Respiratory health effects of indoor microbial exposure : a contribution to the development of exposure assessment methods

The studies described in this thesis validated an existing method to measure bacterial endotoxin and explored new methods for measuring mold components in the environment, particularlyβ(1→3)-glucans and extracellular polysaccharides (EPS). These assays were used to study levels of microbial components in the home and occupational environment, and to investigate their relationships with respiratory health in children or workers, respectively.It was shown that results of endotoxin measurements may differ considerably between laboratories when different sampling, extraction, and storage procedures are employed. Highest yields were found when samples were extracted with 0.05% Tween-20 in water. Repeated freezing and thawing resulted in a considerable endotoxin loss.β(1→3)-glucan, endotoxin and EPS from Aspergillus and Penicillium spp. (EPS- Asp/Pen ) were readily detectable in house dust samples. Endotoxin andβ(1→3)-glucan levels were, at least for living room floors, significantly associated with certain home characteristics, particularly heating system and/or age of the home. Bothβ(1→)-glucan and EPS- Asp/Pen were significantly but only weakly correlated with culturable fungi in house dust. Living room floor concentrations of EPS- Asp/Pen were positively associated with occupant-reported home dampness and respiratory symptoms in children, while no such associations were found for bedroom and mattress concentrations.In another study among children it was shown thatβ(1→3)-glucan in house dust from living room floors was strongly associated with peak flow (PEF) variability, particularly in atopic and/or asthmatic children. No associations were found forβ(1→3)-glucan levels on bedroom floors and mattresses. Unadjusted regression models showed that endotoxin levels were also significantly associated with PEF variability, while after adjusting for other known risk factors no significant association was found. A study among compost workers showed that microbial exposure induces acute and possibly chronic inflammation in the upper airways with a mechanism that suggests non-immune or possibly type III but not type I allergic inflammation.It is concluded that the studies reported in this thesis contribute to new methods for microbial exposure assessment that offer advantages for use in epidemiological studies compared to traditionally employed culture-based methods.</p

Protease inhibitors prevent plasminogen-mediated, but not pemphigus vulgaris-induced, acantholysis in human epidermis

Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. It is caused by autoantibodies directed against desmosomes, which are the principal adhesion structures between epidermal keratinocytes. Binding of autoantibodies leads to the destruction of desmosomes resulting in the loss of cell-cell adhesion (acantholysis) and epidermal blisters. The plasminogen activator system has been implicated as a proteolytic effector in pemphigus. We have tested inhibitors of the plasminogen activator system with regard to their potential to prevent pemphigus-induced cutaneous pathology. In a human split skin culture system, IgG preparations of sera from pemphigus vulgaris patients caused histopathologic changes (acantholysis) similar to those observed in the original pemphigus disease. All inhibitors that were tested (active site inhibitors directed against uPA, tPA, and/or plasmin; antibodies neutralizing the enzymatic activity of uPA or tPA; substances interfering with the binding of uPA to its specific cell surface receptor uPAR) failed to prevent pemphigus vulgaris IgG-mediated acantholysis. Plasminogen-mediated acantholysis, however, was effectively antagonized by the synthetic active site serine protease inhibitor WX-UK1 or by p-aminomethylbenzoic acid. Our data argue against applying anti-plasminogen activator/anti-plasmin strategies in the management of pemphigus

Review of methods applicable to the assessment of mold exposure to children.

This article presents discussion of the assessment of the exposure of children to fungi, substances derived from fungi, and the environmental conditions that may lead to exposure. The principles driving investigations of fungal contamination and subsequent exposure are presented as well as guidelines for conducting these investigations. A comprehensive description of available research sampling and analysis techniques is also presented

Discrepancy between self-perceived mycophenolic acid-associated diarrhea and stool water content after kidney transplantation

BACKGROUND: Diarrhea is a well-known side effect of mycophenolic acid (MPA) use in kidney transplant recipients (KTRs). It is unknown whether self-reported diarrhea using the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) corresponds to stool water content and how both relate to MPA usage. METHODS: MTSOSD-59R questionnaires filled out by 700 KTRs from the TransplantLines Biobank and Cohort Study(NCT03272841) were analyzed and compared with stool water content. Stool samples(N=345) were freeze-dried and a water content ≥80% was considered diarrhea. RESULTS: Self-perceived diarrhea was reported by 46%, while stool water content ≥80% was present in 23% of KTRs. MPA use was not associated with self-perceived diarrhea (odds ratio(OR) 1.32; 95% confidence interval(CI), 0.87-1.99, P=0.2), while it was associated with stool water content ≥80% (OR 2.88; 95%CI, 1.41-5.89, P=0.004), independent of potential confounders. Adjustment for prior MPA discontinuation because of severe diarrhea, uncovered an association between MPA use and self-perceived diarrhea (OR 1.80; 95%CI, 1.13-2.89, P=0.01). CONCLUSIONS: These results suggest that reporting bias could add to the discrepancy between both methods for diarrhea assessment. We recommend use of objective biomarkers or more extensive questionnaires which assess information on stool frequency and stool consistency, to investigate post-transplantation diarrhea

Vortex pinning by natural defects in thin films of YBa2Cu3O7−δ

Although vortex pinning in laser-ablated YBa2Cu3O7−δ films on (100) SrTiO3 is dominated by threading dislocations, many other natural pinning sites are present. To identify the contribution from twin planes, surface corrugations and point defects, we manipulate the relative densities of all defects by post-annealing films with various as-grown dislocation densities, ndisl. While a universal magnetic field B dependence of the transport current density js(B, T) is observed (independently of ndisl, temperature T and the annealing treatment), the defect structure changes considerably. Correlating the microstructure to js(B, T), it becomes clear that surface roughness, twins and point defects are not important at low magnetic fields compared to linear defect pinning. Transmission electron microscopy indicates that threading dislocations are not part of grain boundaries nor are they related to the twin domain structure. We conclude that js(B, T) is essentially determined by pinning along threading dislocations, naturally induced during the growth process. Even in high magnetic fields, where the vortex density outnumbers ndisl, it appears that linear defects stabilize the vortex lattice by means of the vortex–vortex interaction.

Національна безпека України в епоху глобалізації

Розглядається сучасний проект Стратегії національної безпеки України “Україна в світі, що змінюється”, розроблений Національним інститутом стратегічних досліджень. Визначаються слабкі місця і невизначеності цієї стратегії. Проаналізовано реальний стан та перспективи впровадження цього проекту.In the article the modern is examined project of Strategy of national safety of Ukraine “Ukraine in the world that changes” worked out by the National institute of strategic. The weak locations and vaguenesses of this strategy are determined. An author analyses the real state and prospects of introduction of this project

Extended spectrum β-lactamase-and AmpC β-lactamase-producing Enterobacterales associated with urinary tract infections in the New Zealand community: A case-control study.

(c) The Author/sOBJECTIVES: To assess whether having a pet in the home is a risk factor for community-acquired urinary tract infections associated with extended spectrum β-lactamase (ESBL)- or AmpC β-lactamase (ACBL)- producing Enterobacterales. METHODS: An unmatched case-control study was conducted between August 2015 and September 2017. Cases (n=141) were people with community-acquired urinary tract infection (UTI) caused by ESBL- or ACBL- producing Enterobacterales. Controls (n=525) were recruited from the community. A telephone questionnaire on pet ownership, and other factors was administered, and associations were assessed using logistic regression. RESULTS: Pet ownership was not associated with ESBL- or ACBL-producing Enterobacterales related human UTIs. A positive association was observed for recent antimicrobial treatment, travel to Asia in the previous year, and a doctor's visit in the previous six months. Among isolates with an ESBL-/ACBL-producing phenotype 126/134 (94%) were Escherichia coli, with sequence type (ST) 131 being the most common (47/126). CONCLUSIONS: Companion animals in the home were not found to be associated with ESBL- or ACBL-producing Enterobacterales related community-acquired UTI in New Zealand. Risk factors included overseas travel, recent antibiotic use, and doctor visits.Published onlin

Airborne Mold and Endotoxin Concentrations in New Orleans, Louisiana, after Flooding, October through November 2005

BACKGROUND: The hurricanes and flooding in New Orleans, Louisiana, in October and November 2005 resulted in damp conditions favorable to the dispersion of bioaerosols such as mold spores and endotoxin. OBJECTIVE: Our objective in this study was to assess potential human exposure to bioaerosols in New Orleans after the flooding of the city. METHODS: A team of investigators performed continuous airborne sampling for mold spores and endotoxin outdoors in flooded and nonflooded areas, and inside homes that had undergone various levels of remediation, for periods of 5–24 hr during the 2 months after the flooding. RESULTS: The estimated 24-hr mold concentrations ranged from 21,000 to 102,000 spores/m(3) in outdoor air and from 11,000 to 645,000 spores/m(3) in indoor air. The mean outdoor spore concentration in flooded areas was roughly double the concentration in nonflooded areas (66,167 vs. 33,179 spores/m(3); p < 0.05). The highest concentrations were inside homes. The most common mold species were from the genera of Cladosporium and Aspergillus/Penicillium; Stachybotrys was detected in some indoor samples. The airborne endotoxin concentrations ranged from 0.6 to 8.3 EU (endo-toxin units)/m(3) but did not vary with flooded status or between indoor and outdoor environments. CONCLUSIONS: The high concentration of mold measured indoors and outdoors in the New Orleans area is likely to be a significant respiratory hazard that should be monitored over time. Workers and returning residents should use appropriate personal protective equipment and exposure mitigation techniques to prevent respiratory morbidity and long-term health effects