Purpose: A retrospective analysis of real-world data was performed to assess the epidemiology and economic burden of multiple sclerosis (MS), relapsing-remitting MS (RRMS), and secondary-progressive ...MS (SPMS) in Italy. Patients and Methods: An observational study on administrative databases from a sample of Italian entities was carried-out. Between 01/2010-12/2017, patients with greater than or equal to1 MS diagnosis code (ICD-9-CM:340 and/or exemption code:046) and/or greater than or equal to1 disease-modifying therapies (DMTs) prescription, were included. Among MS-cohort, SPMS patients were identified by greater than or equal to2 hospitalizations or by greater than or equal to2 drug prescriptions related to MS progression. MS patients not fulflling SPMS criteria were included as RRMS. Mean annual healthcare costs were reported during follow-up and stratified by DMT treatment/untreatment. Results: Overall, 9543 MS patients were included; 8397 with RRMS and 1146 with SPMS. Estimated prevalence of MS was 141.6/100,000 inhabitants (RRMS 124.4/100,000 and SPMS 17.2/100,000). Mean annual cost for untreated and treated patient was respectively: euro3638 and euro11796 (MS-cohort), euro3183 and euro11486 (RRMS-cohort), euro6317 and euro15511 (SPMS-cohort). The first-line DMT treatment duration averaged 27.4 + or - 22.8 months; the mean cost was 19004euro for the whole period. The second-line DMT treatment lasted on average 31.1 + or - 24.5 months; the mean cost was 47293euro for the whole period. Conclusion: This study provided insights into the MS epidemiology in Italy and its economic burden. Healthcare costs associated with MS management were mainly driven by DMTs expenditure. A trend of higher healthcare-resource consumption was observed among SPMS-cohort. Keywords: real-world evidence, clinical practice, multiple sclerosis, epidemiology, healthcare resource consumption
The first comprehensive review of the current and future effects of climate change on the world's fisheries and aquaculture operations The first book of its kind, Climate Change Impacts on Fisheries ...and Aquaculture explores the impacts of climate change on global fisheries resources and on marine aquaculture. It also offers expert suggestions on possible adaptations to reduce those impacts. The world's climate is changing more rapidly than scientists had envisioned just a few years ago, and the potential impact of climate change on world food production is quite alarming. Nowhere is the sense of alarm more keenly felt than among those who study the warming of the world's oceans. Evidence of the dire effects of climate change on fisheries and fish farming has now mounted to such an extent that the need for a book such as this has become urgent. A landmark publication devoted exclusively to how climate change is affecting and is likely to affect commercially vital fisheries and aquaculture operations globally, Climate Change Impacts on Fisheries and Aquaculture provides scientists and fishery managers with a summary of and reference point for information on the subject which has been gathered thus far. * Covers an array of critical topics and assesses reviews of climate change impacts on fisheries and aquaculture from many countries, including Japan, Mexico, South Africa, Australia, Chile, US, UK, New Zealand, Pacific Islands, India and others * Features chapters on the effects of climate change on pelagic species, cod, lobsters, plankton, macroalgae, seagrasses and coral reefs * Reviews the spread of diseases, economic and social impacts, marine aquaculture and adaptation in aquaculture under climate change * Includes special reports on the Antarctic Ocean, the Caribbean Sea, the Arctic Ocean and the Mediterranean Sea Extensive references throughout the book make this volume both a comprehensive text for general study and a reference/guide to further research for fisheries scientists, fisheries managers, aquaculture personnel, climate change specialists, aquatic invertebrate and vertebrate biologists, physiologists, marine biologists, economists, environmentalist biologists and planners.
Increased portal pressure during variceal bleeding may have an influence on the treatment failure rate, as well as on short- and long-term survival. However, the usefulness of hepatic hemodynamic ...measurement during the acute episode has not been prospectively validated, and no information exists about the outcome of hemodynamically defined high-risk patients treated with early portal decompression. Hepatic venous pressure gradient (HVPG) measurement was made within the first 24 hours after admission of 116 consecutive patients with cirrhosis with acute variceal bleeding treated with a single session of sclerotherapy injection during urgent endoscopy. Sixty-four patients had an HVPG less than 20 mm Hg (low-risk LR group), and 52 patients had an HVPG greater than or equal to 20 mm Hg (high-risk HR group). HR patients were randomly allocated into those receiving transjugular intrahepatic portosystemic shunt (TIPS; HR-TIPS group, n = 26) within the first 24 hours after admission and those not receiving TIPS (HR-non-TIPS group). The HR-non-TIPS group had more treatment failures (50% vs. 12%, P =.0001), transfusional requirements (3.7 +/- 2.7 vs. 2.2 +/- 2.3, P =.002), need for intensive care (16% vs. 3%, P <.05), and worse actuarial probability of survival than the LR group. Early TIPS placement reduced treatment failure (12%, P =.003), in-hospital and 1-year mortality (11% and 31%, respectively; P <.05). In conclusion, increased portal pressure estimated by early HVPG measurement is a main determinant of treatment failure and survival in variceal bleeding, and early TIPS placement reduces treatment failure and mortality in high risk patients defined by hemodynamic criteria.
Background
A high prevalence of tuberculosis (TB) among HIV‐positive injecting drug users (IDUs) may fuel the TB epidemic in the general population of Romania. We determined the frequency and ...characteristics of TB in HIV‐infected IDUs referred to a national centre.
Methods
Prospective observational cohort study of all newly‐diagnosed HIV‐positive IDUs admitted to Victor Babes Hospital, Bucharest, between January 2009 and December 2014. Socio‐demographics, clinical characteristics and outcomes of HIV/TB co‐infected IDUs were compared to HIV‐positive IDUs without TB.
Results
170/598 (28.5%) HIV‐infected IDUs were diagnosed with TB. The prevalence increased from 12.5% in 2009 to 32.1% in 2014 (P < 0.001). HIV/TB co‐infected individuals had lower median CD4 cell counts 75 (vs. 450/mm3, P < 0.0001) and higher median HIV viral loads 5.6 log10 (vs. 4.9 log10, P < 0.0001) when presenting to healthcare services. 103/170 (60.6%) HIV/TB co‐infected IDUs were diagnosed with pulmonary TB. Resistant Mycobacterium tuberculosis strains were common, with 18/105 (17.1%) of patients having Multi‐Drug Resistant (MDR) disease. Higher mortality rate was associated with TB co‐infection (P < 0.0001), extra‐pulmonary TB (P = 0.0026) and extensively drug resistant TB (P = 0.024).
Conclusions
Tuberculosis (TB) is an increasing problem in HIV‐infected IDUs in Romania. Presentation is often with advanced HIV, significant TB drug resistance and consequent outcomes are poor.
The deleterious consequences of fatty acid (FA) and neutral lipid accumulation in nonadipose tissues, such as the heart, contribute to the pathogenesis of type 2 diabetes. To elucidate mechanisms of ...FA-induced cell death, or lipotoxicity, we generated Chinese hamster ovary (CHO) cell mutants resistant to palmitate-induced death and isolated a clone with disruption of eukaryotic elongation factor (eEF) 1A-1. eEF1A-1 involvement in lipotoxicity was confirmed in H9c2 cardiomyoblasts, in which small interfering RNA-mediated knockdown also conferred palmitate resistance. In wild-type CHO and H9c2 cells, palmitate increased reactive oxygen species and induced endoplasmic reticulum (ER) stress, changes accompanied by increased eEF1A-1 expression. Disruption of eEF1A-1 expression rendered these cells resistant to hydrogen peroxide- and ER stress-induced death, indicating that eEF1A-1 plays a critical role in the cell death response to these stressors downstream of lipid overload. Disruption of eEF1A-1 also resulted in actin cytoskeleton defects under basal conditions and in response to palmitate, suggesting that eEF1A-1 mediates lipotoxic cell death, secondary to oxidative and ER stress, by regulating cytoskeletal changes critical for this process. Furthermore, our observations of oxidative stress, ER stress, and induction of eEF1A-1 expression in a mouse model of lipotoxic cardiomyopathy implicate this cellular response in the pathophysiology of metabolic disease.
Fully gapped d-wave superconductivity in CeCu2Si2 Pang, Guiming; Smidman, Michael; Zhang, Jinglei ...
Proceedings of the National Academy of Sciences - PNAS,
05/2018, Letnik:
115, Številka:
21
Journal Article
Recenzirano
Odprti dostop
The nature of the pairing symmetry of the first heavy fermion superconductor CeCu2Si2 has recently become the subject of controversy. While CeCu2Si2 was generally believed to be a d-wave ...superconductor, recent low-temperature specific heat measurements showed evidence for fully gapped superconductivity, contrary to the nodal behavior inferred from earlier results. Here, we report London penetration depth measurements, which also reveal fully gapped behavior at very low temperatures. To explain these seemingly conflicting results, we propose a fully gapped d+d band-mixing pairing state for CeCu2Si2, which yields very good fits to both the superfluid density and specific heat, as well as accounting for a sign change of the superconducting order parameter, as previously concluded from inelastic neutron scattering results.
1 Vascular Biology Group, Robarts Research Institute,
2 London Health Sciences Centre,
3 Departments of Medicine, Biochemistry and Medical Biophysics, and
4 Department of Physiology and Pharmacology, ...The University of Western Ontario, London, Ontario, Canada
Submitted 10 August 2009
; accepted in final form 16 October 2009
Polyploid endothelial cells are found in aged and atherosclerotic arteries. However, whether increased chromosome content has an impact on endothelial cell function is unknown. We show here that human aortic endothelial cells become tetraploid as they approach replicative senescence. Furthermore, accumulation of tetraploid endothelial cells was accelerated during growth in high glucose. Interestingly, induction of polyploidy was completely prevented by modest overexpression of the NAD + regenerating enzyme, nicotinamide phosphoribosyltransferase (Nampt). To determine the impact of polyploidy on endothelial cell function, independent of replicative senescence, we induced tetraploidy using the spindle poison, nocodazole. Global gene expression analyses of tetraploid endothelial cells revealed a dysfunctional phenotype characterized by a cell cycle arrest profile (decreased CCNE2/A2 , RBL1 , BUB1B ; increased CDKN1A ) and increased expression of genes involved in inflammation ( IL32 , TNFRSF21/10C , PTGS1 ) and extracellular matrix remodeling ( COL5A1 , FN1 , MMP10/14 ). The protection from polyploidy conferred by Nampt was not associated with enhanced poly(ADP-ribose) polymerase-1 or sirtuin (SIRT) 2 activity, but with increased SIRT1 activity, which reduced cellular reactive oxygen species and the associated oxidative stress stimulus for the induction of polyploidy. We conclude that human aortic endothelial cells are prone to chromosome duplication that, in and of itself, can induce characteristics of endothelial dysfunction. Moreover, the emergence of polyploid endothelial cells during replicative aging and glucose overload can be prevented by optimizing the Nampt-SIRT1 axis.
endothelial cells; senescence; oxidative stress
Address for reprint requests and other correspondence: J. Geoffrey Pickering, London Health Sciences Centre, 339 Windermere Rd., London, Ontario, Canada N6A 5A5 (e-mail: gpickering{at}robarts.ca ).
Electron correlations play a central role in iron-based superconductors. In these systems, multiple Fe
3
d
-orbitals are active in the low-energy physics, and they are not all degenerate. For these ...reasons, the role of orbital-selective correlations has been an active topic in the study of the iron-based systems. In this article, we survey the recent developments on the subject. For the normal state, we emphasize the orbital-selective Mott physics that has been extensively studied, especially in the iron chalcogenides, in the case of electron filling
n
∼
6
. In addition, the interplay between orbital selectivity and electronic nematicity is addressed. For the superconducting state, we summarize the initial ideas for orbital-selective pairing and discuss the recent explosive activities along this direction. We close with some perspectives on several emerging topics. These include the evolution of the orbital-selective correlations, magnetic and nematic orders, and superconductivity as the electron filling factor is reduced from 6 to 5, as well as the interplay between electron correlations and topological band structure in iron-based superconductors.
Motivated by the studies of the superconducting pairing states in the iron-based superconductors, we analyze the effects of Brillouin zone folding procedure from a space-group symmetry perspective ...for a general class of materials with the P4/nmm space group. The Brillouin zone folding amounts to working with an effective 1-Fe unit cell, instead of the crystallographic 2-Fe unit cell. We show that the folding procedure can be justified by the validity of a glide reflection symmetry throughout the crystallographic Brillouin zone and by the existence of a minimal double degeneracy along the edges of the latter. We also demonstrate how the folding procedure fails when a local spin-orbit coupling is included although the latter does not break any of the space-group symmetries of the bare Hamiltonian. In light of these general symmetry considerations, we further discuss the implications of the glide reflection symmetry for the superconducting pairing in an effective multiorbital t-J1-J2 model. We find that, for spin-singlet pairing states, the P4/nmm space-group symmetry allows only even parity under the glide reflection and zero total momentum.
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