A multicenter, prospective, randomized comparison of a novel signal transmission capsule endoscope to an existing capsule endoscope.

BACKGROUND: MiroCam, a capsule endoscope, uses a novel transmission technology, electric-field propagation, which uses the human body as a conduction medium for data transmission. OBJECTIVE: To compare the ability of the MiroCam (MC) and PillCam (PC) to identify sources of obscure GI bleeding (OGIB). DESIGN: Prospective, multicenter, comparative study. SETTING: Six academic hospitals. PATIENTS: A total of 105 patients with OGIB. INTERVENTION: Patients ingested both the MC and PC capsules sequentially in a randomized fashion. MAIN OUTCOME MEASUREMENTS: Concordance of rates in identifying a source of OGIB, operational times, and rates of complete small-bowel examination. RESULTS: Data analysis resulted in 43 (48%) abnormal cases identifying a source of OGIB by either capsule. Twenty-four cases (55.8%) were positive by both capsules. There was negative agreement in 46 of 58 cases (79.3%). The κ index was 0.547 (χ(2) = 1.32; P = .36). In 12 cases, MC positively identified a source that was not seen on PC, whereas in 7 cases, PC positively identified a source that was not seen on MC. MC had a 5.6% higher rate of detecting small-bowel lesions (P = .54). MC captured images at 3 frames per second for 11.1 hours, and PC captured images at 2 frames per second for 7.8 hours (P \u3c .0001). Complete small-bowel examination was achieved in 93.3% for MC and 84.3% for PC (P = .10). LIMITATIONS: Readers were not blinded to the particular capsule they were reading. CONCLUSION: A positive diagnostic finding for OGIB was identified by either capsule in 48% of cases. The concordance rate between the 2 capsules was comparable to that of prior studies in identifying sources of small-bowel bleeding. The longer operational time of the MC may result in higher rates of complete small-bowel examination, which may, in turn, translate into a higher rate of detecting small-bowel lesions. (Clinical trial registration number: NCT00878982.)

GEO-6 assessment for the pan-European region

Through this assessment, the authors and the United Nations Environment Programme (UNEP) secretariat are providing an objective evaluation and analysis of the pan-European environment designed to support environmental decision-making at multiple scales. In this assessment, the judgement of experts is applied to existing knowledge to provide scientifically credible answers to policy-relevant questions. These questions include, but are not limited to the following:• What is happening to the environment in the pan-European region and why?• What are the consequences for the environment and the human population in the pan-European region?• What is being done and how effective is it?• What are the prospects for the environment in the future?• What actions could be taken to achieve a more sustainable future?<br/

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The mode of action and role of cGMP-mediated gene transcription in macrophages

Background: Nitric oxide (NO) and carbon monoxide (CO) gaseous signalling molecules are important factors in the pathogenesis of inflammatory disease as they regulate leukocyte activation, platelet aggregation and vasodilation. Cyclic-3’-5’guanosine monophosphate (cGMP) is a second messenger for NO, CO and several other mediators and pharmaceutical agents. cGMP has many well-described effects mediated by post-translational modifications, such as inhibition of vascular smooth muscle contraction. Its analogue, cyclic-3’-5’-adenosine monophosphate (cAMP) is well-known to modulate gene expression via the transcription factor cAMP-response element binding protein (CREB). In contrast, the gene regulatory effects of cGMP were until now essentially unknown. Hypothesis: cGMP regulates gene expression in macrophages via a CREB-dependent pathway. Methods and Results: Experiments were carried out on human blood-derived macrophages (HMDMs) from normal donors. In these, cGMP cell permeable analogue, dibutyryl-cGMP (dbcGMP), induced well-known CREB-target genes, such as NR4A2 and FOS. This effect was replicated with the co-treatment of CO-releasing molecule 3 (CORM3) and phosphodiesterase5 inhibitor, sildenafil but not with the treatment of NO-donors S-nitroso-Nacetylpenicillamine (SNAP) and sodium nitroprusside. dbcGMP, SNAP and CORM3 with sildenafil induced activating phosphorylation of CREB. Additionally, dbcGMP treatment induced the direct binding of CREB to the NR4A2 enhancer, as measured by ChIP-qPCR. dbcGMP-induced NR4A2 expression was attenuated by siRNAmediated CREB knockdown. Next, CREB gene was deleted in human monocytic U937 cell line via CRISPR/Cas9 technology. NR4A2 was induced by dbcGMP stimulation in control, but not in CREB-deficient U937 cells. RNA-sequencing of HMDMs revealed 59 genes regulated by dbcGMP only, 184 genes regulated by dbcAMP only and 114 genes regulated by both. The effect of dbcAMP and dbcGMP on gene expression were closely related, with both gene sets positively correlating with each other (p<0.05), as measured by gene set enrichment analysis. In contrast, dbcGMP and dbcAMP gene sets negatively correlated with an in vivo human inflammatory gene set (p<0.05). RNA-Sequencing revealed important gene targets not previously known to be cGMP-regulated that may mediate downstream functions such as NR1D1, CCR2, TLR5 and HSPA1. Conclusion: This data defines cGMP-mediated gene regulation, an almost completely novel area, and characterises CREB as a predominant mediating transcription factor in human macrophages. This adds significant insights to both inflammation biology and gene regulation.Open Acces

Guillemot Press

Guillemot Press is an award-winning publishing company founded by Luke Thompson in 2016. By 2021 we will have published approximately 50 titles featuring some of the most exciting poets writing in English today, from experimental debut writers to international prize-winners. The press is thematically defined, rather than formally or stylistically, and has a special focus on the materiality of book-making, using a range of print techniques, including letterpress, litho and digital, and a range of binding and paper stock choices. We won the Michael Marks Publishers Award for this work in December 2018 and our books have won awards for their design and illustration. As well as publishing books, Guillemot Press has a website that includes features and interviews. We have curated numerous exhibitions and readings, from Penzance to the Shetlands, taking in Bristol, London, Liverpool, Edinburgh, Orkney, and many other locations across the UK, and we co-curate the Bodmin Moor Poetry Festival

Non-typhoidal salmonellosis presenting as acute calculus cholecystitis

Non-typhoidal Salmonella spp.are Gram-negative bacilli, which typically cause a clinical picture of gastroenteritis and, less commonly, patients may become a chronic carrier of the pathogen within their gallbladder. We describe a rare clinical presentation of a non-typhoidal Salmonella spp. infection as acute calculus cholecystitis in an adult patient. Salmonella enterica subsp. Salamae (ST P4271) was grown from cholecystostomy fluid, and the patient subsequently underwent a laparoscopic cholecystectomy that demonstrated a necrotic gallbladder fundus. We advise that microbiological sampling of bile is essential, especially in the context of foreign travel, to detect unusual pathogens as in this case or common pathogens that may have unusual antimicrobial resistance. Given the necrotic gallbladder as in this case, we also advise that early cholecystectomy should be strongly considered in these patients.</jats:p

Search efficiency for multiple targets

In most visual search experiments, there is only one possible target object or class of objects. The experiment reported here compares performance in these single-target searches against performance when the target can be either of two different stimuli. The targets used in this experiment were color squares. Results showed that conducting two single-target searches is more efficient than carrying out a dual target search. If visual search is driven by a mental template of the object to be found, then searches for two targets may require a very general template, or a pair of templates that are active simultaneously, which apparently produces less efficient search. Many real world search tasks, such as searches of X-ray images by baggage screeners, require simultaneous search for very different targets (“Find any guns or knives or explosive devices.”). This need for generality could result in search that is less directed and therefore less efficient

Costs in searching for two targets: dividing search across target types could improve airport security screening

The cost of searching for two visual targets simultaneously was compared against two separate single-target searches using exposure time and accuracy measures within a staircase procedure. Dual-target search for all stimuli (colour, shape and orientation) exhibited a loss of accuracy for one target. For orientation and shape, this dual-target cost in accuracy was extreme, with chance-level performance on one target. For colour, dual-target search exhibited an additional cost in search time, with search requiring a longer exposure than the summed time required for two single-target searches. An additional search-time cost was also found for orientation targets when irrelevant colour variation was added to the display. In conclusion, dual-target search for dissimilar targets is accompanied by an accuracy cost. Furthermore, colour variation, whether task-relevant or not, leads to an additional cost in processing speed. The results suggest that a divided-effort strategy would improve performance in search tasks such as X-ray baggage screening

Peripheral blood mononuclear cell gene expression and cytokine profiling in patients with intermittent claudication who exhibit exercise induced acute renal injury

Background Intermittent claudication (IC) is a common manifestation of peripheral arterial disease. Some patients with IC experience a rise in Urinary N-acetyl-β-D-Glucosaminidase (NAG)/ Creatinine (Cr) ratio, a marker of renal injury, following exercise. In this study, we aim to investigate whether peripheral blood mononuclear cells (PBMC) from patients with IC who exhibit a rise in urinary NAG/ Cr ratio following exercise exhibit differential IL-10/ IL-12 ratio and gene expression compared to those who do not have a rise in NAG/ Cr ratio. Methods We conducted a single center observational cohort study of patients diagnosed with IC. Blood and urine samples were collected at rest and following a standardised treadmill exercise protocol. For comparative analysis patients were separated into those with any rise in NAG/Cr ratio (Group 1) and those with no rise in NAG/Cr ratio (Group 2) post exercise. Isolated PBMC from pre- and post-exercise blood samples were analysed using flow cytometry. PBMC were also cultured for 20 hours to perform further analysis of IL-10 and IL-12 cytokine levels. RNA-sequencing analysis was performed to identify differentially expressed genes between the groups. Results 20 patients were recruited (Group 1, n = 8; Group 2, n = 12). We observed a significantly higher IL-10/IL-12 ratio in cell supernatant from participants in Group 1, as compared to Group 2, on exercise at 20 hours incubation; 47.24 (IQR 9.70–65.83) vs 6.13 (4.88–12.24), p = 0.04. 328 genes were significantly differentially expressed between Group 1 and 2. The modulated genes had signatures encompassing hypoxia, metabolic adaptation to starvation, inflammatory activation, renal protection, and oxidative stress. Discussion Our results suggest that some patients with IC have an altered immune status making them ‘vulnerable’ to systemic inflammation and renal injury following exercise. We have identified a panel of genes which are differentially expressed in this group of patients. </jats:sec