Antimicrobial resistance in human populations: challenges and opportunities.

Antimicrobial resistance (AMR) is a global public health threat. Emergence of AMR occurs naturally, but can also be selected for by antimicrobial exposure in clinical and veterinary medicine. Despite growing worldwide attention to AMR, there are substantial limitations in our understanding of the burden, distribution and determinants of AMR at the population level. We highlight the importance of population-based approaches to assess the association between antimicrobial use and AMR in humans and animals. Such approaches are needed to improve our understanding of the development and spread of AMR in order to inform strategies for the prevention, detection and management of AMR, and to support the sustainable use of antimicrobials in healthcare

Office Chit-Chat as a Social Ritual: The Uplifting Yet Distracting Effects of Daily Small Talk at Work

This is the author accepted manuscript. The final version is available from the Academy of Management via the DOI in this recordSmall talk—short, superficial, or trivial communication not core to task completion—is normative and ubiquitous in organizations. Although small talk comprises one-third of adults’ speech, its effects at work have been discounted. Integrating theories of interaction rituals and micro-role transitions, we explore how and why seemingly inconsequential conversations during the workday generate meaningful effects on employees’ experiences. In a sample of employed adults from a Northeast US University’s alumni database and LinkedIn (n = 151), we used an experience sampling method (ESM) to capture within-individual variation in small talk over three weeks. We also conducted a validation of our daily small talk measure with Masters students from a Northeastern US University (n = 73) and two samples of employed adults registered with Amazon Turk (n = 180 and n = 202). Results showed that, on one hand, small talk enhanced employees’ daily positive social emotions at work, which translated into heightened organizational citizenship behaviors (OCB) and well-being at the end of the workday; on the other hand, small talk disrupted employees’ ability to cognitively engage in their work, which compromised their OCB. Our results also showed higher levels of trait-level self-monitoring mitigated the negative effects of small talk on work engagement. Combined, results suggest that the polite, ritualistic, and formulaic nature of small talk is often uplifting yet distracting

Erratum: Antimicrobial resistance in human populations: challenges and opportunities - ERRATUM.

[This corrects the article DOI: 10.1017/gheg.2017.4.]

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Microvascular function is preserved in newly diagnosed rheumatoid arthritis and low systemic inflammatory activity

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease and may be affected in RA. It is, however, presently unknown at what point in the disease course the abnormalities in microvascular function occur. We determined whether microvascular function is already disturbed in early disease-modifying antirheumatic drugs (DMARD)-naive RA patients with low systemic inflammation. Fifteen consecutive RA patients with a median symptom duration of 5 months, a C-reactive protein level of ≤20 mg/l and without a history of cardiovascular disease, and age 15 and sex-matched healthy controls were recruited. Endothelium-dependent and endothelium-independent vasodilatation in skin was evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. CRP and ESR levels were mildly, but significantly elevated in patients compared to controls. No differences in both endothelium-dependent vasodilatation and capillary recruitment were observed between groups [709% (95% CI, 457–961%) vs 797% (95% CI, 556–1,037%), P = 0.59 and 37% (95% CI, 26–47%) vs 41% (95% CI, 31–50%), P = 0.59, respectively]. Skin microvascular function is preserved in early, DMARD-naive RA patients with moderately active RA but low systemic inflammatory activity. Both the extent of the systemic inflammation and disease duration, therefore, may be important determinants of microvascular dysfunction and subsequent increased risk for cardiovascular disease

A Systems Approach to Improving Rural Care in Ethiopia

Background: Multiple interventions have been launched to improve the quality, access, and utilization of primary health care in rural, low-income settings; however, the success of these interventions varies substantially, even within single studies where the measured impact of interventions differs across sites, centers, and regions. Accordingly, we sought to examine the variation in impact of a health systems strengthening intervention and understand factors that might explain the variation in impact across primary health care units. Methodology/Principal Findings: We conducted a mixed methods positive deviance study of 20 Primary Health Care Units (PHCUs) in rural Ethiopia. Using longitudinal data from the Ethiopia Millennium Rural Initiative (EMRI), we identified PHCUs with consistently higher performance (n = 2), most improved performance (n = 3), or consistently lower performance (n = 2) in the provision of antenatal care, HIV testing in antenatal care, and skilled birth attendance rates. Using data from site visits and in-depth interviews (n = 51), we applied the constant comparative method of qualitative data analysis to identify key themes that distinguished PHCUs with different performance trajectories. Key themes that distinguished PHCUs were 1) managerial problem solving capacity, 2) relationship with the woreda (district) health office, and 3) community engagement. In higher performing PHCUs and those with the greatest improvement after the EMRI intervention, health center and health post staff were more able to solve day-to-day problems, staff had better relationships with the woreda health official, an

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

SnTox3 Acts in Effector Triggered Susceptibility to Induce Disease on Wheat Carrying the Snn3 Gene

The necrotrophic fungus Stagonospora nodorum produces multiple proteinaceous host-selective toxins (HSTs) which act in effector triggered susceptibility. Here, we report the molecular cloning and functional characterization of the SnTox3-encoding gene, designated SnTox3, as well as the initial characterization of the SnTox3 protein. SnTox3 is a 693 bp intron-free gene with little obvious homology to other known genes. The predicted immature SnTox3 protein is 25.8 kDa in size. A 20 amino acid signal sequence as well as a possible pro sequence are predicted. Six cysteine residues are predicted to form disulfide bonds and are shown to be important for SnTox3 activity. Using heterologous expression in Pichia pastoris and transformation into an avirulent S. nodorum isolate, we show that SnTox3 encodes the SnTox3 protein and that SnTox3 interacts with the wheat susceptibility gene Snn3. In addition, the avirulent S. nodorum isolate transformed with SnTox3 was virulent on host lines expressing the Snn3 gene. SnTox3-disrupted mutants were deficient in the production of SnTox3 and avirulent on the Snn3 differential wheat line BG220. An analysis of genetic diversity revealed that SnTox3 is present in 60.1% of a worldwide collection of 923 isolates and occurs as eleven nucleotide haplotypes resulting in four amino acid haplotypes. The cloning of SnTox3 provides a fundamental tool for the investigation of the S. nodorum–wheat interaction, as well as vital information for the general characterization of necrotroph–plant interactions

A knowledge-driven GIS modeling technique for groundwater potential mapping at the Upper Langat Basin, Malaysia.

The aim of this paper is to use a knowledge-driven expert-based geographical information system (GIS) model coupling with remote-sensing-derived parameters for groundwater potential mapping in an area of the Upper Langat Basin, Malaysia. In this study, nine groundwater storage controlling parameters that affect groundwater occurrences are derived from remotely sensed imagery, available maps, and associated databases. Those parameters are: lithology, slope, lineament, land use, soil, rainfall, drainage density, elevation, and geomorphology. Then the parameter layers were integrated and modeled using a knowledge-driven GIS of weighted linear combination. The weightage and score for each parameter and their classes are based on the Malaysian groundwater expert opinion survey. The predicted groundwater potential map was classified into four distinct zones based on the classification scheme designed by Department of Minerals and Geoscience Malaysia (JMG). The results showed that about 17% of the study area falls under low-potential zone, with 66% on moderate-potential zone, 15% with high-potential zone, and only 0.45% falls under very-high-potential zone. The results obtained in this study were validated with the groundwater borehole wells data compiled by the JMG and showed 76% of prediction accuracy. In addition statistical analysis indicated that hard rock dominant of the study area is controlled by secondary porosity such as distance from lineament and density of lineament. There are high correlations between area percentage of predicted groundwater potential zones and groundwater well yield. Results obtained from this study can be useful for future planning of groundwater exploration, planning and development by related agencies in Malaysia which provide a rapid method and reduce cost as well as less time consuming. The results may be also transferable to other areas of similar hydrological characteristics