Anemia of inflammation, also known as anemia of chronic disease, is refractory to erythropoietin (EPO) treatment, but the mechanisms underlying the EPO refractory state are unclear. Here, we ...demonstrate that high mobility group box-1 protein (HMGB1), a damage-associated molecular pattern molecule recently implicated in anemia development during sepsis, leads to reduced expansion and increased death of EPO-sensitive erythroid precursors in human models of erythropoiesis. HMGB1 significantly attenuates EPO-mediated phosphorylation of the Janus kinase 2/STAT5 and mTOR signaling pathways. Genetic ablation of receptor for advanced glycation end products, the only known HMGB1 receptor expressed by erythroid precursors, does not rescue the deleterious effects of HMGB1 on EPO signaling, either in human or murine precursors. Furthermore, surface plasmon resonance studies highlight the ability of HMGB1 to interfere with the binding between EPO and the EPOR. Administration of a monoclonal anti-HMGB1 antibody after sepsis onset in mice partially restores EPO signaling in vivo. Thus, HMGB1-mediated restriction of EPO signaling contributes to the chronic phase of anemia of inflammation.
Resection arthroplasty for failed shoulder arthroplasty Muh, Stephanie J., MD; Streit, Jonathan J., MD; Lenarz, Christopher J., MD ...
Journal of shoulder and elbow surgery,
02/2013, Letnik:
22, Številka:
2
Journal Article
Recenzirano
Background As shoulder arthroplasty becomes more common, the number of failed arthroplasties requiring revision is expected to increase. When revision arthroplasty is not feasible, resection ...arthroplasty has been used in an attempt to restore function and relieve pain. Although outcomes data for resection arthroplasty exist, studies comparing the outcomes after the removal of different primary shoulder arthroplasties have been limited. Materials and methods This was a retrospective multicenter review of 26 patients who underwent resection arthroplasty for failure of a primary arthroplasty at a mean follow-up of 41.8 months (range, 12-130 months). Resection arthroplasty was performed for 6 failed total shoulder arthroplasties (TSAs), 7 failed hemiarthroplasties, and 13 failed reverse TSAs. Results Patients who underwent resection arthroplasty demonstrated significant improvement in visual analog scale pain score (6 ± 4 preoperatively to 3 ± 2 postoperatively). Mean active forward flexion and mean active external rotation decreased, but this difference was not significant. Subgroup analysis revealed that postoperative mean active forward flexion was significantly greater in patients undergoing resection arthroplasty after failed TSA than after reverse TSA ( P = .01). Conclusions Resection arthroplasty is effective in relieving pain, but patients have poor postoperative function. Patients with resection arthroplasty for failed reverse shoulder arthroplasty have worse function than those with failed hemiarthroplasty or TSA. Surgeons should be aware of this when assessing postoperative function. There is no difference in functional outcome between hemiarthroplasty and TSA.
TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation ...of this "cholinergic antiinflammatory pathway" inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents.
Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the ...tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016.
We analysed 15 943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate.
Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9·02 million (95% uncertainty interval UI 8·05–10·16) and the number of tuberculosis deaths was 1·21 million (1·16–1·27). Among HIV-positive individuals, the number of incident cases was 1·40 million (1·01–1·89) and the number of tuberculosis deaths was 0·24 million (0·16–0·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (–1·3% –1·5 to −1·2) than mortality did (–4·5% –5·0 to −4·1) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was −4·0% (–4·5 to −3·7) and mortality was −8·9% (–9·5 to −8·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13·7 for incidence and 14·9 for mortality), and the lowest ratios were in high-income North America (0·4 for incidence) and Oceania (0·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67·3 for incidence and 73·0 for mortality), and high-income North America had the lowest ratios (0·4 for incidence and 0·5 for mortality).
If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV.
Bill & Melinda Gates Foundation.
IDH1 and IDH2 are hotspot mutations commonly identified in WHO-grade 4 astrocytomas. Their association with TAMs has never been investigated. We aim to explore the crosstalk between the IDH1/2 ...mutation metabolic effect and TAMs in tumour microenvironment and how this relationship affects the tumour recurrence.
The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1
and IDH2
was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry.
IDH1
and IDH2
were symmetrically identified as wildtype in 18/20 tumours (90%) and the remaining 2 tumours (10%) showed synonymous mutations on both codons. Tumours with IDH1/2-wildtype showed high expression of CD204
TAMs in 10 cases and low expression in 8 cases. Typical expression was seen equally in IDH1/2 mutant tumours. There was no significant association between IDH1/2 and CD204
TAM expression (p= 0.999). The association between the two groups was significantly observed among IDH-wildtype tumours (p=0.027). Highly expressed CD204 in IDH-wildtype tumours showed a median recurrence at 10 months compared to low CD204 expression, showed a median recurrence interval at 24 months.
IDH1
or IDH
has the same impact on the classification and prognosis of WHO-grade 4 astrocytoma. There was no crosstalk between IDH1/2 metabolic effect and CD204
TAM. However, IDH-wildtype glioblastomas with dense CD204
TAM are associated with early recurrence. Because the sample size is small, a larger study is recommended to determine the impact of IDH1/2 on TAMs.
We introduce the open-source package MercuryDPM, which we have been developing over the last few years. MercuryDPM is a code for discrete particle simulations. It simulates the motion of particles by ...applying forces and torques that stem either from external body forces, (gravity, magnetic fields, etc.) or particle interactions. The code has been developed extensively for granular applications, and in this case these are typically (elastic, plastic, viscous, frictional) contact forces or (adhesive) short-range forces. However, it could be adapted to include long-range (molecular, self-gravity) interactions as well.
MercuryDPM is an object-oriented algorithm with an easy-to-use user interface and a flexible core, allowing developers to quickly add new features. It is parallelised using MPI and released under the BSD 3-clause licence. Its open-source developers’ community has developed many features, including moving and curved walls; state-of-the-art granular contact models; specialised classes for common geometries; non-spherical particles; general interfaces; restarting; visualisation; a large self-test suite; extensive documentation; and numerous tutorials and demos. In addition, MercuryDPM has three major components that were originally invented and developed by its team: an advanced contact detection method, which allows for the first time large simulations with wide size distributions; curved (non-triangulated) walls; and multicomponent, spatial and temporal coarse-graining, a novel way to extract continuum fields from discrete particle systems. We illustrate these tools and a selection of other MercuryDPM features via various applications, including size-driven segregation down inclined planes, rotating drums, and dosing silos.
Program Title: MercuryDPM
Program Files doi: http://dx.doi.org/10.17632/n7jmdrdc52.1
Licensing provisions: BSD 3-Clause
Programming language: C++, Fortran
Supplementary material: http://mercurydpm.org
Nature of problem: Simulation of granular materials, i.e. conglomerations of discrete, macroscopic particles. The interaction between individual grains is characterised by a loss of energy, making the behaviour of granular materials distinct from atomistic materials, i.e. solids, liquids and gases.
Solution method: MercuryDPM (Thornton et al., 2013, 2019; Weinhart et al., 2016, 2017, 2019) is an implementation of the Discrete Particle Method (DPM), also known as the Discrete Element Method (DEM) (Cundall and Strack, 1979). It simulates the motion of individual particles by applying forces and torques that stem either from external forces (gravity, magnetic fields, etc.) or from particle-pair and particle–wall interactions (typically elastic, plastic, dissipative, frictional, and adhesive contact forces). DPM simulations have been successfully used to understand the many unique granular phenomena – sudden phase transitions, jamming, force localisation, etc. – that cannot be explained without considering the granular microstructure.
Unusual features: MercuryDPM was designed ab initio with the aim of allowing the simulation of realistic geometries and materials found in industrial and geotechnical applications. It thus contains several bespoke features invented by the MercuryDPM team: (i) a neighbourhood detection algorithm (Krijgsman et al., 2014) that can efficiently simulate highly polydisperse packings, which are common in industry; (ii) curved walls (Weinhart et al., 2016) making it possible to model real industrial geometries exactly, without triangulation errors; and (iii) MercuryCG (Weinhart et al., 2012, 2013, 2016; Tunuguntla et al., 2016), a state-of-the-art analysis tool that extracts local continuum fields, providing accurate analytical/rheological information often not available from experiments or pilot plants. It further contains a large range of contact models to simulate complex interactions such as elasto-plastic deformation (Luding, 2008), sintering (Fuchs et al., 2017), melting (Weinhart et al., 2019), breaking, wet and dry cohesion (Roy et al., 2016, 2017), and liquid migration (Roy et al., 2018), all of which have important industrial applications.
•MercuryDPM is an open-source software for discrete particle simulations.•Its advanced contact detection allows large simulations with wide size distributions.•It supports curved (non-triangulated) walls to better capture the process geometry.•MercuryCG extracts local continuum fields, providing accurate analytical information.
Background Tranexamic acid (TXA) is an antifibrinolytic agent that has been shown to significantly reduce blood loss and transfusion requirements after total knee and hip arthroplasty. The purpose of ...this study was to evaluate the effect of TXA on postoperative blood loss after shoulder arthroplasty. Methods A total of 111 patients (62 women; average age, 67 years) who underwent shoulder arthroplasty were prospectively randomized in double-blinded fashion to receive either 100 mL of normal saline or 100 mL of normal saline with 2 g TXA by topical application into the wound at the completion of the case. All patients received a postoperative drain. Drain output representing postoperative blood loss, transfusion requirements, and change in hemoglobin level were recorded. All postoperative complications were noted. Results The average blood loss recorded after surgery was 170 mL in the placebo group and 108 mL in the TXA group ( P = .017). The average change in hemoglobin level was 2.6 g/dL in the placebo group and 1.7 g/dL in the TXA group ( P < .001). There were no transfusion requirements or postoperative complications noted in either group. Discussion In this cohort of patients, those treated with TXA experienced a significantly lower amount of postoperative blood loss and a significantly smaller change in hemoglobin level compared with those treated with placebo. Further work is required to determine the effectiveness and clinical significance of TXA in reducing transfusion requirements in shoulder arthroplasty and, more specifically, shoulder arthroplasty performed for complicated patients or for trauma and fracture patients.
COVID-19 pandemic hit the entire world with severe health and economic consequences. Although the infection primarily affected the respiratory system, it was soon recognized that COVID-19 has a ...multi-systemic component with various manifestations including cutaneous involvement.
The main objective of this study is to assess the incidence and patterns of cutaneous manifestations among moderate-to-severe COVID-19 patients who required hospitalization and whether there was a prognostic indication for cutaneous involvement and the outcome in terms of recovery or death.
This is a cross-sectional observational study that included inpatients who were diagnosed with a moderate or severe COVID-19 infection. The demographic and clinical data of patients were assessed including age, sex, smoking, and comorbidities. All patients were examined clinically for the presence of skin manifestations. Patients were followed for the outcome of COVID-19 infection.
A total of 821 patients (356 females and 465 males) aged 4-95 years were included. More than half of patients (54.6%) aged >60 years. A total of 678 patients (82.6%) had at least one comorbid condition, mostly hypertension and diabetes mellitus. Sixty-two patients (7.55%) developed rashes; 5.24% cutaneous and 2.31% oral. The rashes were then grouped into five major types: group A, Exanthema: morbilliform, papulovesicular, varicella-like. Group B, Vascular: Chilblain-like lesions, purpuric/petechial, livedoid lesions. Group C, Reactive erythemas: Urticaria, Erythema multiforme. Group D, other skin rashes including flare-up of pre-existing disease, and O for oral involvement. Most patients (70%) developed rash after admission. The most frequent skin rashes were reactive erythema (23.3%), followed by vascular (20.9%), exanthema (16.3%), and other rashes with flare-ups of pre-existing diseases (39.5%). Smoking and loss of taste were associated with the appearance of various skin rashes. However, no prognostic implications were found between cutaneous manifestations and outcome.
COVID-19 infection may present with various skin manifestations including worsening of pre-existing skin diseases.
The coasts and islands that flank Abu Dhabi, the United Arab Emirates (UAE)’s largest emirate, host the country’s most significant coastal and marine habitats including coral reefs. These reefs, ...although subject to a variety of pressures from urban and industrial encroachment and climate change, exhibit the highest thresholds for coral bleaching and mortality in the world. By reviewing and benchmarking global, regional and local coral reef conservation efforts, this study highlights the ecological importance and economic uniqueness of the UAE corals in light of the changing climate. The analysis provides a set of recommendations for coral reef management that includes an adapted institutional framework bringing together stakeholders, scientists, and managers. These recommendations are provided to guide coral reef conservation efforts regionally and in jurisdictions with comparable environmental challenges.
The Global Burden of Anemia Kassebaum, Nicholas J
Hematology/oncology clinics of North America,
04/2016, Letnik:
30, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Anemia is an important cause of health loss. We estimated levels and trends of nonfatal anemia burden for 23 distinct etiologies in 188 countries, 20 age groups, and both sexes from 1990 to 2013. All ...available population-level anemia data were collected and standardized. We estimated mean hemoglobin, prevalence of anemia by severity, quantitative disability owing to anemia, and underlying etiology for each population using the approach of the Global Burden of Disease, Injuries and Risk Factors 2013 Study. Anemia burden is high. Developing countries account for 89% of all anemia-related disability. Iron-deficiency anemia remains the dominant cause of anemia.
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