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We show that trimethoprim (TMP), an antibiotic in current use, displays a strong synergistic effect on mutagenesis in Escherichia coli when paired with the base analog 2-aminopurine (2AP), resulting in a 35-fold increase in mutation frequencies in the rpoB -Rif r system. Combination therapies are often employed both as antibiotic treatments and in cancer chemotherapy. However, mutagenic effects of these combinations are rarely examined. An analysis of the mutational spectra of TMP, 2AP, and their combination indicates that together they trigger a response via an alteration in deoxynucleoside triphosphate (dNTP) ratios that neither compound alone can trigger. A similar, although less strong, response is seen with the frameshift mutagen ICR191 and 2AP. These results underscore the need for testing the effects on mutagenesis of combinations of antibiotics and chemotherapeutics., (Copyright © 2019 American Society for Microbiology.)

We examined the mutagenic specificity of the widely used antibiotic ciprofloxacin (CPR), which displays weak to moderate mutagenic activity in several bacteria and generates short in-frame deletions in rpoB in Staphylococcus aureus To determine the spectrum of mutations in a system where any gene knockout would result in a recovered mutant, including frameshifts and both short and long deletions, we examined CPR-induced mutations in the thymidylate synthase-encoding thyA gene. Here, any mutation resulting in loss of thymidylate synthase activity generates trimethoprim (Trm) resistance. We found that deletions and insertions in all three reading frames predominated in the spectrum. They tend to be short deletions and cluster in two regions, one being a GC-rich region with potential extensive secondary structures. We also exploited the well-characterized rpoB-Rif(r) system in Escherichia coli to determine that cells grown in the presence of sublethal doses of CPR not only induced short in-frame deletions in rpoB, but also generated base substitution mutations resulting from induction of the SOS system. Some of the specific point mutations prominent in the spectrum of a strain that overproduces the dinB-encoded Pol IV were also present after growth in CPR. However, these mutations disappeared in CPR-treated dinB mutants, whereas the deletions remained. Moreover, CPR-induced deletions also occurred in a strain lacking all three SOS-induced polymerases. We discuss the implications of these findings for the consequences of overuse of CPR and other antibiotics., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Introduction: Spinal pain in the paediatric population is a significant health issue, with an increasing prevalence as they age. Paediatric patients attend for chiropractor care for spinal pain, yet, there is a paucity of quality evidence to guide the practitioner with respect to appropriate care planning., Methods: A retrospective chart review was used to describe chiropractic management of paediatric neck pain. Two researchers abstracted data from 50 clinical files that met inclusion criteria from a general practice chiropractic office in the Greater Toronto Area, Canada. Data were entered into SPSS 15 and descriptively analyzed., Results: Fifty paediatric neck pain patient files were analysed. Patients' age ranged between 6 and 18 years (mean 13 years). Most (98%) were diagnosed with Grade I-II mechanical neck pain. Treatment frequency averaged 5 visits over 19 days; with spinal manipulative therapy used in 96% of patients. Significant improvement was recorded in 96% of the files. No adverse events were documented., Conclusion: Paediatric mechanical neck pain appears to be successfully managed by chiropractic care. Spinal manipulative therapy appears to benefit paediatric mechanical neck pain resulting from day-today activities with no reported serious adverse events. Results can be used to inform clinical trials assessing effectiveness of manual therapy in managing paediatric mechanical neck pain.

Background: We compared the quality of structured abstracts of original research articles from the British Medical Journal (BMJ), Canadian Medical Association Journal (CMAJ), and the Journal of the American Medical Association (JAMA) from 1991 to 1992 and 2001 to 2002 between journals., Methods: A random, stratified sample of 54 abstracts from 2001 to 2002 in BMJ, CMAJ, and JAMA was compiled and coded. Two blinded raters reviewed 27 abstracts each against 33 objective criteria, separated into eight categories (purpose, research design, setting, subjects, intervention, measurement of variables, results, and conclusion). The quality score was the proportion of criteria present (range = 0-1)., Results: The overall mean quality score (0.74) for 2001-2002 was significantly higher than the 1988-1989 unstructured abstracts (mean = 0.57; p<0.001) but not different from the 1991-1992 structured abstracts (mean = 0.74; p>0.05). In 2001-2002, abstracts of CMAJ and JAMA (both means = 0.76) improved significantly over 1991-1992 (p<0.05) and scored significantly higher than BMJ (mean = 0.71; d.f. = 16, p<0.05). Some individual criteria scores (intervention, statistical information) improved but information was found consistently under-represented in areas that imply shortcomings of the studies., Interpretation: We found a consistency in abstract quality regardless of the precise format used by different journals. This indicates that the framework for research articles already in place should be maintained and further modification of the framework may not necessarily improve the abstract quality.