Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence

Bladder incarceration following anterior external fixation of a traumatic pubic symphysis diastasis treated with immediate open reduction and internal fixation

Anterior pelvic ring disruptions are often associated with injuries to the genitourinary structures with the potential for considerable resultant morbidity. Herniation of the bladder into the symphyseal region after injury with subsequent entrapment upon reduction of the symphyseal diastasis has seldom been reported in the literature. We report such a case involving bladder herniation and subsequent entrapment after attempted closed reduction with anterior pelvic external fixation immediately treated with open reduction and internal fixation along with a review of the literature

Severity of Pain is not associated with Urgency of Diagnosis in ED Patients with Abdominal Pain

Background Abdominal Pain is the most common cause of visits to US Emergency Departments (EDs) and the causes range from urgent to non-urgent diagnoses. Distinguishing urgent versus non-urgent causes of abdominal pain is done through the use of clinical exam, lab studies and diagnostic imaging such as CT scans. There are no validated clinical decision rules to assist physicians in discriminating urgent from non-urgent causes of abdominal pain or which patient needs a CT scan. There is controversy regarding the use of CT scans for patients with abdominal pain due to the increased cost, radiation exposure and length of stay. Objective The objective of this study is to compare the demographics, pain score and CT utilization for patients with urgent versus non-urgent causes of abdominal pain. Methods At an academic ED, a convenience sample of patients with abdominal pain was prospectively enrolled by research assistants during the ED visit. Research assistants abstracted treatment information from the electronic medical record for the ED and hospitalization if applicable. Finally, enrollees were telephoned 2 weeks after the index ED visit to ascertain symptom resolution and treatment outcomes. Following establishment of final diagnosis, patients were classified as having an urgent or non-urgent diagnosis based upon published peer-reviewed criteria. Risk differences in pain severity, CT scan utilization and demographics were compared to urgency of diagnosis and a paired t-test was used to estimate differences in initial clinical characteristics. Results In a model of 725 patients, 144 had urgent diagnoses and 561 had non-urgent diagnoses. There was no distinction in insurance type, income level, mean age or pain score in the two groups. Ct scan utilization was higher in patients with urgent diagnoses (42.4% versus 16.4%.) Conclusion 20.4% of patients had an urgent diagnosis for the abdominal pain. There was no difference in the pain score for patients with urgent versus non-urgent diagnosis. While work-up bias is a potential limitation, CT scan utilization was higher in patients with an urgent diagnosis suggesting appropriate clinical judgement. Future studies will need to look at ways to target the testing to more high-risk patients who present with undifferentiated abdominal pain

Prospective biomarkers in preterm preeclampsia: A review

Preterm pre-eclampsia (prior to 37 weeks’ gestation) remains a major cause of maternal and fetal morbidity and mortality particularly in low to middle income countries. Much research has focused on first and second trimester predictors of pre-eclampsia with the aim of allowing stratification of antenatal care and trialling of potential preventative and therapeutic agents. However, none have been shown to be of benefit in randomised controlled trials. In this literature review we critically evaluate predictive and diagnostic tests for preterm pre-eclampsia and discuss their clinical use and potential value in the management of preterm pre-eclampsia. We defined preterm pre-eclampsia as pre-eclampsia occurring prior to 37 weeks’ gestation. Substantial progress has been made in the development of predictive screening tests for preterm pre-eclampsia, but further research is needed prior to their introduction and integration into routine clinical practice. The performance of diagnostic tests mainly utilising angiogenic and anti-angiogenic factors for determining time to delivery in later pregnancy currently hold more promise than first trimester predictive tests, possible reflecting the heterogeneity of pre-eclampsia

Placental Growth Factor: A review of literature and future applications

Placental growth factor is an angiogenic protein, highly expressed during pregnancy, which correlates well with placental function. In this review, we highlight the origin, structure and function of Placental Growth Factor and its receptors. We discuss how their pro-angiogenic/anti-angiogenic synergism is critical for successful placentation and how their imbalance may be utilised as a diagnostic marker of disease or a potential therapeutic target for adverse pregnancy outcomes

Hydrogel-forming microneedle arrays: Potential for use in minimally-invasive lithium monitoring

AbstractWe describe, for the first time, hydrogel-forming microneedle (s) (MN) arrays for minimally-invasive extraction and quantification of lithium in vitro and in vivo. MN arrays, prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) and crosslinked by poly(ethyleneglycol), imbibed interstitial fluid (ISF) upon skin insertion. Such MN were always removed intact. In vitro, mean detected lithium concentrations showed no significant difference following 30min MN application to excised neonatal porcine skin for lithium citrate concentrations of 0.9 and 2mmol/l. However, after 1h application, the mean lithium concentrations extracted were significantly different, being appropriately concentration-dependent. In vivo, rats were orally dosed with lithium citrate equivalent to 15mg/kg and 30mg/kg lithium carbonate, respectively. MN arrays were applied 1h after dosing and removed 1h later. The two groups, having received different doses, showed no significant difference between lithium concentrations in serum or MN. However, the higher dosed rats demonstrated a lithium concentration extracted from MN arrays equivalent to a mean increase of 22.5% compared to rats which received the lower dose. Hydrogel-forming MN clearly have potential as a minimally-invasive tool for lithium monitoring in outpatient settings. We will now focus on correlation between serum and MN lithium concentrations

Hobson’s choice? Constraints on accessing spaces of creative production

Successful creative production is often documented to occur in urban areas that are more likely to be diverse, a source of human capital and the site of dense interactions. These accounts chart how, historically, creative industries have clustered in areas where space was once cheap in the city centre fringe and inner city areas, often leading to the development of a creative milieu, and thereby stimulating further creative production. Historical accounts of the development of creative areas demonstrate the crucial role of accessible low-cost business premises. This article reports on the findings of a case study that investigated the location decisions of firms in selected creative industry sectors in Greater Manchester. The study found that, while creative activity remains highly concentrated in the city centre, creative space there is being squeezed and some creative production is decentralizing in order to access cheaper premises. The article argues that the location choices of creative industry firms are being constrained by the extensive city centre regeneration, with the most vulnerable firms, notably the smallest and youngest, facing a Hobson’s choice of being able to access low-cost premises only in the periphery. This disrupts the delicate balance needed to sustain production and begs the broader question as to how the creative economy fits into the existing urban fabric, alongside the competing demands placed on space within a transforming industrial conurbation

Surface Brightness Profiles of Composite Images of Compact Galaxies at z~4-6 in the HUDF

The Hubble Ultra Deep Field (HUDF) contains a significant number of B, V and i'-band dropout objects, many of which were recently confirmed to be young star-forming galaxies at z~4-6. These galaxies are too faint individually to accurately measure their radial surface brightness profiles. Their average light profiles are potentially of great interest, since they may contain clues to the time since the onset of significant galaxy assembly. We separately co-add V, i' and z'-band HUDF images of sets of z~4,5 and 6 objects, pre-selected to have nearly identical compact sizes and the roundest shapes. From these stacked images, we are able to study the averaged radial structure of these objects at much higher signal-to-noise ratio than possible for an individual faint object. Here we explore the reliability and usefulness of a stacking technique of compact objects at z~4-6 in the HUDF. Our results are: (1) image stacking provides reliable and reproducible average surface brightness profiles; (2) the shape of the average surface brightness profiles show that even the faintest z~4-6 objects are resolved; and (3) if late-type galaxies dominate the population of galaxies at z~4-6, as previous HST studies have shown, then limits to dynamical age estimates for these galaxies from their profile shapes are comparable with the SED ages obtained from the broadband colors. We also present accurate measurements of the sky-background in the HUDF and its associated 1-sigma uncertainties.Comment: 10 pages, 9 figures, 2 tables, emulateapj; Accepted for publication in The Astronomical Journa