allergens) and subsequent allergen-induced inflammation in genetically pre-disposed individuals. While allergen exposure in sensitized subjects mainly boosts IgE production and T cell activation, successful allergen-specific immunotherapy (AIT) induces the production of allergen-specific IgG antibodies and reduces T cell activity. Under both circumstances, the resulting allergen-antibody complexes play a major role in modulating secondary allergen-specific immune responses: Allergen-IgE complexes induce mast cell and basophil activation and perpetuate allergen-specific T cell responses via presentation of allergen by allergen presenting cells to T cells, a process called IgE-facilitated antigen presentation (FAP). In addition, they may induce activation of IgE memory B cells. Allergen-induced production of specific IgGs usually exerts ameliorating effects but under certain circumstances may also contribute to exacerbation. Allergen-specific IgG antibodies induced by AIT which compete with IgE for allergen binding (i.e., blocking IgG) inhibit formation of IgE-allergen complexes and reduce activation of effector cells, B cells and indirectly T cells as FAP is prevented. Experimental data provide evidence that by binding of allergen-specific IgG to epitopes different from those recognized by IgE, allergen-specific IgG may enhance IgE-mediated activation of mast cells, basophils and allergen-specific IgE+ B cells. In this review we provide an overview about the role of allergen-specific antibodies in regulating secondary allergen-specific immune responses

Biochemical, Biophysical and IgE-Epitope Characterization of the Wheat Food Allergen, Tri a 37

Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future

In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination

Marker allergens and panallergens in tree and grass pollen allergy

Many allergens from botanically related sources share structural similarities resulting in IgE cross-reactivity. As a consequence, allergens sharing similar structures are often also related on an immunological level, and patients sensitized to one specific allergen may show clinical or in vitro reactivity to structurally similar allergenic proteins of other allergen sources. Different IgE sensitization profiles can be identified in allergic patients according to reactivity to certain allergens. These allergens are defined as marker allergens (Kazemi-Shirazi et al. 2002; Suphioglu 2000; Valenta et al. 2007)

Poor association of allergenspecific antibody, T and Bcell responses revealed with recombinant allergens and a CFSE dilutionbased assay

Background The adaptive immunity underlying allergy comprises two components, the allergenspecific antibody (i.e. IgE, IgG) and the Tcell response. These two components are responsible for different disease manifestations and can be targeted by different therapeutic approaches. Here, we investigated the association of allergenspecific antibody and T as well as Bcell responses in pollenallergic patients using recombinant (r) major birch pollen allergen rBet v 1 and major timothy grass pollen allergen rPhl p 5 as defined antigens. Methods Allergenspecific IgE and IgG antibody responses were determined by ELISA, and allergenspecific T and Bcell responses were measured in peripheral blood mononuclear cells using a carboxyfluoresceindiacetatesuccinimidylester (CFSE) dilution assay. Results CFSE staining in combination with Tcell and Bcellspecific gating allowed discriminating between allergenspecific Tcell and Bcell responses. Interestingly, we identified patients where mainly T cells and others where mainly B cells proliferated in response to allergen stimulation. No association between the level of allergenspecific Ig responses and B or Tcell proliferation was observed. Conclusion Purified recombinant allergens in conjunction with CFSE staining allow the dissection of allergenspecific B and Tcell responses. The dissociation of allergenspecific antibody, and B and Tcell responses may explain the occurrence of selective IgE and Tcellmediated manifestations of allergic inflammation and may be important for the development of diagnostic and therapeutic strategies selectively targeting B cells and T cells.(VLID)484590