Showing papers by "Saint Louis University published in 2018"
TL;DR: Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression are discussed.
Abstract: There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression.
2,004 citations
TL;DR: The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as the authors look ahead to future combination therapies that address symptoms as well as disease progression.
Abstract: Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-β proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression.
821 citations
TL;DR: The Global Burden of Disease study data and methodologies were used to describe the change in burden of CKD from 1990 to 2016 involving incidence, prevalence, death, and disability-adjusted-life-years (DALYs).
507 citations
The Heart Research Institute1, Saint Louis University2, Wake Forest University3, University of Maryland, Baltimore4, Heidelberg University5, University of Florida6, University of Milan7, University of Miami8, University of Erlangen-Nuremberg9, Université du Québec à Montréal10, University of Otago11, University of Adelaide12, Agostino Gemelli University Polyclinic13, United States Department of Veterans Affairs14, Tufts University15, Kyung Hee University16, Dalhousie University17, King's College London18, Sichuan University19, The Chinese University of Hong Kong20, University of Western Australia21, National Institutes of Health22, National University of Singapore23, Uppsala University24, University of São Paulo25, Memorial Hospital of South Bend26, Vrije Universiteit Brussel27, Maastricht University28, Universidad Pública de Navarra29, Centre Hospitalier Universitaire de Toulouse30
TL;DR: Evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR) are presented.
Abstract: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefitharm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
466 citations
Center for Drug Evaluation and Research1, Stanford University2, Icahn School of Medicine at Mount Sinai3, Cleveland Clinic4, Brigham and Women's Hospital5, San Francisco VA Medical Center6, Center for Devices and Radiological Health7, University Hospitals of Cleveland8, Harvard University9, Beth Israel Deaconess Medical Center10, Clinical Trial Service Unit11, University Health Network12, Yale University13, University of Glasgow14, Duke University15, Scripps Health16, Janssen Pharmaceutica17, Saint Louis University18
TL;DR: This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration.
383 citations
TL;DR: Treatment with subcutaneously administered pegbelfermin for 16 weeks was generally well tolerated and significantly reduced hepatic fat fraction in patients with non-alcoholic steatohepatitis, and the full planned sample size was not needed.
347 citations
TL;DR: A positive association between ambient air pollution and increased BP and hypertension is indicated andGeographical and socio-demographic factors may modify the pro-hypertensive effects of air pollutants.
333 citations
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Eindhoven University of Technology1, Max Planck Society2, National Scientific and Technical Research Council3, University of Groningen4, Flinders University5, University of Oxford6, Illinois Institute of Technology7, Nottingham Trent University8, Bielefeld University9, University of Nevada, Las Vegas10, University of Wisconsin-Madison11, Missouri State University12, University of Arkansas13, Katholieke Universiteit Leuven14, Leiden University15, Linnaeus University16, Tzu Chi University17, University of British Columbia18, University of Cambridge19, University of Edinburgh20, Bangor University21, University of Glasgow22, Linköping University23, Florida State University24, Yale University25, University of Louisiana at Lafayette26, St. Edward's University27, University of Texas at Austin28, West Virginia University29, Rutgers University30, Indiana University31, RWTH Aachen University32, Keele University33, University of Tübingen34, Radboud University Nijmegen35, University of Chester36, New York University37, University of Nottingham38, Erasmus University Rotterdam39, University of Bristol40, Sahlgrenska University Hospital41, Adam Mickiewicz University in Poznań42, University of Connecticut43, Charité44, Humboldt University of Berlin45, University of Fribourg46, University of Kent47, Academy of Sciences of the Czech Republic48, RAND Corporation49, Baylor University50, Virginia Tech51, Northern Illinois University52, Open University53, King's College London54, Stanford University55, Karolinska Institutet56, Stockholm University57, Universidade Federal de Santa Catarina58, University of Tromsø59, DePaul University60, Boğaziçi University61, University of Cologne62, King Abdulaziz City for Science and Technology63, University of Leeds64, University of Virginia65, Center for Open Science66, National Institutes of Health67, University of Southern Indiana68, Autonomous University of Madrid69, Utrecht University70, Tilburg University71, Massey University72, Saint Louis University73, University of California, Davis74, Ghent University75
TL;DR: In response to recommendations to redefine statistical significance to P ≤ 0.005, it is proposed that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
Abstract: In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
296 citations
TL;DR: The fusion‐tag solubilized, recombinant form of TDP‐43 full‐length protein developed here will enable future phase separation and in vitro biochemical assays on TDP43 function and interactions that have been hampered in the past by T DP‐43 aggregation.
Abstract: TDP‐43 is an RNA‐binding protein active in splicing that concentrates into membraneless ribonucleoprotein granules and forms aggregates in amyotrophic lateral sclerosis (ALS) and Alzheimer9s disease Although best known for its predominantly disordered C‐terminal domain which mediates ALS inclusions, TDP‐43 has a globular N‐terminal domain (NTD) Here, we show that TDP‐43 NTD assembles into head‐to‐tail linear chains and that phosphomimetic substitution at S48 disrupts TDP‐43 polymeric assembly, discourages liquid–liquid phase separation (LLPS) in vitro , fluidizes liquid–liquid phase separated nuclear TDP‐43 reporter constructs in cells, and disrupts RNA splicing activity Finally, we present the solution NMR structure of a head‐to‐tail NTD dimer comprised of two engineered variants that allow saturation of the native polymerization interface while disrupting higher‐order polymerization These data provide structural detail for the established mechanistic role of the well‐folded TDP‐43 NTD in splicing and link this function to LLPS In addition, the fusion‐tag solubilized, recombinant form of TDP‐43 full‐length protein developed here will enable future phase separation and in vitro biochemical assays on TDP‐43 function and interactions that have been hampered in the past by TDP‐43 aggregation
275 citations
University of California, San Diego1, Northwestern University2, University of Turin3, University of Bologna4, Saint Louis University5, University of Virginia6, Harvard University7, Icahn School of Medicine at Mount Sinai8, Duke University9, Pinnacle Financial Partners10, Virginia Commonwealth University11, Columbia University12, University of Chicago13, Indiana University14, Newcastle University15, Westmead Hospital16, Arizona State University17
TL;DR: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD, and several important secondary endpoints, including noninvasive biomarkers, long‐term outcomes, and patient‐reported outcomes must be considered.
259 citations
University of California, San Diego1, Northwestern University2, University of Turin3, University of Bologna4, Saint Louis University5, University of Virginia6, Institute of Chartered Accountants of Nigeria7, Harvard University8, Icahn School of Medicine at Mount Sinai9, Duke University10, Pinnacle Financial Partners11, Virginia Commonwealth University12, Columbia University13, University of Chicago14, Indiana University15, Newcastle University16, University of Sydney17, Arizona State University18
TL;DR: A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed as mentioned in this paper, including predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced Liver fibrosis (ELF), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis.
TL;DR: A high prevalence of poor sleep among college students, some sex differences, and distinct patterns of mental health symptoms in relation to sleep problems are documents.
TL;DR: It is reported that the RNA-binding protein ELAVL1/HuR plays a crucial role in regulating ferroptosis in liver fibrosis and is identified as a potential target for the treatment of liver fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy.
Abstract: Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, the molecular mechanisms regulating ferroptosis are largely unknown. In this study, we report that the RNA-binding protein ELAVL1/HuR plays a crucial role in regulating ferroptosis in liver fibrosis. Upon exposure to ferroptosis-inducing compounds, ELAVL1 protein expression was remarkably increased through the inhibition of the ubiquitin-proteasome pathway. ELAVL1 siRNA led to ferroptosis resistance, whereas ELAVL1 plasmid contributed to classical ferroptotic events. Interestingly, upregulated ELAVL1 expression also appeared to increase autophagosome generation and macroautophagic/autophagic flux, which was the underlying mechanism for ELAVL1-enhanced ferroptosis. Autophagy depletion completely impaired ELAVL1-mediated ferroptotic events, whereas autophagy induction showed a synergistic effect with ELAVL1. Importantly, ELAVL1 promoted autophagy activation via binding to the AU-rich elements within the F3 of the 3'-untranslated region of BECN1/Beclin1 mRNA. The internal deletion of the F3 region abrogated the ELAVL1-mediated BECN1 mRNA stability, and, in turn, prevented ELAVL1-enhanced ferroptosis. In mice, treatment with sorafenib alleviated murine liver fibrosis by inducing hepatic stellate cell (HSC) ferroptosis. HSC-specific knockdown of ELAVL1 impaired sorafenib-induced HSC ferroptosis in murine liver fibrosis. Noteworthy, we retrospectively analyzed the effect of sorafenib on HSC ferroptosis in advanced fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. Attractively, ELAVL1 upregulation, ferritinophagy activation, and ferroptosis induction occurred in primary human HSCs from the collected human liver tissue. Overall, these results reveal novel molecular mechanisms and signaling pathways of ferroptosis, and also identify ELAVL1-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis. Abbreviations: ACTA2/alpha-SMA: actin, alpha 2, smooth muscle, aorta; ACTB/beta-actin: actin beta; ARE: AU-rich element; ATG: autophagy related; BDL: bile duct ligation; BECN1: beclin 1; BSO: buthionine sulfoximine; COL1A1: collagen type I alpha 1 chain; ELAVL1/HuR: ELAV like RNA binding protein 1; FDA: fluorescein diacetate; FTH1: ferritin heavy chain 1; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvic transaminase; GPX4: glutathione peroxidase 4; GSH: glutathione; HCC: hepatocellular carcinoma; HSC: hepatic stellate cell; LCM: laser capture microdissection; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MDA: malondialdehydep; NCOA4: nuclear receptor coactivator 4; PTGS2: prostaglandin-endoperoxide synthase 2; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TBIL: total bilirubin; TEM: transmission electron microscopy; TGFB1: trasforming growth factor beta 1; UTR: untranslated region; VA-Lip-ELAVL1-siRNA: vitamin A-coupled liposomes carrying ELAVL1-siRNA.
TL;DR: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time to enable users to calculate temporal trends in biodiversity within and amongst assemblage using a broad range of metrics.
Abstract: Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)).Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.
TL;DR: The Global Burden of Disease study data and methodologies were used to estimate the attributable burden of disease and disability-adjusted life-years of diabetes attributable to PM2·5 air pollution globally and in 194 countries and territories.
TL;DR: The costs of transplantation and dialysis were compared with the use of discrete event simulation over a 10‐year period, and kidney transplantation is cost‐effective across all donor types despite higher costs for marginal organs and innovative living donor practices.
TL;DR: Results of a meta-analysis reveal significant relationships between FTP and major classes of consequences, and between antecedents and FTP, as well as moderating effects of different FTP measures and dimensions.
Abstract: The ability to foresee, anticipate, and plan for future desired outcomes is crucial for well-being, motivation, and behavior. However, theories in organizational psychology do not incorporate time-related constructs such as Future Time Perspective (FTP), and research on FTP remains disjointed and scattered, with different domains focusing on different aspects of the construct, using different measures, and assessing different antecedents and consequences. In this review and meta-analysis, we aim to clarify the FTP construct, advance its theoretical development, and demonstrate its importance by (a) integrating theory and empirical findings across different domains of research to identify major outcomes and antecedents of FTP, and (b) empirically examining whether and how these variables are moderated by FTP measures and dimensions. Results of a meta-analysis of k = 212 studies reveal significant relationships between FTP and major classes of consequences (i.e., those related to achievement, well-being, health behavior, risk behavior, and retirement planning), and between antecedents and FTP, as well as moderating effects of different FTP measures and dimensions. Highlighting the importance of FTP for organizational psychology theories, our findings demonstrate that FTP predicts these outcomes over and above the big five personality traits and mediates the associations between these personality traits and outcomes. (PsycINFO Database Record
01 Jul 2018
TL;DR: Cholinergic synapses are ubiquitous in the human central nervous system and their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions as mentioned in this paper.
Abstract: Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-β proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression.
TL;DR: This review provided a comprehensive screenshot about the studies on WRKY TFs in model plants and in crops of economical relevance, and commented one-by-one on the applications of a suite of new and high-throughput techniques to accelerate the studies of WRKY genes in crops.
Abstract: The WRKY gene family in flowering plants encodes a large group of transcription factors (TFs) that play essential roles in diverse stress responses, developmental, and physiological processes. In t...
TL;DR: An unexpected link between membrane phospholipid remodeling and cholesterol biosynthesis is revealed and it is demonstrated that cholesterol itself acts as a mitogen for ISCs and drives ISC proliferation and tumorigenesis.
01 Jan 2018
TL;DR: In this article, a prospective study of 393 adults with NAFLD who underwent VCTE within 1 year of liver histology analysis (median time, 49 d; interquartile range, 25-78 d), from July 1, 2014, through July 31, 2017.
Abstract: Background & Aims Vibration-controlled transient elastography (VCTE), which measures liver stiffness, has become an important tool for evaluating patients with nonalcoholic fatty liver disease (NAFLD). We aimed to determine the diagnostic accuracy of VCTE in detection of NAFLD in a multicenter cohort of patients. Methods We performed a prospective study of 393 adults with NAFLD who underwent VCTE within 1 year of liver histology analysis (median time, 49 d; interquartile range, 25–78 d), from July 1, 2014, through July 31, 2017. Liver stiffness measurement (LSM) cut-off values for pairwise fibrosis stage and controlled attenuation parameter cut-off values for pairwise steatosis grade were determined using cross-validated area under the receiver operating characteristics curve (AUROC) analyses. Diagnostic statistics were computed at a sensitivity fixed at 90% and a specificity fixed at 90%. Results LSM identified patients with advanced fibrosis with an AUROC of 0.83 (95% CI, 0.79– 0.87) and patients with cirrhosis with an AUROC of 0.93 (95% CI, 0.90–0.97). At a fixed sensitivity, a cut-off LSM of 6.5 kPa excluded advanced fibrosis with a negative predictive value of 0.91, and a cut-off LSM of 12.1 kPa excluded cirrhosis with a negative predictive value of 0.99. At a fixed specificity, LSM identified patients with advanced fibrosis with a positive predictive value of 0.71 and patients with cirrhosis with a positive predictive value of 0.41. Controlled attenuation parameter analysis detected steatosis with an AUROC of 0.76 (95% CI, 0.64–0.87). In contrast, the VCTE was less accurate in distinguishing lower fibrosis stages, higher steatosis grades, or the presence of NASH. Conclusions In a prospective study of adults with NAFLD, we found VCTE to accurately distinguish advanced vs earlier stages of fibrosis, using liver histology as the reference standard.
TL;DR: It is found that antibiotic resistance added $1,383 to the cost of treating a patient with a bacterial infection, which amounts to a national cost of $2.2 billion annually.
Abstract: Antibiotic-resistant infections are a global health care concern. The Centers for Disease Control and Prevention estimates that 23,000 Americans with these infections die each year. Rising infection rates add to the costs of health care and compromise the quality of medical and surgical procedures provided. Little is known about the national health care costs attributable to treating the infections. Using data from the Medical Expenditure Panel Survey, we estimated the incremental health care costs of treating a resistant infection as well as the total national costs of treating such infections. To our knowledge, this is the first national estimate of the costs for treating the infections. We found that antibiotic resistance added $1,383 to the cost of treating a patient with a bacterial infection. Using our estimate of the number of such infections in 2014, this amounts to a national cost of $2.2 billion annually. The need for innovative new infection prevention programs, antibiotics, and vaccines to pre...
TL;DR: DNA methylation patterns in angiosperms are complex, dynamic, and an integral part of genome diversity after millions of years of evolution.
Abstract: DNA methylation is an epigenetic modification required for transposable element (TE) silencing, genome stability, and genomic imprinting. Although DNA methylation has been intensively studied, the dynamic nature of methylation among different species has just begun to be understood. Here we summarize the recent progress in research on the wide variation of DNA methylation in different plants, organs, tissues, and cells; dynamic changes of methylation are also reported during plant growth and development as well as changes in response to environmental stresses. Overall DNA methylation is quite diverse among species, and it occurs in CG, CHG, and CHH (H = A, C, or T) contexts of genes and TEs in angiosperms. Moderately expressed genes are most likely methylated in gene bodies. Methylation levels decrease significantly just upstream of the transcription start site and around transcription termination sites; its levels in the promoter are inversely correlated with the expression of some genes in plants. Methylation can be altered by different environmental stimuli such as pathogens and abiotic stresses. It is likely that methylation existed in the common eukaryotic ancestor before fungi, plants and animals diverged during evolution. In summary, DNA methylation patterns in angiosperms are complex, dynamic, and an integral part of genome diversity after millions of years of evolution.
University of Münster1, John H. Stroger, Jr. Hospital of Cook County2, Albany Medical College3, University of British Columbia4, University of Lübeck5, Saint Louis University6, Medical University of Graz7, University of Pennsylvania8, Mayo Clinic9, Nippon Medical School10, University of Oxford11, Wake Forest University12, University of East Anglia13, University of Florence14, Akdeniz University15, University of Louisville16, Stanford University17, University of North Carolina at Chapel Hill18
TL;DR: In this article, a dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (CHCC2012) was presented to standardize the names and definitions for cutaneous vasculitis.
Abstract: Objective To prepare a dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (CHCC2012) to address vasculitides affecting the skin (D-CHCC). The goal was to standardize the names and definitions for cutaneous vasculitis. Methods A nominal group technique with a facilitator was used to reach consensus on the D-CHCC nomenclature, using multiple face-to-face meetings, e-mail discussions, and teleconferences. Results Standardized names, definitions, and descriptions were adopted for cutaneous components of systemic vasculitides (e.g., cutaneous IgA vasculitis as a component of systemic IgA vasculitis), skin-limited variants of systemic vasculitides (e.g., skin-limited IgA vasculitis, drug-induced skin-limited antineutrophil cytoplasmic antibody-associated vasculitis), and cutaneous single-organ vasculitides that have no systemic counterparts (e.g., nodular vasculitis). Cutaneous vasculitides that were not included in the CHCC2012 nomenclature were introduced. Conclusion Standardized names and definitions are a prerequisite for developing validated classification and diagnostic criteria for cutaneous vasculitis. Accurate identification of specifically defined variants of systemic and skin-limited vasculitides requires knowledgeable integration of data from clinical, laboratory, and pathologic studies. This proposed nomenclature of vasculitides affecting the skin, the D-CHCC, provides a standard framework both for clinicians and for investigators.
TL;DR: The current state of the literature on bone defects is reviewed here, with a focus on defining critical-size bone defect, the use of the induced membrane technique, the role of biologics, and the management of infected bone defects.
Abstract: There is a significant burden of disease associated with bone defects, and their management is challenging. These injuries have a profound clinical and economic impact, and outcomes are limited by high rates of complication and reoperation, as well as poor functional outcomes. There remains a lack of consensus around definitions, reliable models, and best practices for the surgical management of bone defects. The current state of the literature on bone defects is reviewed here, with a focus on defining critical-size bone defect, the use of the induced membrane technique, the role of biologics, and the management of infected bone defects.
TL;DR: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL‐17A, has been shown to have significant efficacy and a favourable safety profile in the treatment of moderate‐to‐severe psoriasis and psoriatic arthritis.
Abstract: Background Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy and a favourable safety profile in the treatment of moderate-to-severe psoriasis and psoriatic arthritis. Objective To assess the efficacy and safety of secukinumab through 5 years of treatment in moderate-to-severe psoriasis. Methods In the core SCULPTURE study, Psoriasis Area and Severity Index (PASI) 75 responders at Week 12 continued receiving subcutaneous secukinumab until Year 1. Thereafter, patients entered the extension phase and continued treatment as per the core trial. Treatment was double-blinded until the end of Year 3 and open-label from Year 4. Here, we focus on the 300 mg fixed-interval (every 4 weeks) treatment, the recommended per label dose. Efficacy data are primarily reported as observed, but multiple imputation (MI) and last observation carried forward (LOCF) techniques were also undertaken as supportive analyses. Results At Year 1, 168 patients entered the extension study and at the end of Year 5, 126 patients completed 300 mg (every 4 weeks) treatment. PASI 75/90/100 responses at Year 1 (88.9%, 68.5% and 43.8%, respectively) were sustained to Year 5 (88.5%, 66.4% and 41%). PASI responses were consistent regardless of the analysis undertaken (as observed, MI, or LOCF). The average improvement in mean PASI was approximately 90% through 5 years compared with core study baseline. DLQI (dermatology life quality index) 0/1 response also sustained through 5 years (72.7% at Year 1 and 65.5% at Year 5). The safety profile of secukinumab remained favourable, with no cumulative or unexpected safety concerns identified. Conclusion Secukinumab 300 mg treatment delivered high and sustained levels of skin clearance and improved quality of life through 5 years in patients with moderate-to-severe psoriasis. Favourable safety established in the secukinumab phase 2/3 programme was maintained through 5 years.
TL;DR: Long-term exposure to air pollution was associated with increased risk of diabetes in the Chinese population, particularly in individuals who were younger or overweight or obese.
TL;DR: It is argued that algorithmic judgment should be considered distinct from journalists’ professional judgment based on the twin beliefs that human subjectivity is inherently suspect and in need of replacement, while algorithms are inherently objective and in needs of implementation.
Abstract: Journalistic judgment is both a central and fraught function of journalism. The privileging of objectivity norms and the externalization of newsworthiness in discourses about journalism leave littl...
TL;DR: Three ER-resident proteins (Aster-A, -B, -C) that bind cholesterol and facilitate its removal from the plasma membrane are described to identify a nonvesicular pathway for plasma membrane to ER sterol trafficking in mammals.
Cedars-Sinai Medical Center1, Cornell University2, Northwestern University3, University of California, San Francisco4, University of Texas Southwestern Medical Center5, Cleveland Clinic6, University of Arkansas at Little Rock7, University of Pittsburgh8, Baylor University9, Drexel University10, Mayo Clinic11, Saint Louis University12, Emory University13, Johns Hopkins University14, Henry Ford Health System15, Mount Sinai Hospital16, University of California, Los Angeles17, University of Toronto18, University of Michigan19, University of Alberta20, Harvard University21, University of Colorado Denver22
TL;DR: This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.