Chronic inflammatory disease and its treatment during pregnancy

The decision to have children is often coupled with varying degrees of apprehension. Women with chronic disease often worry about how the disease itself or its treatment will affect pregnancy and the fetus. The aim of this thesis was to add to the current knowledge concerning pregnancy and birth outcomes in chronic inflammatory disease. First, we studied pregnancy and delivery complications in women with Crohn’s disease and ulcerative colitis, the main types of inflammatory bowel disease (IBD). By using register data, we constructed a proxy model for disease activity, categorizing women according to (i) no activity, (ii) stable disease and (iii) flaring disease. Compared to women without IBD, women with Crohn’s disease and ulcerative colitis more often delivered by emergency and elective cesarean sections. Women with ulcerative colitis had a higher risk of venous thromboembolism during pregnancy, which seemed to be the highest in women with flaring disease. In the second study, we assessed risks of adverse birth outcomes in women with Crohn’s disease and ulcerative colitis and their infants, by diagnosis and by the disease activity proxy model. Compared to women without IBD, women with Crohn’s disease and ulcerative colitis more often gave birth preterm, particularly those with flaring disease and with thiopurine treatment during pregnancy. Small for gestational age and stillbirth were more common for women with Crohn’s disease, and were also related to flaring disease. The third study focused on anti-tumor necrosis factor (anti-TNF) treatment and birth defects, a relationship which has not been well-studied. Anti-TNF is used to treat IBD and other chronic inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis. We included all infants to women with these diseases in Sweden and Denmark and determined their anti-TNF treatment status in early pregnancy. Infants of the general population were included for a frame of reference for descriptive purposes, while formal comparisons were limited to the women with chronic inflammatory disease. The distribution of birth defects in all three groups was similar and ventricular septal defect, atrial septal defect, congenital hydronephrosis and hypospadias were the most common. Rates for corrective surgery were also similar. Comparing infants to women with chronic inflammatory disease, with and without anti-TNF treatment, the risk of any birth defect or defect of a particular organ-system was slightly but imprecisely increased, and an association could not be determined. In the fourth study, we identified all live-born singleton cases of preterm birth as cases, and births occurring at a later gestational age as their controls, among women with IBD. We found that significant disease activity and treatment with thiopurines or anti-TNF predicted preterm birth. The study illustrated the challenges of confounding by indication. Some misclassification of disease activity was likely not completely avoided, leading to residual confounding and making it impossible to assess the effects of disease activity and immunosuppressive treatment separately. However, weighing the risks of relapsing disease against those of drug treatment, disease activity seems more important to avoid

Printed dose-recording tag based on organic complementary circuits and ferroelectric nonvolatile memories.

We have demonstrated a printed electronic tag that monitors time-integrated sensor signals and writes to nonvolatile memories for later readout. The tag is additively fabricated on flexible plastic foil and comprises a thermistor divider, complementary organic circuits, and two nonvolatile memory cells. With a supply voltage below 30 V, the threshold temperatures can be tuned between 0 °C and 80 °C. The time-temperature dose measurement is calibrated for minute-scale integration. The two memory bits are sequentially written in a thermometer code to provide an accumulated dose record

Проектування та оптимізація конструкцій гумових віброізоляторів силосних конструкцій

Certain intracellular bacteria use the host cell cytosol as the replicative niche. Although it has been hypothesized that the successful exploitation of this compartment requires a unique metabolic adaptation, supportive evidence is lacking. For Francisella tularensis, many genes of the Francisella pathogenicity island (FPI) are essential for intracellular growth, and therefore, FPI mutants are useful tools for understanding the prerequisites of intracytosolic replication. We compared the growth of bacteria taken up by phagocytic or nonphagocytic cells with that of bacteria microinjected directly into the host cytosol, using the live vaccine strain (LVS) of F. tularensis; five selected FPI mutants thereof, i.e., Delta iglA, Delta iglC, Delta iglG, Delta iglI, and Delta pdpE strains; and Listeria monocytogenes. After uptake in bone marrow-derived macrophages (BMDM), ASC(-/-) BMDM, MyD88(-/-) BMDM, J774 cells, or HeLa cells, LVS, Delta pdpE and Delta iglG mutants, and L. monocytogenes replicated efficiently in all five cell types, whereas the Delta iglA and Delta iglC mutants showed no replication. After microinjection, all 7 strains showed effective replication in J774 macrophages, ASC(-/-) BMDM, and HeLa cells. In contrast to the rapid replication in other cell types, L. monocytogenes showed no replication in MyD88(-/-) BMDM and LVS showed no replication in either BMDM or MyD88(-/-) BMDM after microinjection. Our data suggest that the mechanisms of bacterial uptake as well as the permissiveness of the cytosolic compartment per se are important factors for the intracytosolic replication. Notably, none of the investigated FPI proteins was found to be essential for intracytosolic replication after microinjection.Originally included in thesis in manuscript form.</p

The role of photosynthesis in choosing optimal agro-technical factors of autumn canola production

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Critical role of a sheath phosphorylation site on the assembly and function of an atypical type VI secretion system

The bacterial pathogen Francisella tularensis possesses a non-canonical type VI secretion system (T6SS) that is required for phagosomal escape in infected macrophages. KCl stimulation has been previously used to trigger assembly and secretion of the T6SS in culture. By differential proteomics, we found here that the amounts of the T6SS proteins remained unchanged upon KCl stimulation, suggesting involvement of post-translational modifications in T6SS assembly. A phosphoproteomic analysis indeed identified a unique phosphorylation site on IglB, a key component of the T6SS sheath. Substitutions of Y139 with alanine or phosphomimetics prevented T6SS formation and abolished phagosomal escape whereas substitution with phenylalanine delayed but did not abolish phagosomal escape in J774-1 macrophages. Altogether our data demonstrated that the Y139 site of IglB plays a critical role in T6SS biogenesis, suggesting that sheath phosphorylation could participate to T6SS dynamics

Antipsychotic drug use in pregnancy: A multinational study from ten countries

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents

Characterization of the outer membrane proteome of Francisella noatunensis subsp. orientalis

Aims The aims of the current study were to characterise the outer membrane proteins (OMPs) of Francisella noatunensis subsp. orientalis (Fno) STIR‐GUS‐F2f7, and identify proteins recognised by sera from tilapia, Oreochromis niloticus, (L) that survived experimental challenge with Fno. Methods and Results The composition of the OMPs of a virulent strain of Fno (STIR‐GUS‐ F2f7), isolated from diseased red Nile tilapia in UK, was examined. The sarcosine‐insoluble OMP fraction was screened with tilapia hyper‐immune sera by western blot analysis following separation of the proteins by 1D SDS‐PAGE. Liquid chromatography‐electrospray ionisation‐tandem mass spectrometry (LC‐ESI‐MS/MS) was used to identify the various proteins present in the OMP profile. Two hundred and thirty‐nine proteins were identified, of which 44 were found in the immunogenic band recognised by the tilapia hyperimmune serum. In silico analysis was performed to predict the function and location of the OMPs identified by MS. Conclusions Using a powerful proteomic‐based approach in conjugation with western immunoblotting, proteins comprising the outer membrane fraction of Fno STIR‐GUS‐F2f7 were identified, catalogued and screened for immune recognition by tilapia sera. Significance and Impact of the study The current study is the first report on the characterisation of Fno OMPs. The findings here provide preliminary data on bacterial surface proteins that exist in direct contact with the host's immune defences during infection and offer an insight into the pathogenesis of Fno