Fibrinolytic and coagulative activities of Yersinia pestis

Peer reviewe

Real-world treatment outcomes in multiple myeloma: Multicenter registry results from Finland 2009-2013

Outcomes for patients with multiple myeloma (MM) have improved with the advent of novel therapies, however, real-world evidence of outcomes in clinical practice is scarce. We conducted a multi-center registry study to build a reliable picture of treatment and patient outcomes in Finland. The aim of this study was also to understand any methodological challenges in assessing treatment outcomes using disease registry data. Methods: We carried out a retrospective, observational study using data from the national Finnish Hematology Registry (FHR) to provide real-world evidence of outcomes for all adult patients diagnosed with and treated for MM between 2009–2013 at one of the six regional hospitals, with at least six months of recorded follow-up. Patients were identified within the FHR by applying eligibility criteria of a diagnosis of MM and verifiable records of medical treatment and lines of treatment during the study period. Patients receiving allogenic stem cell transplantation were excluded from the cohort, as were individuals who only had monoclonal gammopathy of undetermined significance diagnosis and patients who had not initiated treatment during this period. Kaplan Meier curves were used to calculate overall survival and time to next treatment. Stratification was carried out by drug status (conventional/novel) and by autologous stem cell transplant (ASCT) status. Results: A total of 321 patients met the inclusion criteria and were included in this study. Overall survival (OS) was longest in patients who received first-line novel therapy and ASCT (median not reached during 60-month follow-up) versus 46.2 months for novel first-line therapy without ASCT and 25.6 months for first-line conventional therapy without ASCT. Similarly, median time to next treatment were 33.9 months, 12.6 months and 7.8 months, respectively. Conclusions: The adoption of novel treatments in MM in Finland has had substantial impact on patient outcomes. Given the reality of complex treatment combinations for MM and relatively low patient numbers, assessing individual treatment effectiveness will require substantial cohort sizes and advanced, collaborative analytics on an international scale</p

Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus strains and their comparison with strain GG

Peer reviewe

Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus strains and their comparison with strain GG

Peer reviewe

Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.Peer reviewe

Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

<p>Abstract</p> <p>Background</p> <p>Acute phase proteins haptoglobin (Hp), serum amyloid A (SAA) and lipopolysaccharide binding protein (LBP) have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with <it>Escherichia coli </it>and to evaluate the possible carry-over effect when same animals are used in an experimental model.</p> <p>Methods</p> <p>Mastitis was induced with a dose of 1500 cfu of <it>E. coli </it>in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp), serum amyloid A (SAA) and lipopolysaccharide binding protein (LBP) were determined in serum and milk.</p> <p>Results</p> <p>In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the <it>E. coli </it>infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by <it>E. coli</it>.</p> <p>Conclusion</p> <p>Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary induction of the same animals with <it>E. coli </it>is used in cross-over studies, the interval between challenges should be longer than 2 weeks, due to the carry-over effect from the first infection.</p

Schulische Netzwerke als Professionalisierungsstrategie. Erfahrungen und Forschungsbefunde aus dem Projekt „Schulen im Team“.

Berkemeyer N, Järvinen H, Otto J. Schulische Netzwerke als Professionalisierungsstrategie. Erfahrungen und Forschungsbefunde aus dem Projekt „Schulen im Team“. In: Kobarg M, Fischer C, Dalehefte M, Trepke F, Menk M, eds. Lehrerprofessionalisierung wissenschaftlich begleiten. Strategien und Methoden. Münster: Waxmann; 2012: 117-130

Deposition of IgG, IgM, C3b and MAC.

<p>Bacteria prepared as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027546#pone-0027546-g001" target="_blank">Figure 1A</a> were mock treated with DPBS (no serum) or incubated with 10% HIS or 10% NHS for 10 min at 37°C. IgG and IgM binding was measured by FACS analysis using goat anti-human IgG antibodies and rabbit anti-human IgM, respectively. Bound C3b was detected using a polyclonal rabbit anti-human C3c antibody, which recognizes the C3b, iC3b and native C3 forms. MAC deposition was detected by a mouse-monclonal antibody specific for the C5b-9 complex. MFI and FOB (fold over background, the value obtained when the MFI value from 10% NHS is divided by the corresponding value from 10% HIS) values are indicated. Representative data of an experiment performed three times is shown.</p

Localization of the Rck binding site on C4BP.

<p>A. BL21(DE3) pRck grown as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027546#pone-0027546-g001" target="_blank">Figure 1A</a> were mock treated (DPBS only) or incubated with purified C4BP or recombinant C4BP deletion mutants (10 µg/ml), each with a single individual CCP deletion (Δ1-8). Bound C4BP (wt or mutant) was detected with sheep polyclonal anti-human C4BP antibodies. The MFI value obtained from wt C4BP was set to 100% and used as a reference in comparison to the MFI values obtained for all other samples. Data are shown as means of three independent experiments ±SD. *, <i>p</i><0.01, compared to wt C4BP. B. Detection of bound C4BP and CCP deletions 7 and 8 with MK104. Same experiment as A using MK104, which is specific for CCP1 of C4BP. *, <i>p</i><0.01, compared to wt C4BP.</p

Rck is a C4BP binding protein.

<p>A, FACS analysis of C4BP binding. 2×10⁸ CFU/ml of BL21(DE3) and BL21(DE3) pRck in DPBS were mock treated (DPBS only) or incubated with 10% HIS for 30 min. C4BP binding was measured by FACS using a mouse monoclonal anti-human C4BP antibody. Mean fluorescence intensity (MFI) values are indicated. Representative data of an experiment performed at least three times are shown. B, Direct binding of ¹²⁵I-labeled C4BP to Rck. 1×10⁹ CFU/ml of BL21(DE3) and BL21(DE3) pRck in GVB were incubated with ¹²⁵I-C4BP (∼ 20,000 cpm/sample). The ratio of bound to total radioactivity was then determined (% bound). Data is expressed as means of two independent experiments performed in duplicate ± SD. C, Dose-dependent and saturable binding of C4BP to Rck. Bacteria prepared as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027546#pone-0027546-g001" target="_blank">Figure 1A</a> were incubated with increasing amounts of purified C4BP and detected by FACS as described above using a polyclonal anti-C4BP antiserum. Data is expressed as means of the MFI values acquired from three independent experiments ± SD.</p