Bacterial sRNAs play an important role in regulating many cellular processes including metabolism, outer membrane homeostasis and virulence. Although sRNAs were initially found in intergenic regions, there is emerging evidence that protein coding regions of the genome are a rich reservoir of sRNAs. Here we report that the 5΄UTR of IS200 transposase mRNA (tnpA) is processed to produce regulatory RNAs that affect expression of over 70 genes in Salmonella Typhimurium. We provide evidence that the tnpA derived sRNA base-pairs with invF mRNA to repress expression. As InvF is a transcriptional activator of SPI-1 encoded and other effector proteins, tnpA indirectly represses these genes. We show that deletion of IS200 elements in S. Typhimurium increases invasion in vitro and reduces growth rate, while over-expression of tnpA suppresses invasion. Our work indicates that tnpA acts as an sRNA ‘sponge’ that sets a threshold for activation of Salmonella pathogenicity island (SPI)-1 effector proteins and identifies a new class of ‘passenger gene’ for bacterial transposons, providing the first example of a bacterial transposon producing a regulatory RNA that controls host gene expression.

For a significant percentage of subjects, with chronic traumatic brain injury (TBI), who report persisting cognitive impairment and functional loss, the diagnosis is often impeded by the fact that routine neuroimaging often does not reveal any abnormalities. In this paper, we used diffusion tensor imaging (DTI) to investigate the apparently normal white matter (as assessed by routine magnetic resonance imaging) in the brains of 19 subjects with sub-acute (9) and chronic (10) TBI. We also assessed memory, executive function, and visual-motor coordination in these subjects. Using a voxel-wise approach, we investigated if parameters of diffusion were significantly different between TBI subjects and 17 healthy controls (HC), who were demographically matched to the TBI group. We also investigated if changes in DTI parameters were associated with neuropsychological performance in either group. Our results indicate significantly increased mean and axial diffusivity (MD and AD, respectively) values in widespread brain locations in TBI subjects, while controlling for age, sex, and time since injury. HC performed significantly better than the TBI subjects on tests of memory and executive function, indicating the persisting functional loss in chronic TBI. We found no correlation between diffusion parameters and performance on test of executive function in either group. We found negative correlation between FA and composite memory scores, and positive correlation between RD and visuomotor coordination test scores, in various tracts in both groups. Our study suggests that changes in MD and AD can indicate persisting micro-structure abnormalities in normal-appearing white matter in the brains of subjects with chronic TBI. Our results also suggest that FA in major white matter tracts is correlated with memory in health and in disease, alike; larger and longitudinal studies are needed to discern potential differences in these correlations in the two groups.

BackgroundEssential medicines lists and related policies are intended to meet the priority health needs of populations and their implementation is associated with more appropriate use of medicines. The World Health Organization (WHO) recommends that countries carefully select the medicines to be included in their national essential medicines lists. Lists that are used to prioritize access to important treatments should not include medicines that have been withdrawn elsewhere because of an unfavourable benefit-to-harm balance; however, countries still list and use medicines that have been withdrawn worldwide. The objective of this study was to determine whether the national essential medicines lists of 137 countries include medicines that have been withdrawn in other countries.Methods and findingsWe performed an audit of national essential medicines lists for medicines that had been withdrawn. Medicines withdrawn from worldwide markets between 1953 and 2014 were identified using a systematic review of published literature and regulatory documents. The reviewers used sources including the WHO’s database of drugs, PubMed, and the websites of regulatory agencies to obtain information regarding adverse effects associated with the medicines, the year of first withdrawal, markets of withdrawal, and the level of evidence supporting each withdrawal. We recorded the number of countries with a withdrawn medicine included in their national medicines list, the number of withdrawn medicines included in each nation’s list, and the number of national essential medicines including each withdrawn medicine. 97 medicines were withdrawn in at least one country but still included in one more national essential medicines list. Of 137 countries with a national essential medicines list, 136 lists included at least one withdrawn medicine, with 54% of the lists containing 5 or fewer withdrawn medicines, and 27% including 10 or more withdrawn medicines. 11 medicines were withdrawn worldwide but still included on at least one national essential medicines list. Countries with longer essential medicines lists had more withdrawn medicines included in their lists.ConclusionsThis study found that withdrawn medicines are included in all but one national essential medicines list, representing a need for more stringent processes for selecting and removing medicines on these lists. Countries may wish to apply special scrutiny to medicines withdrawn in other nations when selecting medicines to include on their lists.

ObjectivesThe Carefully Selected and Easily Accessible at No charge Medicines randomised controlled trial showed that patients receiving free access to medicines had improved diabetes and hypertension outcomes compared with patients who had usual access to medicines. In this study, we aimed to test the impact of providing free access to medicine to people with diabetes and hypertension on process of care indicators.DesignIn this post hoc analysis of randomised controlled trial findings, we identified process of care indicators for the management of diabetes and hypertension using relevant guidelines. The following process of care indicators were identified for diabetes management: encounters with healthcare professionals, blood pressure measurements, self-monitoring of blood glucose, annual eye and foot examination, annual administration of the influenza vaccine, and laboratory testing for glycated haemoglobin (HbA1c), low-density lipoprotein-cholesterol, serum creatinine and urine albumin to creatinine ratio. We identified the following process of care indicators for hypertension: encounters with healthcare professionals, blood pressure measurements, self-measuring of blood pressure, and serum tests for electrolytes, HbA1c, lipids and creatinine. Chart extractions were performed for all patients and the indicators for diabetes and hypertension were recorded. We compared the indicators for patients in each arm of the trial.ResultsThe study included 268 primary care patients. Free distribution of medicines may improve self-monitoring behaviours (adjusted rate ratio (aRR) 1.30; 95% CI 0.66 to 2.57) and reduce missed primary care appointments for patients with diabetes (aRR 0.80; 95% CI 0.48 to 1.33) or hypertension (aRR 0.41; 95% CI 0.18 to 0.90). Free distribution may also reduce primary care and consultant appointments and laboratory testing in patients with hypertension.ConclusionsImproving medicine accessibility for patients with diabetes and hypertension not only improves surrogate health outcomes but also improves the patient experience and may also reduce healthcare costs by encouraging self-monitoring.Trial registration numberThe randomised controlled trial mentioned is clinicaltrials.gov identifier: NCT02744963.