Low frequency of septic arthritis after arthrocentesis and intra-articular glucocorticoid injection.

Objective: The aim of this study was to evaluate the risk of septic arthritis (SA) in patients who received an intra-articular (IA) glucocorticoid (GC) injection and to describe the characteristics of these patients. Methods: All patients undergoing IA procedures at the orthopaedic and rheumatological departments on the Danish island of Funen from January 2006 to December 2013 were identified in the central database and included by register extraction. Patients who developed a clinically inflamed joint and positive synovial fluid culture within 14 days after IA GC injection were considered as having SA. Retrospectively, data on age, gender, affected joint location, bacterial agent, pre-existing inflammatory disorder, and death within 30 days were extracted from the patient files. According to local recommendations, a non-touch sterile technique was used for IA procedures. Patients were informed about the risk of SA and advised to seek medical attention on suspicion of infection or lack of improvement. Results: In total, 22 370 IA procedures were performed. Among these, 14 118 GC injections and 8252 arthrocenteses were undertaken. Only 11 patients were diagnosed with SA (0.08%, 95% confidence interval 0.03-0.12). Risk factors for SA were male gender, age, and pre-existing joint disease. Conclusion: We found a low frequency of SA subsequent to IA GC injections. Older patients with pre-existing joint disease are at higher risk of developing SA.

Added Value from Secondary Use of Person Generated Health Data in Consumer Health Informatics.

Introduction: Various health-related data, subsequently called Person Generated Health Data (PGHD), is being collected by patients or presumably healthy individuals as well as about them as much as they become available as measurable properties in their work, home, and other environments. Despite that such data was originally just collected and used for dedicated predefined purposes, more recently it is regarded as untapped resources that call for secondary use. Method: Since the secondary use of PGHD is still at its early evolving stage, we have chosen, in this paper, to produce an outline of best practices, as opposed to a systematic review. To this end, we identified key directions of secondary use and invited protagonists of each of these directions to present their takes on the primary and secondary use of PGHD in their sub-fields. We then put secondary use in a wider perspective of overarching themes such as privacy, interpretability, interoperability, utility, and ethics. Results: We present the primary and secondary use of PGHD in four focus areas: (1) making sense of PGHD in augmented Shared Care Plans for care coordination across multiple conditions; (2) making sense of PGHD from patient-held sensors to inform cancer care; (3) fitting situational use of PGHD to evaluate personal informatics tools in adaptive concurrent trials; (4) making sense of environment risk exposure data in an integrated context with clinical and omics-data for biomedical research. Discussion: Fast technological progress in all the four focus areas calls for a societal debate and decision-making process on a multitude of challenges: how emerging or foreseeable results transform privacy; how new data modalities can be interpreted in light of clinical data and vice versa; how the sheer mass and partially abstract mathematical properties of the achieved insights can be interpreted to a broad public and can consequently facilitate the development of patient-centered services; and how the remaining risks and uncertainties can be evaluated against new benefits. This paper is an initial summary of the status quo of the challenges and proposals that address these issues. The opportunities and barriers identified can serve as action items individuals can bring to their organizations when facing challenges to add value from the secondary use of patient-generated health data.

A missense mutation in the rpoC gene affects chromosomal replication control in Escherichia coli.

An RNA polymerase mutant with a single-base-pair change in the rpoC gene affects chromosome initiation control. The mutation, which is recessive, is a G to A transition leading to the substitution of aspartate for glycine at amino acid residue 1033 in the RNA polymerase beta' subunit. The chromosome copy number is increased twofold in the mutant at semipermissive growth temperatures (39 degrees C). In a delta oriC strain, in which chromosome initiation is governed by an F replicon, chromosome copy number is not affected. Plasmid pBR322 copy number is also increased in the mutant at 39 degrees C. The mutation causes a more than fivefold increased expression of the dnaA gene at 39 degrees C. It is conceivable that it is this high DnaA concentration which causes the high chromosome copy number and that the mutant RNA polymerase beta' subunit exerts its effect by altering the expression of the dnaA gene. However, other factors must be affected as well to explain why the RNA polymerase mutant can grow in a balanced fashion with a high chromosome concentration. This is in contrast to wild-type cells, which exhibit higher origin concentrations when DnaA protein is overproduced, but in which the overall DNA concentration is only moderately affected.

Characterization of toxin from different strains of Pasteurella multocida serotype A and D.

Chromosomal DNA from 13 different selected Pasteurella multocida spp. multocida strains of serotypes A and D were isolated and compared. All 10 toxigenic strains were recognized by a DNA probe which included the toxA gene coding for the Pasteurella multocida toxin (PMT). None of the three nontoxigenic strains reacted with the DNA probe. Toxin from the 10 toxigenic strains were isolated and compared. All were found to possess the biological characteristics previously described for the PMT isolated from P. multocida ssp. multocida NCTC 12178, including molecular mass of approx. 143 kDa and reactivity with a series of monoclonal antibodies. Toxin prepared from different toxigenic strains could not be differentiated immunologically by tandem crossed immunoelectrophoresis, Toxin, which was affinity purified from four of the strains and subsequently inactivated by formaldehyde, was cross-protective when used for vaccination of mice before challenge with PMT. It is concluded that the toxin from toxigenic strains of P. multocida ssp. multocida must be very similar, if not identical.

Vaccination against progressive atrophic rhinitis with a recombinant Pasteurella multocida toxin derivative.

Vaccination against progressive atrophic rhinitis using a purified recombinant derivative of the Pasteurella multocida toxin (PMT), was carried out. Ten pregnant gilts were vaccinated twice with the nontoxic derivative (dO) which apart from a lack of 121 amino acids had an amino acid sequence identical to PMT, while seven gilts were vaccinated with a purified, formaldehyde treated, native PMT and ten gilts served as non-vaccinated controls. The resulting piglets were inoculated intranasally with Bordetella bronchiseptica and toxigenic P. multocida. Among piglets from the nonvaccinated gilts all except one developed clinical atrophic rhinitis and 90% developed severe turbinate atrophy while only a few pigs in the vaccinated groups developed clinical or pathological signs of disease. Gilt colostra from the two vaccinated groups had similar mean anti-PMT titers and the mean titers in the offspring's sera from these groups were nearly identical throughout the study. No pigs born from unvaccinated gilts were seropositive until 8 wk of age (7 wk post-challenge) but 23% became seropositive at slaughter. The infection rate with toxigenic P. multocida in piglets and the total number of P. multocida colonies cultured from nasal swabs were significantly reduced at 5 wk and 8 wk of age in the vaccinated groups, when compared to controls. There was a significantly improved weight gain (greater than 9%) from birth to slaughter in offspring from vaccinated gilts. No significant differences in feed conversion rate or % lean meat were observed among the groups. The study showed the excellent immunoprotective properties of the nontoxic derivative of the PMT molecule.

Recombinant derivatives of Pasteurella multocida toxin: candidates for a vaccine against progressive atrophic rhinitis.

Potential vaccine components for protection against atrophic rhinitis in pigs were developed. This was achieved by deletion mutagenesis of the gene encoding the Pasteurella multocida toxin. Four purified toxin derivatives lacking different and widely separated regions in the amino acid sequence were characterized by a lack of toxic activity. One such component was shown to induce efficient protection of vaccinated female mice and their offspring against challenge with purified P. multocida toxin.

The complete nucleotide sequence of the Pasteurella multocida toxin gene and evidence for a transcriptional repressor, TxaR.

The osteolytic toxin of Pasteurella multocida induces bone resorption in vivo and in vitro (Foged et al., 1988; Kimman et al., 1987). In this report the toxin-encoding toxA gene is sequenced, and the deduced primary structure of the toxin shows a protein of 1285 amino acids, containing a striking homology to a metal-binding motif. Evidence that expression of the toxA gene is repressed at a transcriptional level in Escherichia coli is presented. Repression could be abolished either by deletion of a region upstream of toxA, or by a putative frame-shift mutation in the same region. The repressor protein encoded within this region was efficient in trans, and was named TxaR.

Cloning and expression of the Pasteurella multocida toxin gene, toxA, in Escherichia coli.

A chromosomal DNA library of a toxigenic type D strain of Pasteurella multocida subsp. multocida was established in Escherichia coli. From this library two clones, SPE308 and SPE312, were identified by using a monoclonal antibody against the osteoclast-stimulating P. multocida toxin (PMT). Extracts of these clones showed cytopathic activity identical to that of extracts of toxigenic P. multocida. The recombinant plasmids, pSPE308 and pSPE312, directed the synthesis of a protein with an apparent molecular weight of 143,000 which could be specifically detected by anti-PMT antibody. The recombinant toxin, which was located in the cytoplasm of E. coli, was purified by affinity chromatography with immobilized monoclonal antibody and was shown to react in a manner identical to that of PMT in a quantitative structural test using a series of monoclonal antibodies as well as in all quantitative functional tests used, i.e., tests for dermonecrotic activity and mouse lethality and the embryonic bovine lung cell test for cytopathic activity. The gene encoding this toxic activity was named toxA and was found to be present in the chromosome of toxigenic strains only of P. multocida. A probe spanning the toxA gene therefore has potential in the diagnosis and surveillance of progressive atrophic rhinitis in pigs.