The importance of radiation quality for optimisation in radiology

Selection of the appropriate radiation quality is an important aspect of optimisation for every clinical imaging task in radiology, since it affects both image quality and patient dose. Spreadsheet calculations of attenuation and absorption have been applied to basic imaging tasks to provide an assessment of imaging performance for a selection of phosphors used in radiology systems. Contrast, which is an important component of image quality affected by radiation quality, has been assessed in terms of the contrast to noise ratio (CNR) for a variety of X-ray beams. Both CNR and patient dose fall with tube potential, and selection of the best option is a compromise that will provide an adequate level of image quality with as low a radiation dose as practicable. It is important that systems are set up to match the response of the imaging phosphor, as there are significant differences between phosphors. For example, the sensitivity of barium fluorohalides used in computed radiography declines at higher tube potentials, whereas that of gadolinium oxysulphide used in rare earth screens increases. Addition of 0.2 mm copper filters, which can reduce patient entrance surface dose by 50%, may be advantageous for many applications in radiography and fluoroscopy. The disadvantage of adding copper is that tube output levels have to be increased. Application of simple calculations of the type employed here could prove useful for investigating and assessing the implications of potential changes in X-ray beam quality prior to implementation of new techniques

Vagal sensory neurons drive mucous cell metaplasia

Summary: Airway sensory neuron-produced Substance P heightens allergy-induced goblet cell hyperplasia and hypersecretion of Muc5AC, electrically silencing these overreactive neurons reduced these components of lung type 2 allergic inflammatory response

Folding of small proteins: A matter of geometry?

We review some of our recent results obtained within the scope of simple lattice models and Monte Carlo simulations that illustrate the role of native geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic

GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents

Treating neuropathic pain is challenging and novel non-opioid based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence and in situ hybridization, we found the expression of the orphan GPCR (oGPCR) Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord (DH-SC) following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal (i.th.) CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights to its signaling pathways. CARTp is involved in many diseases including depression, reward and addiction, de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease

A role for core planar polarity proteins in cell contact-mediated orientation of planar cell division across the mammalian embryonic skin

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017. Supplementary information accompanies this paper at doi:10.1038/s41598-017-01971-2.The question of how cell division orientation is determined is fundamentally important for understanding tissue and organ shape in both healthy or disease conditions. Here we provide evidence for cell contact-dependent orientation of planar cell division in the mammalian embryonic skin. We propose a model where the core planar polarity proteins Celsr1 and Frizzled-6 (Fz6) communicate the long axis orientation of interphase basal cells to neighbouring basal mitoses so that they align their horizontal division plane along the same axis. The underlying mechanism requires a direct, cell surface, planar polarised cue, which we posit depends upon variant post-translational forms of Celsr1 protein coupled to Fz6. Our hypothesis has parallels with contact-mediated division orientation in early C. elegans embryos suggesting functional conservation between the adhesion-GPCRs Celsr1 and Latrophilin-1. We propose that linking planar cell division plane with interphase neighbour long axis geometry reinforces axial bias in skin spreading around the mouse embryo body.Peer reviewe

A multi-center study on the attitudes of Malaysian emergency health care staff towards allowing family presence during resuscitation of adult patients

BACKGROUND The practice of allowing family members to witness on-going active resuscitation has been gaining ground in many developed countries since it was first introduced in the early 1990s. In many Asian countries, the acceptability of this practice has not been well studied. AIM We conducted a multi-center questionnaire study to determine the attitudes of health care professionals in Malaysia towards family presence to witness ongoing medical procedures during resuscitation. METHODS Using a bilingual questionnaire (in Malay and English language), we asked our respondents about their attitudes towards allowing family presence (FP) as well as their actual experience of requests from families to be allowed to witness resuscitations. Multiple logistic regression was used to analyze the association between the many variables and a positive attitude towards FP. RESULTS Out of 300 health care professionals who received forms, 270 responded (a 90% response rate). Generally only 15.8% of our respondents agreed to allow relatives to witness resuscitations, although more than twice the number (38.5%) agreed that relatives do have a right to be around during resuscitation. Health care providers are significantly more likely to allow FP if the procedures are perceived as likely to be successful (e.g., intravenous cannulation and blood taking as compared to chest tube insertion). Doctors were more than twice as likely as paramedics to agree to FP (p-value = 0.002). This is probably due to the Malaysian work culture in our health care systems in which paramedics usually adopt a 'follow-the-leader' attitude in their daily practice. CONCLUSION The concept of allowing FP is not well accepted among our Malaysian health care providers

Dogs with separation-related problems show a “less pessimistic” cognitive bias during treatment with fluoxetine (Reconcile™) and a behaviour modification plan

Background Canine separation-related problems (SRP) (also described as “separation anxiety” or “separation distress”) are among the most common behavioural complaints of dog owners. Treatment with psychoactive medication in parallel with a behaviour modification plan is well documented in the literature, but it is unknown if this is associated with an improvement in underlying affective state (emotion and mood) or simply an inhibition of the behaviour. Cognitive judgement bias tasks have been proposed as a method for assessing underlying affective state and so we used this approach to identify if any change in clinical signs during treatment was associated with a consistent change in cognitive bias (affective state). Five dogs showing signs of SRP (vocalising – e.g. barking, howling-, destruction of property, and toileting – urination or defecation- when alone) were treated with fluoxetine chewable tablets (Reconcile™) and set on a standard behaviour modification plan for two months. Questionnaires and interviews of the owners were used to monitor the clinical progress of the dogs. Subjects were also evaluated using a spatial cognitive bias test to infer changes in underlying affect prior to, and during, treatment. Concurrently, seven other dogs without signs of SRP were tested in the same way to act as controls. Furthermore, possible correlations between cognitive bias and clinical measures were also assessed for dogs with SRP. Results Prior to treatment, the dogs with SRP responded to ambiguous positions in the cognitive bias test negatively (i.e. with slower running speeds) compared to control dogs (p < 0.05). On weeks 2 and 6 of treatment, SRP dogs displayed similar responses in the cognitive bias test to control dogs, consistent with the possible normalization of affect during treatment, with this effect more pronounced at week 6 (p > 0.05). Questionnaire based clinical measures were significantly correlated among themselves and with performance in the cognitive bias test. Conclusion These results demonstrate for the first time that the clinical treatment of a negative affective state and associated behaviours in a non-human species can produce a shift in cognitive bias. These findings demonstrate how the outcome of an intervention on a clinical problem can be evaluated to determine not only that the subject’s behaviour has improved, but also its psychological state (welfare

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

Isolation of microplastics in biota-rich seawater samples and marine organisms.

notes: PMCID: PMC3970126types: Journal Article; Research Support, Non-U.S. Gov'tThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Microplastic litter is a pervasive pollutant present in aquatic systems across the globe. A range of marine organisms have the capacity to ingest microplastics, resulting in adverse health effects. Developing methods to accurately quantify microplastics in productive marine waters, and those internalized by marine organisms, is of growing importance. Here we investigate the efficacy of using acid, alkaline and enzymatic digestion techniques in mineralizing biological material from marine surface trawls to reveal any microplastics present. Our optimized enzymatic protocol can digest >97% (by weight) of the material present in plankton-rich seawater samples without destroying any microplastic debris present. In applying the method to replicate marine samples from the western English Channel, we identified 0.27 microplastics m(-3). The protocol was further used to extract microplastics ingested by marine zooplankton under laboratory conditions. Our findings illustrate that enzymatic digestion can aid the detection of microplastic debris within seawater samples and marine biota.Natural Environment Research Council (NERC