A critical survey of some attempts to define 'computer', beginning with some informal ones (from reference books, and definitions due to H. Simon, A.L. Samuel, and M. Davis), then critically evaluating those of three philosophers (J.R. Searle, P.J. Hayes, and G. Piccinini), and concluding with an examination of whether the brain and the universe are computers.
A common metaphor used to describe heterosexual relationships frames men as predators and women as prey. The present work assessed potential consequences of these metaphoric portrayals. Participants read a heterosexual dating scenario that did or did not metaphorically frame the situation in predator and prey terms. Using a U.S. college undergraduate sample of 120 women and 82 men in Study 1, exposure to these metaphors led to greater rape myth acceptance among men (but not among women). Using a broader sample of 76 women and 72 men via MTurk, Study 2 replicated these results and also found metaphor exposure led to greater rape myth acceptance and rape proclivity. Furthermore, a mediation analysis indicated that men exposed to these metaphors were more likely to accept rape myths, which in turn predicted their self-reported greater rape proclivity. Such results demonstrate the harmful outcomes that can result from describing romantic interactions where men are the predators and women are the prey.
Acta Neurologica Scandinavica, EarlyView.
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Cancer Medicine, EarlyView.
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X chromosome gain has been previously described in male breast cancer (MBC). Androgen receptor (AR) gene is located on X chromosome. The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.
The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia. Cases were tested by fluorescence in situ hybridization (FISH) to assess the X chromosome status and AR amplification. AR expression was studied by immunohistochemistry (IHC). In addition, AR methylation status was assessed.
X chromosome gain was observed in 74.7% of invasive duct carcinoma, in 20.6% of in situ duct carcinoma, and in 14.6% of gynecomastia when associated with cancer, while all cases of tumor-free gynecomastia showed wild X chromosome asset. AR gene copy number when increased paralleled the number of X chromosomes. AR IHC expression was observed in 100% of MBC tested. AR gene methylation status revealed low level or absence of methylation.
These data suggest that X chromosome can play a role in the neoplastic transformation of male breast epithelium. X chromosome gain is paralleled by AR gene polysomy. Polysomic AR genes show low methylation levels and high AR protein expression on IHC. These data should be taken into consideration for MBC treatment planning.
International Journal for Numerical Methods in Biomedical Engineering, EarlyView.
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Single-molecule pull-down (SiMPull) can capture native protein complexes directly from cell lysates for analysis of complex composition and activities at the single-molecule level. Although SiMPull requires many fewer cells compared to conventional pull-down assays, all studies so far have been performed using lysates from many cells. In principle, extending SiMPull to the single-cell level will allow the investigation of cell-to-cell variations on the stoichiometry and activities of biomolecular complexes.
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The aim was to determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active psoriatic arthritis (PsA) who are tumour necrosis factor inhibitor (TNFi) naïve and without concomitant moderate-to-severe psoriasis, and who have responded inadequately to conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs).
The study took the perspective and setting of the UK National Health Service (NHS).
The model structure was a 3-month decision tree leading into a Markov model. Separate analyses based on the number of prior csDMARDs (one and two or more) were conducted, with secukinumab 150 mg compared to standard of care (SoC) and TNFis, respectively, for each subpopulation. Clinical parameters, including response at 3 months, were from the FUTURE 2 trial and a network meta-analysis. Outcomes included total costs and quality-adjusted life years (QALYs) over the 40-year time horizon (3.5% annual discount for both outcomes; cost year 2017), and incremental cost effectiveness ratios (ICERs).
The ICER for secukinumab 150 mg versus SoC was £28,748 per QALY gained (one prior csDMARD). Secukinumab 150 mg dominated golimumab, certolizumab pegol and etanercept, and had an ICER of £5680 per QALY gained versus adalimumab and > £1 million saved per QALY foregone versus infliximab (two or more prior csDMARDs). Valuing one QALY at between £20,000 and £30,000, the probability of secukinumab having the highest net monetary benefit was 48.9% (one prior csDMARD) and 88.9% (two or more prior csDMARDs). Parameters related to Health Assessment Questionnaire scores were most influential.
Secukinumab 150 mg at list price appears to represent a cost-effective use of NHS resources for adults with PsA who have responded inadequately to one or two or more prior csDMARDs.
Publication date: Available online 24 May 2018
Source:Women and Birth
Author(s): Elizabeth C. Rigg, Virginia Schmied, Kath Peters, Hannah G. Dahlen
BackgroundIn Australia, the provision of homebirth services by unregulated birthworkers (doulas, ex-registered midwives, traditional midwives and lay workers) has increased. Accessing a homebirth with a registered midwife via mainstream services is limited. Concern is growing that new legislation aimed at prohibiting unregulated birthworkers practice may result in homebirth going underground.AimTo explore the role, practice and training of unregulated birthworkers in Australian and establish what they would do if legislation prohibited their practice.MethodsThis study used a mixed methods sequential exploratory design to explore the practice, training and role of unregulated birthworkers in Australia. In phase one, four unregulated birthworkers were interviewed in-depth and the findings informed the development of a survey in phase two. This was distributed nationally through two consumer websites, social media, Facebook and email. Data from both phases were integrated.FindingsUnregulated birthworkers in Australia provide homebirth services to women with high and low-risk pregnancies when this choice is unavailable or unacceptable within mainstream services. They operate covertly to protect their practice and avoid the scrutiny of authorities. Unregulated birthworkers can be experienced and trained in childbirth care and practice, much like a midwife working within a holistic paradigm of care.ConclusionUnregulated birthworkers believe they provide women with the homebirth service they want but cannot access. Mainstream service providers need to listen to consumer criticisms, as women seek answers outside the system. Change is needed to improve and align services with women's expectations of homebirth.
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In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. Additionally, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathological roles of mutated tau.
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Cristina Mauri | Guangxia Wang | Stefan Schulte-Merker
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ANZ Journal of Surgery, EarlyView.
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ANZ Journal of Surgery, EarlyView.
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USPSTF now recommends men under age 70 discuss pros and cons with a physician.
Mutation is one of the most fundamental evolutionary forces. Studying variation in the mutation rate within and among closely-related species can help reveal mechanisms of genome divergence, but such variation is unstudied in the vast majority of organisms. Previous studies on ciliated protozoa have found extremely low mutation rates. In this study, using mutation-accumulation techniques combined with deep whole-genome sequencing, we explore the germline base-substitution mutation-rate variation of three cryptic species in the Paramecium aurelia species complex-P. biaurelia, P. sexaurelia, and P. tetraurelia. We find that there is extremely limited variation of the mutation rate and spectrum in the three species and confirm the extremely low mutation rate of ciliates.
Genomic data for the closest relatives of house mice (Mus musculus species complex) are surprisingly limited. Here, we present the first complete genome for a behaviorally and ecologically unique member of the sister clade to house mice, the mound-building mouse, Mus spicilegus. Using read cloud sequencing and de novo assembly we produced a 2.50 Gbp genome with a scaffold N50 of 2.27 Mbp. We constructed >25 000 gene models, of which the majority had high homology to other Mus species. To evaluate the utility of the M. spicilegus genome for behavioral and ecological genomics, we extracted 196 vomeronasal receptor (VR) sequences from our genome and analyzed phylogenetic relationships between M. spicilegus VRs and orthologs from M. musculus and the Algerian mouse, M. spretus. While most M. spicilegus VRs clustered with orthologs in M. musculus and M. spretus, 10 VRs with evidence of rapid divergence in M. spicilegus are strong candidate modulators of species-specific chemical communication. A high quality assembly and genome for M. spicilegus will help to resolve discordant ancestry patterns in house mouse genomes, and will provide an essential foundation for genetic dissection of phenotypes that distinguish commensal from non-commensal species, and the social and ecological characteristics that make M. spicilegus unique.
The pyruvate dehydrogenase complex (PDH), that converts pyruvate to acetyl-coA, is regulated by pyruvate dehydrogenase kinases (PDHK) and phosphatases (PDHP) that have been shown to be important for morphology, pathogenicity and carbon source utilisation in different fungal species. The aim of this study was to investigate the role played by the three PDHKs PkpA, PkpB and PkpC in carbon source utilisation in the reference filamentous fungus Aspergillus nidulans, in order to unravel regulatory mechanisms which could prove useful for fungal biotechnological and biomedical applications. PkpA and PkpB were shown to be mitochondrial whereas PkpC localised to the mitochondria in a carbon source-dependent manner. Only PkpA was shown to regulate PDH activity. In the presence of glucose, deletion of pkpA and pkpC resulted in reduced glucose utilisation, which affected carbon catabolite repression (CCR) and hydrolytic enzyme secretion, due to de-regulated glycolysis and TCA cycle enzyme activities. Furthermore, PkpC was shown to be required for the correct metabolic utilisation of cellulose and acetate. PkpC negatively regulated the activity of the glyoxylate cycle enzyme isocitrate lyase (ICL), required for acetate metabolism. In summary, this study identified PDHKs important for the regulation of central carbon metabolism in the presence of different carbon sources, with effects on the secretion of biotechnologically important enzymes and carbon source-related growth. This work demonstrates how central carbon metabolism can affect a variety of fungal traits and lays a basis for further investigation into these characteristics with potential interest for different applications.
Background: Pearl millet is a non-model grain and fodder crop adapted to extremely hot and dry environments globally. In India, a great deal of public and private sectors' investment has focused on developing pearl millet single cross hybrids based on the cytoplasmic-genetic male sterility (CMS) system, while in Africa most pearl millet production relies on open pollinated varieties. Pearl millet lines were phenotyped for both the inbred parents and hybrids stage. Many breeding efforts focus on phenotypic selection of inbred parents to generate improved parental lines and hybrids. This study evaluated two genotyping techniques and four genomic selection schemes in pearl millet. Results: Despite the fact that 6x more sequencing data were generated per sample for RAD-seq than for tGBS, tGBS yielded more than 2x as many informative SNPs (defined as those having MAF > 0.05) than RAD-seq. A genomic prediction scheme utilizing only data from hybrids generated prediction accuracies (median) ranging from 0.73-0.74 (1000-grain weight), 0.87-0.89 (days to flowering time), 0.48-0.51 (grain yield) and 0.72-0.73 (plant height). For traits with little to no heterosis, hybrid only and hybrid/inbred prediction schemes performed almost equivalently. For traits with significant mid-parent heterosis, the direct inclusion of phenotypic data from inbred lines significantly (p<0.05) reduced prediction accuracy when all lines were analyzed together. However, when inbreds and hybrid trait values were both scored relative to the mean trait values for the respective populations, the inclusion of inbred phenotypic datasets moderately improved genomic predictions of the hybrid genomic estimated breeding values. Conclusion: Here we show that modern approaches to genotyping by sequencing can enable genomic selection in pearl millet. While historical pearl millet breeding records include a wealth of phenotypic data from inbred lines, we demonstrate that the naive incorporation of this data into a hybrid breeding program can reduce prediction accuracy, while controlling for the effects of heterosis per se allowed inbred genotype and trait data to improve the accuracy of genomic estimated breeding values for pearl millet hybrids.
Potato (Solanum tuberosum) is a staple food crop and is considered one of the main sources of carbohydrates worldwide. Late blight (Phytophthora infestans) and common scab (Streptomyces scabies) are two of the primary production constraints faced by potato farming. Previous studies have identified a few resistance genes for both late blight and common scab; however, these genes explain only a limited fraction of the heritability of these diseases. Genomic selection has been demonstrated to be an effective methodology for breeding value prediction in many major crops (e.g., maize and wheat). However, the technology has received little attention in potato breeding. We present the first genomic selection study involving late blight and common scab in tetraploid potato. Our data involves 4,110 Single Nucleotide Polymorphisms (SNPs) genetic markers and field evaluations for 1,763 late blight phenotypes collected in seven years and 3,885 common scab phenotypes in nine years. We report moderately high genomic heritability estimates (0.46±0.04 and 0.45±0.017, for late blight and common scab, respectively). The extent of genotype-by-year interaction was high for late blight and low for common scab. Our assessment of prediction accuracy demonstrates the applicability of genomic prediction for tetraploid potato breeding. For both traits, we found that more than 90% of the genetic variance could be captured with an additive model. For common scab, the highest prediction accuracy was achieved using an additive model. For late blight, small but statistically significant gains in prediction accuracy were achieved using a model that accounted for both additive and dominance effects. Using whole-genome regression models we identified SNPs located in previously reported hotspots regions for late blight, on genes associated with systemic disease resistance responses, and a new locus located in a WRKY transcription factor for common scab.
To determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active ankylosing spondylitis (AS) who have not responded adequately to previous treatment with conventional care (CC; biologic-naïve population) or previous biologic therapy (biologic-experienced population).
UK National Health Service (NHS).
The model was structured as a 3-month decision tree leading into a Markov model. Comparators were licensed tumour necrosis factor inhibitors (including available biosimilars) and CC in the biologic-naïve and biologic-experienced populations, respectively. Clinical parameters captured treatment response, short-term disease activity and patient functioning, as well as long-term structural disease progression. Utilities were derived from secukinumab trial data. List prices were used for all drugs. The cost year was 2017 and costs and outcomes were discounted at 3.5%.
In the biologic-naïve population, secukinumab dominated adalimumab and certolizumab pegol. Incremental cost-effectiveness ratios (ICERs) versus other comparators were either below £10,000 per quality-adjusted life-year (QALY) gained or south-west ICERs that implied cost effectiveness of secukinumab. In biologic-experienced patients, the ICER for secukinumab versus CC was £4927 per QALY gained. Treatment response rates, short-term treatment effects, long-term radiographic progression and biologic acquisition costs were key model drivers. Scenario analysis found results to be robust to changes in model structural assumptions. Probabilistic analysis identified greater uncertainty in results in the biologic-naïve population.
Even at list price, secukinumab appears to represent a cost-effective use of NHS resources for biologic-naïve and biologic-experienced patients with active AS. Further research on long-term radiographic progression outcomes would be valuable for future cost-effectiveness analyses in AS.
Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for manipulability and tolerance of transgenes. Poor tumour-selectivity, off-target sequestration and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumour selective virotherapy targeted to αvβ6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but non-detectable in healthy tissues. Experimental Design: Ad5NULL-A20 harbours mutations in each major capsid protein to preclude uptake via all native pathways. Tumour-tropism via αvβ6-targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed. Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5NULL-A20 via coxsackie and adenovirus receptor (CAR), αvβ3/5 integrins and coagulation factor 10 (FX). Ad5NULL-A20 efficiently and selectively transduced αvβ6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of pre-existing anti-Ad5 immunity. In vivo biodistribution of Ad5NULL-A20 following systemic delivery in non-tumour-bearing mice was significantly reduced in all off-target organs, including a remarkable 107-fold reduced genome accumulation in the liver compared to Ad5. Tumour uptake, transgene expression and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5NULL-A20-treated animals demonstrated significantly improved survival compared to those treated with oncolytic Ad5.
Conclusions: Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-over-expressing cancers, and exciting platforms for tumour selective over-expression of therapeutic anti-cancer modalities, including immune checkpoint inhibitors.
The strategy of using biologically-targeted therapeutics for cancer has yet to translate into effective treatment of gliomas. The neuro-oncology community is beginning to recognize that phase 0 studies should be performed to account for the impact of the blood-brain-barrier on the ability of a therapeutic to reach its target(s).
Purpose: The tumor microenvironment presents with altered extracellular matrix (ECM) and stroma composition which may affect treatment efficacy and contribute to tissue stiffness. Ultrasound (US) elastography can visualize and quantify tissue stiffness non-invasively. However, the contributions of ECM and stroma components to stiffness are poorly understood. We therefore set out to quantify ECM and stroma density and their relation to tumor stiffness. Experimental Design: A modified clinical ultrasound system was used to measure tumor stiffness and perfusion during tumor growth in pre-clinical tumor models. In vivo measurements were compared with collagen mass spectroscopy and automatic analysis of matrix and stroma markers derived from immunofluorescence images. Results: US elastography estimates of tumor stiffness were positively correlated with tumor volume in collagen and myofibroblast-rich tumors, while no correlations were found for tumors with low collagen and myofibroblast content. US elastography measurements were strongly correlated with ex vivo mechanical testing and mass spectroscopy-based measurements of total collagen and immature collagen crosslinks. Registration of ultrasound and confocal microscopy data showed strong correlations between blood vessel density and T-cell density in syngeneic tumors, while no correlations were found for genetic tumor models. In contrast to collagen density, which was positively correlated with stiffness, no significant correlations were observed for hyaluronic acid density. Finally, localized delivery of collagenase led to a significant reduction in tumor stiffness without changes in perfusion 24 hours after treatment. Conclusions: US elastography can be used as a potential biomarker to assess changes in the tumor microenvironment, particularly changes affecting the ECM.
THURSDAY, May 24, 2018 -- A hyperactive and asymmetric velocity-storage mechanism may be responsible for intermittent attacks of vertigo in some patients with recurrent spontaneous vertigo (RSV) of unknown etiology, according to a study published...
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THURSDAY, May 24, 2018 -- Further research is needed on the use of platelet-rich therapy for facial aesthetics and alopecia, according to a review published in the May issue of Plastic and Reconstructive Surgery. Catherine C. Motosko, from New York...
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THURSDAY, May 24, 2018 -- Patients served by the beleaguered Veterans Affairs health system may have wider access to private care, thanks to a bill approved Wednesday by the Senate. President Donald Trump is known to support the bill, which now...
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THURSDAY, May 24, 2018 -- Parents are advised to choose the injectable flu vaccine for the 2018 to 2019 season, according to a decision published by the American Academy of Pediatrics (AAP), which will publish a formal policy statement on the issue...
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THURSDAY, May 24, 2018 -- An ingestible micro-bio-electronic device (IMBED) could be used for in situ biomolecular detection based on environmentally resilient biosensor bacteria and luminescence readout electronics, according to a study published...
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Developments in imaging techniques over the past two decades have enhanced the diagnosis and evaluation of muscle disorders. Two of the most commonly used imaging modalities, magnetic resonance imaging (MRI) and ultrasound (US), have received increasing attention in both clinical neuromuscular clinical care and research (Mercuri et al., 2007; Pillen et al., 2008). MRI has shown versatility due to its ability to assist in disease diagnosis, as a biomarker of disease progression, and as a tool to assess metabolic alterations (Kuo and Carrino, 2007; Andreassen et al., 2009; Ekstrand et al., 2012).
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In the localization of wireless agents, ambiguous measurements have significant implications regarding the complexity and quality of the agents' positioning. Ambiguous measurements occur, for example, in multiple...
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We report the first case of composite lymphoma consisting of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL) and high-grade B-cell lymphoma with MYC and BCL2 rearrangem...
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Radiotherapy is one of the most common and effective treatment methods for cancer, and improving the radiosensitivity of tumor tissues during the treatment process is vital. We report the mechanisms of glycoge...
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Extended prostate needle core biopsies are standard of care for the diagnosis of prostatic carcinoma. Subsequent biopsies may be performed for a variety of indications. Knowledge of biopsy characteristics indicating risk for progression may have utility to guide therapeutic management. Prostate needle core biopsies performed between 2008–2014 were reviewed. Patients with at least 1 subsequent biopsy were identified. Cases were categorized by worst initial diagnosis. Gleason ≤6 carcinoma was further classified as significant or insignificant with insignificant defined as: ≤2 cores with carcinoma, sites with ≤50% carcinoma, and unilateral carcinoma.
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Magnetic seizure therapy (MST) is currently under research as an alternative treatment approach to electroconvulsive therapy (ECT) in treatment-resistant depression (TRD). Compared to ECT́s electrical stimulation, MST uses strong magnetic stimulation for seizure induction under anesthesia. MST is associated with a reduced passage of induced current through specific brain regions probably included in cognitive side effects by ECT (Deng et al., 2011). Currently, the optimal stimulation parameters of MST to induce seizure are far away from clinical routine.
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The gums can turn pale for several reasons. Pale gums around the teeth may indicate anemia, which is often caused by a lack of iron, folate, or vitamin B12. If the gums are painful and the paleness is patchy or web-like, the cause may be more severe. Here, learn about underlying conditions and when to see a doctor.
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Cancer Cytopathology, EarlyView.
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The publishers and authors of this issue of Hematology/Oncology Clinics of North America wish to express our collective gratitude to our editor, Dr. Colin Sieff. Despite perilous distractions he has conceived, organized, edited and shepherded all of our efforts into an issue of which we can be very proud. We all wish the Sieff family good health and well-deserved happiness.
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Pernicious anaemia (PA) is associated with increased gastric cancer risk, but the evidence is conflicting regarding the associated risk of other cancers.
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Endoscopists who encounter an interval colorectal cancer (I-CRC) may be concerned about the implications because I-CRCs may represent a lapse in colonoscopy quality and a missed opportunity for prevention. To determine the I-CRC rate per colonoscopy examination and to examine the effect of colonoscopy volume and adenoma detection rate (ADR) on the number of I-CRCs attributable to an endoscopist.
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This study compares how throughput and output factors affect emergency department (ED) median waiting room time.
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Cancer, EarlyView.
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FAM188B enhances cell survival via interaction with USP7
FAM188B enhances cell survival via interaction with USP7, Published online: 24 May 2018; doi:10.1038/s41419-018-0650-6
FAM188B enhances cell survival via interaction with USP7HDAC and Ku70 axis- an effective target for apoptosis induction by a new 2-cyano-3-oxo-1,9-dien glycyrrhetinic acid analogue
HDAC and Ku70 axis- an effective target for apoptosis induction by a new 2-cyano-3-oxo-1,9-dien glycyrrhetinic acid analogue, Published online: 24 May 2018; doi:10.1038/s41419-018-0602-1
HDAC and Ku70 axis- an effective target for apoptosis induction by a new 2-cyano-3-oxo-1,9-dien glycyrrhetinic acid analogueClinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1β-induced autophagy
Clinical isolates of the modern <i>Mycobacterium tuberculosis</i> lineage 4 evade host defense in human macrophages through eluding IL-1β-induced autophagy, Published online: 24 May 2018; doi:10.1038/s41419-018-0640-8
Clinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1β-induced autophagyGamma synuclein is a novel Twist1 target that promotes TGF-β-induced cancer cell migration and invasion
Gamma synuclein is a novel Twist1 target that promotes TGF-β-induced cancer cell migration and invasion, Published online: 24 May 2018; doi:10.1038/s41419-018-0657-z
Gamma synuclein is a novel Twist1 target that promotes TGF-β-induced cancer cell migration and invasionHBx-induced S100A9 in NF-κB dependent manner promotes growth and metastasis of hepatocellular carcinoma cells
HBx-induced S100A9 in NF-κB dependent manner promotes growth and metastasis of hepatocellular carcinoma cells, Published online: 24 May 2018; doi:10.1038/s41419-018-0512-2
HBx-induced S100A9 in NF-κB dependent manner promotes growth and metastasis of hepatocellular carcinoma cellsCorrection to: Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice
Correction to: Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice, Published online: 24 May 2018; doi:10.1038/s41419-018-0639-1
Correction to: Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in miceMicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signaling
MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signaling, Published online: 24 May 2018; doi:10.1038/s41419-018-0690-y
MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence, and angiogenic signalingREGγ deficiency suppresses tumor progression via stabilizing CK1ε in renal cell carcinoma
REGγ deficiency suppresses tumor progression via stabilizing CK1ε in renal cell carcinoma, Published online: 24 May 2018; doi:10.1038/s41419-018-0646-2
REGγ deficiency suppresses tumor progression via stabilizing CK1ε in renal cell carcinomaTo describe admission pattern and outcome with its predictor variable on the mortality of children admitted to pediatric intensive care unit (PICU), Ayder Referral Hospital, Northern Ethiopia, from September 2...
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This randomized controlled trial evaluates the effects of two different rest periods between as set of balance exercises after stroke during inpatient rehabilitation.
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EMS industry members demonstrated what it means to be "Stronger Together" by motivating each other through social media
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From memorial statues to challenge coins, first responders are feeling the love from states around the country
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T-lymphocytes are involved in tumor progression and regression. Actinic keratoses (AK) are atypical proliferations of keratinocytes of the skin. Some AK progress into invasive cutaneous squamous cell carcinomas (cSCC). Keratoacanthomas (KA) are either classified as a cSCC subtype or a benign tumor with histologic resemblance to well-differentiated cSCC as it is supposed to regress spontaneously. In contrast, cSCC represent malignant tumors that may metastasize.
To compare the T-lymphocyte profiles of AK, KA and cSCC in relation to PD-L1 expression.
Tissue micro-arrays of 103 cases of AK, 43 cases of KA and 106 cases of cSCC were stained by immunohistochemistry for E-cadherin, CD3, CD4, CD8, FOXp3, and the receptor–ligand pair PD-1/PD-L1. Immunohistological scores were computationally determined to assess PD-L1 expression as well as the expression profiles of T-lymphocytes.
AK had lower numbers of CD3+ and PD-1+ cells compared to KA and lower numbers of CD3+, CD8+ and PD-1+ cells in comparison with cSCC. KA showed significantly higher numbers of CD4+ and FOXp3+ cells as well as lower numbers of CD8+ cells in comparison with invasive cSCC. cSCC expressed significantly more PD-L1 in comparison with AK and KA. Among cSCC PD-L1 expression was higher in moderately and poorly-differentiated cSCC than in well-differentiated cSCC. Increased PD-L1 expression also correlated with increased numbers of CD4+, CD8+ and FOXp3+ cells in cSCC.
Tumor-associated T-lymphocyte infiltrates showed significant differences between AK, KA and invasive cSCC. PD-L1 expression correlated with invasion of T-cell infiltrates in invasive cSCC.
THURSDAY, May 24, 2018 -- Active major depression (MD) in the male partner may lower the likelihood of pregnancy, according to a study published in the May issue of Fertility & Sterility. Emily A. Evans-Hoeker, M.D., from Virginia Tech Carilion...
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THURSDAY, May 24, 2018 -- South Asians in the United States have increased proportional mortality rates from atherosclerotic cardiovascular disease (ASCVD), although there are no unique risk factors in this population, according to a scientific...
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THURSDAY, May 24, 2018 -- For children with X-linked hypophosphatemia, subcutaneous burosumab is associated with decreases in rickets severity and with improved renal tubular phosphate reabsorption, according to a study published in the May 24 issue...
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THURSDAY, May 24, 2018 -- Prostate-specific antigen (PSA) levels three months after radiotherapy (RT) are strong markers of prostate cancer outcomes for patients with intermediate- and high-risk disease, according to a study published online May 4...
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THURSDAY, May 24, 2018 -- Each hour of delay in detecting abnormal lactates in patients with sepsis increases the odds of in-hospital death, according to a study published online May 24 in CHEST. Xuan Han, M.D., from the University of Chicago, and...
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THURSDAY, May 24, 2018 -- Financial incentives added to free cessation aids can improve the rate of sustained abstinence among smokers, according to a study published online May 23 in the New England Journal of Medicine. Scott D. Halpern, M.D.,...
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THURSDAY, May 24, 2018 -- There is considerable global variation in personal health care access and quality, according to a study published online May 23 in The Lancet. Nancy Fullman, M.P.H., from the Institute for Health Metrics and Evaluation, and...
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THURSDAY, May 24, 2018 -- Greater perceived social isolation is associated with an increased risk of death and health care use among patients with heart failure, according to a study published online May 23 in the Journal of the American Heart...
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THURSDAY, May 24, 2018 -- Regional anesthesia is associated with a lower opioid consumption in both knee and hip replacement surgeries, compared to general anesthesia, according to a study published May 14 in PAIN Practice. Katharina Donauer, M.D.,...
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THURSDAY, May 24, 2018 -- For non-Hispanic whites, rising fatal drug overdose rates are associated with increases in the mortality rate and years of potential life lost from 1999 to 2015, according to a study published online May 22 in the American...
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This protocol describes the use of a body composition analyzer and metabolic animal monitoring system to characterize body composition and metabolic parameters in mice. An obesity model induced by high-fat feeding is used as an example for the application of these techniques.
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Here, we present protocols to visualize calcium (Ca2+) responses elicited by HeLa cells infected by Shigella. By optimizing the parameters of bacterial infection and imaging with Ca2+ fluorescent probes, atypical global and local Ca2+ signals induced by bacteria over a large range of infection kinetics are characterized.
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Fluorescent protein-based approaches to monitor effectors secreted by bacteria into host cells are challenging. This is due to the incompatibility between fluorescent proteins and the type-III secretion system. Here, an optimized split superfolder GFP system is used for visualization of effectors secreted by bacteria into the host plant cell.
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T-lymphocytes are involved in tumor progression and regression. Actinic keratoses (AK) are atypical proliferations of keratinocytes of the skin. Some AK progress into invasive cutaneous squamous cell carcinomas (cSCC). Keratoacanthomas (KA) are either classified as a cSCC subtype or a benign tumor with histologic resemblance to well-differentiated cSCC as it is supposed to regress spontaneously. In contrast, cSCC represent malignant tumors that may metastasize.
To compare the T-lymphocyte profiles of AK, KA and cSCC in relation to PD-L1 expression.
Tissue micro-arrays of 103 cases of AK, 43 cases of KA and 106 cases of cSCC were stained by immunohistochemistry for E-cadherin, CD3, CD4, CD8, FOXp3, and the receptor–ligand pair PD-1/PD-L1. Immunohistological scores were computationally determined to assess PD-L1 expression as well as the expression profiles of T-lymphocytes.
AK had lower numbers of CD3+ and PD-1+ cells compared to KA and lower numbers of CD3+, CD8+ and PD-1+ cells in comparison with cSCC. KA showed significantly higher numbers of CD4+ and FOXp3+ cells as well as lower numbers of CD8+ cells in comparison with invasive cSCC. cSCC expressed significantly more PD-L1 in comparison with AK and KA. Among cSCC PD-L1 expression was higher in moderately and poorly-differentiated cSCC than in well-differentiated cSCC. Increased PD-L1 expression also correlated with increased numbers of CD4+, CD8+ and FOXp3+ cells in cSCC.
Tumor-associated T-lymphocyte infiltrates showed significant differences between AK, KA and invasive cSCC. PD-L1 expression correlated with invasion of T-cell infiltrates in invasive cSCC.
EMS1 leaders reflect on the fitting theme of EMS Week 2018, and how their colleagues have furthered their own careers and contributions to the field
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AbstractObjectives
Patients with diabetes are at high risk for polypharmacy (ie, use of multiple medications) for treatment of diabetes, associated comorbidities and other coexisting conditions. This study aims to estimate the prevalence of polypharmacy and factors associated with polypharmacy among adult patients with diabetes.
MethodsA cross-sectional retrospective observational study of adults with diabetes, who visited the outpatient clinic of a tertiary teaching hospital in Saudi Arabia, was conducted. Data were extracted from the Electronic Health Record database for a period of 12 months (January–December 2016). Polypharmacy was defined as the cumulative use of five or more medications. Polypharmacy among adults with diabetes was measured by calculating the average number of medications prescribed per patient. A multivariable logistic regression model was used to examine the factors associated with polypharmacy.
ResultsA total of 8932 adults with diabetes were included in this study. Of these, nearly 78% had polypharmacy which was more likely among women as compared with men and more likely among older adults (age ≥60 years) as compared with the adults. Also, polypharmacy was two times as likely among patients with coexisting cardiovascular conditions (adjusted OR (AOR)=2.89; 95% CI 2.54 to 3.29), respiratory disease (AOR=2.42; 95% CI 1.92 to 3.03) and mental health conditions (AOR=2.19; 95% CI 1.74 to 2.76), and three times as likely among patients with coexisting musculoskeletal disease (AOR=3.16; 95% CI 2.31 to 4.30) as compared with those without these coexisting chronic conditions categories.
ConclusionsPolypharmacy is common among patients with diabetes, with an even higher rate in older adults patients. Healthcare providers can help in detecting polypharmacy and in providing recommendations for simplifying medication regimens and minimising medications to enhance the outcome of diabetes care.
Objectives
The study aims to compare the risk of chronic kidney diseases (CKDs) between patients with schizophrenia using first and second-generation antipsychotics.
SettingDatasets of 2000–2013 National Health Insurance in Taiwan were used.
ParticipantsThe National Health Insurance reimbursement claims data have been transferred to and managed by the National Health Research Institute in Taiwan since 1996. We used the Psychiatric Inpatient Medical Claims database, a subset of the National Health Insurance Research Database, comprising a cohort of patients hospitalised for psychiatric disorders between 2000 and 2013 (n=2 67 807). The database included patients with at least one psychiatric inpatient record and one discharge diagnosis of mental disorders coded by the International Classification of Diseases, Ninth Revision (ICD-9) codes 290–319. The age of patients at first admission was restricted to 18–65 years.
Primary outcomeCKD (ICD-9 code 582, 583, 585, 586, 588) requiring hospitalisation or three outpatient visits. The diagnosis of CKD follows the criteria of 'Kidney Disease: Improving Global Outcomes' in Taiwan. CKD is defined as a kidney damage as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens or glomerular filtration rate <60 mL/min/1.73 m2 for 3 months or more.
ResultsWe found that the risks for CKD were higher for those who used second-generation antipsychotics (SGAs) longer cumulatively than those who did not. Using non-users, patients did not have any SGA records, as reference group, the risks for CKD comparing those using SGAs for 90 to 180 days with non-users and those using SGAs for more than 1000 days were 1.42 (1.06–1.91) and 1.30 (1.13–1.51), respectively.
ConclusionsThe current study suggests the relationship between using SGAs and risk of CKD.
Introduction
Stroke is the second most common cause of death after ischaemic heart diseases and the third leading cause of disability worldwide. The contribution of cardiac complications to the mortality of patients with stroke is variable across studies, ranging from 12.5% to 22.7%. Many of these cardiac complications are preventable, and early recognition and adequate management guided by appropriate up-to-date knowledge of their relative incidence and fatality can help to improve patients' outcomes. This systematic review aims to summarise the available data on the burden of cardiac complications after stroke.
Methods and analysisThis review will include all cross-sectional, case–control and cohort studies and clinical trials published between 1 January 1950 and 31 December 2017, involving adults and/or children, and reporting on the prevalence, the incidence and/or the mortality of cardiac complications after stroke. Two reviewers will independently screen titles and abstracts of records retrieved from PubMed, Excerpta Medica Database, ISI Web of Science and the Cumulative Index to Nursing and Allied Health Literature for eligibility, and then assess the risk of bias and quality of reporting to select the studies which will be included. All authors will contribute to the retrieval of full texts of eligible records and data extraction. Heterogeneity across studies will be evaluated by the 2 test on Cochran's Q statistic. Study-specific estimates of the prevalence, incidence and mortality of cardiac complications after stroke across studies will be pooled through random-effect or fixed-effect meta-analysis depending on the source of the heterogeneity, after stabilising the variance of individual studies using the Freeman-Tukey double arcsine transformation. Visual analysis of funnel plots and Egger's test will be done to detect small-study effect.
Ethics and disseminationThis review and meta-analysis will be based on published data and will therefore not require a specific ethical clearance. The results will be published in peer-reviewed journals.
PROSPERO registration numberCRD42018082551.
Objective
To assess the efficacy of gelatine tannate (a complex of tannic acid with astringent and anti-inflammatory properties, and a protective gelatine) for the treatment of acute gastroenteritis (AGE) in children.
DesignRandomised, double-blind, placebo-controlled trial. Intention-to-treat analysis.
SettingTwo paediatric hospitals in Warsaw.
ParticipantsChildren younger than 5 years of age with AGE, defined as a change in stool consistency to a loose or liquid form (according to the Bristol Stool Form Scale or Amsterdam Stool Form Scale) and/or an increase in the frequency of evacuations (≥3 in 24 hours), lasting for no longer than 5 days.
InterventionsSeventy-two children were assigned to receive gelatine tannate (n=36) or placebo (n=36) in addition to standard rehydration therapy. The gelatine tannate was administered at an age-dependent dose (250–500 mg), and both study products were taken four times per day for 5 days.
Primary and secondary outcome measuresThe main outcome measure was duration of diarrhoea. Secondary outcomes included the need for intravenous rehydration, need for hospitalisation of outpatients, number of watery stools per day, vomiting, weight gain, adverse events, recurrence of diarrhoea, severity of diarrhoea according to the Vesikari Scale and use of concomitant medications.
ResultsSixty-four children (89%) completed the intervention and were included in the analysis. The duration of diarrhoea after randomisation was similar in the gelatine tannate and placebo groups (75.6±27.8 vs 75.5±29.0 hours, respectively, mean difference 0.1 hours, 95% CI –14.1 to 14.3 hours). There was no significant difference between groups in the number of watery stools per day throughout the study period. There were also no differences in any other secondary outcome measures between groups.
ConclusionIn children with AGE younger than 5 years of age, gelatine tannate was ineffective as an adjunct to rehydration therapy.
Trial registration numberIntroduction
Physical training may play a prominent role in the development of preadolescent brains, but it is yet to be determined what type of exercise may generate higher cognitive effects, and if concurrent mental engagement provides further efficacy. The aim of this study is to investigate motor and cognitive effects of a 9-week exercise intervention in children aged 6–10 years. Trainings include the automatisation of challenging coordination exercises with concurrent mental tasks (intervention group) and multisport exercises with and without mental tasks (two control groups). It is hypothesised that all groups gain motor and cognitive effects, but highest benefits are expected for the combination of automatised coordination exercises with mental tasks.
Methods and analysisTwo elementary schools (~500 students) take part in the study. Data are generated by using the German Motor Performance Test 6–18 (Deutscher Motorik-Test 6–18), TDS (Match 4 Point), d2-R test of attention and Kasel-Concentration-Task for Children Aged 3–8 Years; test-duration: 6–7 min. After pretesting in September 2017 and a 9-week training intervention, post-testing takes place in December 2017 and March 2018 (long-term effects). Training interventions consist of coordination exercises with concurrent mental tasks (intervention group) and multimotor exercises with and without concurrent mental tasks (control groups). Shapiro-Wilk test will be used to test for normal distribution and the Levene test for variance homogeneity. The appropriate multivariate statistical methods (multivariate analysis of variance or Kruskal-Wallis test) will be used for analysing differences among the groups and for comparing preintervention with postintervention performances.
Ethics and disseminationAll procedures have been approved by the board for ethical questions in science of the University of Innsbruck. Findings will be published in 2018 in international journals and presented at conferences. Schools will be informed of key results.
Objective
To quantify the effect of intrahospital patient flow on emergency department (ED) performance targets and indicate if the expectations set by the National Health Service (NHS) England 5-year forward review are realistic in returning emergency services to previous performance levels.
DesignLinear regression analysis of routinely reported trust activity and performance data using a series of cross-sectional studies.
SettingNHS trusts in England submitting routine nationally reported measures to NHS England.
Participants142 acute non-specialist trusts operating in England between 2012 and 2016.
Main outcome measuresThe primary outcome measures were proportion of 4-hour waiting time breaches and cancelled elective operations.
MethodsUnivariate and multivariate linear regression models were used to show relationships between the outcome measures and various measures of trust activity including empty day beds, empty night beds, day bed to night bed ratio, ED conversion ratio and delayed transfers of care.
ResultsUnivariate regression results using the outcome of 4-hour breaches showed clear relationships with empty night beds and ED conversion ratio between 2012 and 2016. The day bed to night bed ratio showed an increasing ability to explain variation in performance between 2015 and 2016. Delayed transfers of care showed little evidence of an association. Multivariate model results indicated that the ability of patient flow variables to explain 4-hour target performance had reduced between 2012 and 2016 (19% to 12%), and had increased in explaining cancelled elective operations (7% to 17%).
ConclusionsThe flow of patients through trusts is shown to influence ED performance; however, performance has become less explainable by intratrust patient flow between 2012 and 2016. Some commonly stated explanatory factors such as delayed transfers of care showed limited evidence of being related. The results indicate some of the measures proposed by NHS England to reduce pressure on EDs may not have the desired impact on returning services to previous performance levels.
Objectives
To determine the prevalence of alcohol-related presentations in all 29 emergency departments (EDs) in Ireland and compare with non-alcohol-related presentations in order to identify opportunities for improvements in the quality of patient care and related data collection.
Design and settingDescriptive prevalence study reviewing all records in the same four 6-hour periods in every 24-hour ED in the country.
Participants3194 persons who attended EDs over four specified 6-hour periods.
Primary outcome measuresThe prevalence of alcohol-related presentations, comparison with non-alcohol-related presentations and the categorisation of these presentations according to WHO International Statistical Classification of Diseases and Related Health Problems 10th Revision codes.
ResultsThe total number of presentations was 3194 in the four 6-hour periods, of whom 189 (5.9%) were alcohol related, varying from 29.0% in the early hours of Sunday morning to 1.2% on Monday morning (p>0.0001). The alcohol-related presentations were more likely to be men, attend on early hours of Sunday morning, arrive by ambulance, leave before being seen by a doctor or leave against medical advice; and they were less likely to be admitted to hospital.
ConclusionsAlcohol-related presentations are a significant burden on EDs and ambulance services, especially in the early hours of Sunday mornings. Addressing the alcohol-related burden on EDs requires improvements in data collection and information systems, the development of appropriate interventions and related referral services and better preventive actions for alcohol-related harm.
Introduction
Continuous ambulatory peritoneal dialysis (CAPD) is the ideal modality for renal replacement therapy in most African settings given that it is relatively cheaper than haemodialysis (HD) and does not require in-centre care. CAPD is, however, not readily utilised as it is often complicated by peritonitis leading to high rates of technique failure. The objective of this study is to assess the prevalence of CAPD-related peritonitis and all-cause mortality in patients treated with CAPD in Africa.
Methods and analysisWe will search PubMed, EMBASE, SCOPUS, Africa Journal Online and Google Scholar for studies conducted in Africa from 1 January 1980 to 30 June 2017 with no language restrictions. Eligible studies will include cross-sectional, prospective observational and cohort studies of patients treated with CAPD. Two authors will independently screen, select studies, extract data and conduct risk of bias assessment. Data consistently reported across studies will be pooled using random-effects meta-analysis. Heterogeneity will be evaluated using Cochrane's Q statistic and quantified using I2 statistics. Graphical and formal statistical tests will be used to assess for publication bias.
Ethics and disseminationEthical approval will not be needed for this study as data used will be extracted from already published studies. Results of this review will be published in a peer-reviewed journal and presented at conferences. The Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015) framework guided the development of this protocol.
PROSPERO registration numberCRD42017072966.
Objectives
Spinal muscular atrophy (SMA) has profound implications for patients and families. The aim of the present study was to gain insights into the effects caring for a child with SMA has on the costs incurred by families caring for a child with SMA from carer perspectives to identify gaps in provision of care, inform public policy and cost-effectiveness analyses.
DesignInterpretive phenomenological analysis guided the delivery and analysis of semi-structured interviews undertaken to explore the financial, opportunity and psychosocial costs associated with caring for children with SMA.
Participants and settingParents of children with SMA types II and III from a single Australian paediatric neuromuscular clinic participated in this study.
ResultsA range of experiences were reported and information saturation (n=7) was reached endorsing themes, including: significant financial and caregiving burdens, adjusted career choices and limitations on career progression and a complex landscape of access to funding, equipment, support and resources. Opportunity costs of foregone employment, purchases and leisure activities were substantial, as were emotional and social impacts. Participants voiced determination and resilience, and called for continued efforts to improve supportive care services and resources.
ConclusionsThe range and nature of costs met by families caring for a child with SMA were found to be expansive and not typically recognised. These include high direct costs associated with goods and services, indirect costs associated with voluntary care, substantial and long-term opportunities foregone in paid employment and career progression and unmeasured or hidden costs associated with mental health burden.
Introduction
In recent times, hypertension has become one of the major public health concerns in both the developed and the developing world and is responsible for death due to heart diseases and stroke. The increasing trend of the prevalence of hypertension in low-income and middle-income countries (LMICs) and it's catastrophic consequences have made the phenomenon important to continue to investigate interventions for its prevention and control. Different dietary and lifestyle-related approaches have been recommended for the prevention of hypertension. The aim of this proposed review is to explore the available non-pharmacological interventions tried for the prevention of hypertension in LMICs.
Methods and analysisEight electronic databases will be searched covering the period between 1990 and 2016 to identify relevant studies and will be screened by two independent reviewers. The searched articles will be included for full-text extraction applying definitive inclusion and exclusion criteria. Appropriate critical appraisal tools including the Cochrane Handbook for Systematic Reviews of Interventions will be used to assess the risk of bias. Disagreement between the two reviewers will be resolved by a third reviewer. Narrative synthesis of the findings will be provided along with summaries of the intervention effect. A meta-analysis will be undertaken using the random-effects model where applicable. Heterogeneity between the studies will be assessed, and sensitivity analysis will be conducted based on study quality.
Ethics and disseminationApproval from the institutional review board has been taken for this review. Findings will be summarised in a single manuscript.
This review is an attempt to explore the available non-pharmacological approaches for the prevention of hypertension in LMICs. Findings from the review will highlight effective non-pharmacological measures for the prevention of hypertension to guide policy for future strategies.
PROSPERO registration numberCRD42017055423.
Introduction
Treatments aiming at reperfusion of the acutely ischaemic brain tissue may result futile or even detrimental because of the so-called reperfusion injury. The processes contributing to reperfusion injury involve a number of factors, ranging from blood–brain barrier (BBB) disruption to circulating biomarkers. Our aim is to evaluate the relative effect of imaging and circulating biomarkers in relation to reperfusion injury.
Methods and analysisObservational hospital-based study that will include 140 patients who had ischaemic stroke, treated with systemic thrombolysis, endovascular treatment or both. BBB disruption will be assessed with CT perfusion (CTP) before treatment, and levels of a large panel of biomarkers will be measured before intervention and after 24 hours. Relevant outcomes will include: (1) reperfusion injury, defined as radiologically relevant haemorrhagic transformation at 24 hours and (2) clinical status 3 months after the index stroke. We will investigate the separate and combined effect of pretreatment BBB disruption and circulating biomarkers on reperfusion injury and clinical status at 3 months. Study protocol is registered at http://www.clinicaltrials.gov (ClinicalTrials.gov ID: NCT03041753).
Ethics and disseminationThe study protocol has been approved by ethics committee of the Azienda Ospedaliero Universitaria Careggi (Università degli Studi di Firenze). Informed consent is obtained by each patient at time of enrolment or deferred when the participant lacks the capacity to provide consent during the acute phase. Researchers interested in testing hypotheses with the data are encouraged to contact the corresponding author. Results from the study will be disseminated at national and international conferences and in medical thesis.
Trial registration numberObjective
To examine the association between disability exclusion and psychological distress.
DesignCross-sectional study.
SettingPopulation-based study of individuals living in households across Australia.
ParticipantsRespondents were persons aged 15 and over living with a disability.
Primary outcome measuresReporting an experience of discrimination or avoidance behaviour due to a respondent's disability. High or very high levels of psychological distress measured using the Kessler K10 instrument.
MethodologyUsing the Survey of Disability, Ageing and Carers, we calculated the prevalence of persons with a disability experiencing psychological distress, disaggregated by experiences of disability exclusion, including discrimination and avoidance. Logistic regression models were fitted to examine the association between disability exclusion and psychological distress, once extensive controls and adjustments for survey design and presence of psychosocial disabilities were considered.
ResultsAbout 62% of persons citing an experience of disability discrimination were in psychological distress, compared with 27% of those citing no discrimination. Furthermore, 53% of those who actively avoided social, familial or economic activities because of their disability experienced psychological distress, compared with 19% of those who did not avoid these situations. After controlling for demographic characteristics and disabling conditions, reporting an experience of disability discrimination or disability avoidance increased the odds of psychological distress by 2.2 (95% CI 1.74 to 2.26) and 2.6 (95% CI 2.28 to 2.97) times, respectively. Those who experienced both avoidance and discrimination were 3.7 (95% CI 2.95 to 4.72) times more likely to be in psychological distress than those experiencing neither. Avoidance and discrimination in healthcare settings were also found to be strongly associated with experiencing psychological distress.
ConclusionsGiven new policy initiatives to improve disability care, coupled with the increasing speed of population ageing, the onus is on governments and its citizenry to address disability exclusion to offset potential mental health impacts.
Objectives
To describe the prevalence of multimorbidity (presence of two or more long-term health conditions) in the New Zealand (NZ) population, and compare risk of health outcomes by multimorbidity status.
DesignCross-sectional analysis for prevalence of multimorbidity, with 1-year prospective follow-up for health outcomes.
SettingNZ general population using national-level routine health data on hospital discharges and pharmaceutical dispensing.
ParticipantsAll NZ adults (aged 18+, n=3 489 747) with an active National Health Index number at the index date (1 January 2014).
Outcome measuresPrevalence of multimorbidity was calculated using two data sources: prior routine hospital discharge data (61 ICD-10 coded diagnoses from the M3 multimorbidity index); and recent pharmaceutical dispensing records (30 conditions from the P3 multimorbidity index).
MethodsPrevalence of multimorbidity was calculated separately for the two data sources, stratified by age group, sex, ethnicity and socioeconomic deprivation, and age and sex standardised to the total population. One-year risk of poor health outcomes (mortality, ambulatory sensitive hospitalisation (ASH) and overnight hospital admission) was compared by multimorbidity status using logistic regression adjusted for confounders.
ResultsPrevalence of multimorbidity was 7.9% using past hospital discharge data, and 27.9% using past pharmaceutical dispensing data. Prevalence increased with age, with a clear socioeconomic gradient and differences in prevalence by ethnicity. Age and sex standardised risk of 1-year mortality was 2.7% for those with multimorbidity (defined on hospital discharge data), and 0.5% for those without multimorbidity (age and sex-adjusted OR 4.8, 95% CI 4.7 to 5.0). Risk of ASH was also increased for those with multimorbidity (eg, pharmaceutical discharge definition: age and sex-standardised risk 6.2%, compared with 1.8% for those without multimorbidity; age and sex-adjusted OR 3.6, 95% CI 3.5 to 3.6).
ConclusionsMultimorbidity is common in the NZ adult population, with disparities in who is affected. Providing for the needs of individuals with multimorbidity requires collaborative and coordinated work across the health sector.
Introduction
Multimorbidity (co-occurring physical and mental illness) is an important issue for clinicians and researchers with combined efforts aimed at promoting the health and well-being of individuals across the life course. In children and youth, experience of any chronic physical illness leads to a substantial increase in risk for mental illness. As a growing field of interest, research is needed to map the current state of the literature in child and youth multimorbidity in order to identify existing gaps and inform the direction of future investigations.
Methods and analysisWe are proposing the conduct of a scoping review to explore the depth and breadth of existing evidence in the field of child and youth multimorbidity. The scoping review will follow the methodological framework developed by Arksey and O'Malley, and will incorporate additional scoping review recommendations made by Levac et al. A systematic search of the following four key databases will be conducted: (1) PubMed; (2) EMBASE; (3) PsycINFO; and (4) Scopus, using combinations of Medical Subject Headings (MeSH) and Emtree terms. We will also consult grey literature sources and hand-search reference lists of included studies to identify additional studies of relevance. For eligible studies that meet all identified inclusion and exclusion criteria, a data extraction tool will be used to collect and store key study characteristics that will be relevant for collating, summarising and reporting the results of the scoping review. This scoping review also presents a novel use of quality index scoring, which we anticipate will contribute to strengthening the rigour of the scoping review methodology.
Ethics and disseminationThe proposed scoping review does not require ethical approval. Final study results will be disseminated via conference presentations, publication in a peer-reviewed journal and knowledge translation activities with relevant stakeholders.
Objectives
To determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway.
DesignA model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion.
SettingExplored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA.
ParticipantsCalculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum.
Main outcome measuresThe primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost-effectiveness analysis.
ResultsResults indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost-effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of £20 000–£30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately £40).
ConclusionUse of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway.
Here, we present a general protocol to prepare a variety of microhoneycomb monoliths (MHMs) in which fluid can pass through with an extremely low pressure drop. MHMs obtained are expected to be used as filters, catalyst supports, flow-type electrodes, sensors and scaffolds for biomaterials.
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Direct-acting anti-viral agents have improved the treatment of chronic hepatitis C virus (HCV) infection, but this treatment is challenging for patients using co-medications because of potential drug–drug inte...
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Objective
Nardilysin (NRDC), a zinc peptidase, exhibits multiple localisation-dependent functions including as an enhancer of ectodomain shedding in the extracellular space and a transcriptional coregulator in the nucleus. In this study, we investigated its functional role in exocrine pancreatic development, homeostasis and the formation of pancreatic ductal adenocarcinoma (PDA).
DesignWe analysed Ptf1a-Cre; Nrdcflox/flox mice to investigate the impact of Nrdc deletion. Pancreatic acinar cells were isolated from Nrdcflox/flox mice and infected with adenovirus expressing Cre recombinase to examine the impact of Nrdc inactivation. Global gene expression in Nrdc-cKO pancreas was analysed compared with wild-type pancreas by microarray analysis. We also analysed Ptf1a-Cre; KrasG12D; Nrdcflox/flox mice to investigate the impact of Nrdc deletion in the context of oncogenic Kras. A total of 51 human samples of pancreatic intraepithelial lesions (PanIN) and PDA were examined by immunohistochemistry for NRDC.
ResultsWe found that pancreatic deletion of Nrdc leads to spontaneous chronic pancreatitis concomitant with acinar-to-ductal conversion, increased apoptosis and atrophic pancreas in mice. Acinar-to-ductal conversion was observed mainly through a non-cell autonomous mechanism, and the expression of several chemokines was significantly increased in Nrdc-null pancreatic acinar cells. Furthermore, pancreatic deletion of Nrdc dramatically accelerated KrasG12D-driven PanIN and subsequent PDA formation in mice. These data demonstrate a previously unappreciated anti-inflammatory and tumour suppressive functions of Nrdc in the pancreas in mice. Finally, absence of NRDC expression was observed in a subset of human PanIN and PDA.
ConclusionNrdc inhibits pancreatitis and suppresses PDA initiation in mice.
The work of Behrens et al1 is an interesting prospective study about sedation-related complications during GI endoscopic procedures, which by the large number of patients involved allows a reliable analysis of their rates and associated risk factors. Major complications occurred more frequently on sedated patients (0.01%) than on non sedated patients (0.007%), with a mortality rate of 0.004% with sedation and only 0.002% without sedation. The majority of complications were respiratory, and of the 38 patients with major complications, 26 required intubation and 13 died.1 It may be useful to look over the pharmacological properties of the selected drugs as a way to predict and avoid adverse outcomes, especially respiratory failure.
The majority of authors use benzodiazepines (midazolam) or propofol, which are GABAergic drugs able to induce a dose-dependent depression of the central nervous system that may eventually result in respiratory failure, which may be caused by two...
In longitudinal electroencephalography (EEG) studies, repeatable electrode positioning is essential for reliable EEG assessment. Conventional methods use anatomical landmarks as fiducial locations for the elec...
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This protocol describes methods to record the auditory brainstem response from postnatal rat pups. To examine the functional development of outer hair cells, the experimental procedure of whole-cell patch clamp recording in isolated outer hair cells is described step-by-step.
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Despite continued efforts to develop new therapies for glioblastoma, none have been able to improve how long patients live appreciably. Despite some setbacks, researchers are hopeful that immunotherapy might be able to succeed where other therapies have not.
LAKEVILLE, Minn. — ImageTrend, Inc. announced the availability of a feature for Positive Identification of EMS personnel for the handling of controlled substances. This function employs a list of challenge questions that can be randomly generated at time of signature when documenting a controlled substance within a patient care report to verify the identity of the logged in medic. "A completely ...
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Veteran paramedic David Blackstone recently had hip surgery, but he hopes to return to the EMS industry when he is back on his feet
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Celebrating those who spend their days and nights helping others when they need help the most during EMS Week 2018
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In the publication of this article [1], there was an error in Figs. 2, 3 and 6.
Cancers, Vol. 10, Pages 158: Beyond the Edge of Hypomethylating Agents: Novel Combination Strategies for Older Adults with Advanced MDS and AML
Cancers doi: 10.3390/cancers10060158
Authors: Anne Sophie Kubasch Uwe Platzbecker
Higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) of the elderly exhibit several commonalities, including first line treatment with hypomethylating agents (HMA) like azacitidine (AZA) or decitabine (DAC). Until today, response to treatment occurs in less than 50 percent of patients, and is often short-lived. Moreover, patients failing HMA have a dismal prognosis. Current developments include combinations of HMA with novel drugs targeting epigenetic or immunomodulatory pathways. Other efforts focus on the prevention of resistance to HMA using checkpoint inhibitors to enhance immune attack. This review focuses on recent advances in the field of HMA-based front-line therapies in elderly patients with myeloid diseases.
New drugs against advanced melanoma have emerged during last decade. Target therapy and immunotherapy have changed the management of patients with metastatic disease. Along with its generalized use, drug toxicities have appeared and the skin is the target organ of a significant part of them. This revision summarizes the most common side effects and consensus management to improve the compliance of therapies and patients' quality of life. Among the BRAF inhibitors, main cutaneous side effects are photosensitivity, plantar hyperkeratosis, and the appearance of verrucal keratosis or squamous cell carcinoma. Special attention must be paid to the development of new primary melanomas or changes on nevi during BRAF inhibitor therapy. The most common cutaneous side effects of immunotherapy are rash, pruritus, and vitiligo. It remains controversial the possible role of these toxicities as markers of response to therapy.
A 79-year-old female with a history of keratoconjunctivitis sicca presented with several years of epiphora of both eyes. Thirteen years earlier, intracanalicular Herrick lacrimal plugs (Lacrimedics, Eastsound, WA, USA) had been placed in both eyes to treat her dry eye syndrome. After 13 years the patient felt the epiphora was intolerable and underwent endoscopic dacryocystorhinostomy (DCR) of the left, then the right side. Intraoperatively, during the right endoscopic DCR, a Herrick lacrimal plug was found in the common canaliculus into the lacrimal sac. Postoperatively, the patient did well with improved epiphora. The Herrick plug is designed to be intracanalicular, and this case illustrates that the plug can migrate and be retained for many years. Collared punctal plugs have a lower risk of this type of complication.
Case Rep Ophthalmol 2018;9:283–286
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Conjunctivitis, keratoconjunctivitis, and corneal ulcers are common eye disorders frequently diagnosed in both humans and animals, and are currently treated by topical administration of eye drops containing anti-inflammatory and antibacterial agents. The current molecules often lack efficacy because infections in hypoxic tissue contain methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa; thus, new products for the treatment of ocular pain and inflammation are needed. The use of ozone, a molecule stabilized for topical use as an ozonide, could be providential due to its anti-inflammatory and bactericidal activity in certain anterior segment pathologies, in addition to promoting tissue repair properties. Ozonated oils have the same properties as gaseous ozone and are well tolerated by tissues. In the present study the repair and regeneration effect of ozonated oil in liposomes plus hypromellose (Ozodrop®, FB Vision, Ascoli Piceno, Italy) instilled 3–4 times a day in external ocular spontaneous pathologies both in animals and humans are reported.
Case Rep Ophthalmol 2018;9:287–298
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We present a case of a young female with a slowly progressing visual impairment who was examined with multifocal visual evoked potentials and functional magnetic resonance imaging (fMRI) for underlying neuronal abnormality. The fMRI examination consisted of presenting black-and-white checkerboard stimuli, and her activation patterns were compared to the patterns from 4 normal-sighted subjects. The results showed clear differences in neuronal activation between the patient and the controls in the occipital and parietal lobes. Although we have shown neuronal correlates in a case of unexplained visual loss, it is still an open question as to whether this has an organic or functional cause, which should be the subject for future research.
Case Rep Ophthalmol 2018;9:269–278
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We report a case of patient dissatisfaction after sequential myopic and hyperopic LASIK in the same eye. We discuss the course of management for this patient involving eventual cataract extraction and intraocular lens (IOL) implantation with attention to the IOL power calculation method used.
Case Rep Ophthalmol 2018;9:264–268
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Short- and long-term health-related quality of life (HRQL) was severely affected after surgery. This study aimed to assess the direction and duration of HRQL from 3- to 24-month follow-ups after minimally invasive esophagectomy (MIE) for esophageal cancer.
A systematic literature search in MEDLINE, EMBASE, and the Cochrane database was performed for all potentially relevant studies published until February 2017. Studies were included if they addressed the question of HRQL with OERTC-QLQ-C30 and OES18. Primary outcomes were HRQL change at 3-month follow-up. Secondary outcomes were HRQL change from 3-, 6- (short-term) to 12- (mid-term), and/or 24-month (long-term) follow-ups.
Six articles were included to estimate the change in 24 HRQL outcomes after MIE. Most of the patients' HRQL outcomes deteriorated at short-term follow-up and some lasted to mid- or long-term after MIE. Patients' physical function and global QOL deteriorated from short- to long-term follow-ups, and emotional function had no change. The directions of dyspnea, pain, fatigue, insomnia, constipation, diarrhea, cough, and speech problems were increased. The deterioration in global function lasted 6 months, the increase in constipation and speech problems lasted 12 months, and insomnia increased more than 12 months after MIE.
The emotional function had no change after MIE. The global QOL become worse during early postoperative period; the symptoms of constipation, speech problems, and insomnia increased for a long time after MIE.
Du et al. identify an intermediate "poised" pluripotent state characterized by specific mRNA and miRNA transcriptomes and the ability to contribute to mouse chimeras. ISY1-mediated miRNA regulation is necessary and sufficient for establishing poised pluripotency required for the naive-primed transition, providing an explanation for the early embryonic lethality of global miRNA deficiency.
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Silva and colleagues report that the initiation of X chromosome inactivation takes place in males and on both X chromosomes in females. This is transient and rapid and is triggered by downregulation of naive pluripotent transcription factors during the onset of differentiation.
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Baccarini and colleagues identify a cell-intrinsic feedback mechanism limiting the strength of MEK/ERK and AKT/mTORC1 signals during the activation of hematopoietic stem cells. The mechanism hinges on the negative feedback phosphorylation of MEK1 by activated ERK and is required to prevent HSC exhaustion.
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[Posted 05/24/2018] AUDIENCE: Consumer ISSUE: Lake Michigan Distilling Company, LLC of La Porte, Indiana, doing business as Ethanol Extraction, is recalling its 95% Ethyl Alcohol product ("Product") because of possible contamination with...
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