Variation in the use of renal replacement therapy in patients with septic shock : a substudy of the prospective multicenter observational FINNAKI study

Peer reviewe

Chlamydia trachomatis Infection Induces Replication of Latent HHV-6

Peer reviewe

Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion.

Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis

Standard of hygiene and immune adaptation in newborn infants

Peer reviewe

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe

Antibody to Chlamydia trachomatis proteins, TroA and HtrA, as a biomarker for Chlamydia trachomatis infection

We studied whether antibody to two chlamydial proteins (TroA and HtrA) could be used as biomarkers of Chlamydia trachomatis infection. Methods: Recombinant proteins C. trachomatis TroA and HtrA were used as antigens in enzyme immunoassay (EIA). Both IgG and IgA antibody responses were studied. Results: IgG or IgA antibody to either protein was infrequently detected in sera from healthy blood donors or virgin girls. Patients attending the STI Clinic and patients with perihepatitis had often IgG antibody against TroA (25 and 50 % respectively) and HtrA (21 and 38 % respectively). Especially in sera from patients with chlamydial perihepatitis, the A(450nm) values with TroA were high (mean 1.591). A positive correlation between C. trachomatis MIF antibody and TroA (r = 0.7) as well as HtrA (r = 0.5) antibody was observed in sera from STI clinic patients and perihepatitis patients. Individuals with C. trachomatis infection and positive serology already when seeking medical attention had higher A(450nm) values for TroA (0.638) and HtrA (0.836) than patients with no marker of previous exposure or with no infection (0.208 and 0.234 respectively). Diagnosis of genital C. trachomatis infection is often NAAT-based, whereas serology has little value in testing for uncomplicated genital C. trachomatis infection. TroA and HtrA antibodies are potential biomarkers for evaluation of ascending and repeated C. trachomatis infection.Peer reviewe

Co-existence of HHV-6 and <i>Chlamydia</i> in cervical smears.

<p>Samples with detectable HHV-6 DNA as well as chlamydial (Ctr) DNA in cervical smears were grouped in this table. HHV-6 DNA load in cervical smears and in total blood from the respective samples are shown together with serological data for <i>Chlamydia</i> IgG, IgM and IgA. Ctr IgG values less than 32 (<32) indicate IgG negative. ND, not detected; POS, positive test result; NEG, negative test result.</p

Two-way Chi-square test to study the association between <i>Chlamydia</i> and HHV-6 load in cervical smear of all patients.

*<p>Samples have been arbitrarily divided into 4 sub groups (group 1, 2, 3 and 4) depending on the HHV-6 viral load. Respective HHV-6 DNA load is mentioned within brackets.</p>**<p>Similarly, all the samples have been arbitrarily divided into 3 sub groups (group A, B and C) depending on the chlamydial (Ctr) DNA load. Group A: more than 25,000 copies of Ctr/1000 cells, Group B: between 100–25,000 copies/1000 cells, Group C: Below 100 copies of Ctr (not detectable)/1000 cells.</p

Quantitative real time PCR assay to detect HHV-6 and chlamydial load in cervical swabs and total blood samples.

<p>(<b>A–C</b>) Standard curves for HHV-6 and <i>C. trachomatis</i> quantification. Ten fold serial dilutions of U94 HHV-6A (<b>A</b>), <i>C. trachomatis</i> (<b>B</b>) and PI15 (<b>C</b>) plasmids were tested in triplicates in qPCR reaction. Mean Ct values were plotted against the copy numbers. Correlation coefficients and slope values are mentioned in each figure. (<b>D</b>) Scatter plot showing quantitative distribution of HHV-6 and <i>C. trachomatis</i> in cervical swabs of patients (n = 65) with suspected <i>C. trachomatis</i> infection as determined by real-time qPCR assay. Samples with no detectable HHV-6 and <i>C. trachomatis</i> are not included. Samples with HHV-6 DNA below detection limit (5 copies/10³ cells) were arbitrarily specified as 4 copies/10³ cells. Similarly, samples with less than 100 copies/10³ cells were arbitrarily specified as 50 copies/10³ cells. Sensitivity of PCR was marked as detection limits.</p