In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in ...the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided.
Subsequent independent guideline groups, including the 2014 Joint British Societies Consensus Recommendations for the Prevention of Cardiovascular Disease (JBS3) (3), the 2014 Veterans' ...Administration/Department of Defense Guidelines on Management of Dyslipidemia (4), and the recent U.S. Preventive Services Task Force draft recommendations (5), have used similar, rigorous approaches to reviewing and synthesizing evidence, resulting in similar treatment recommendations.\n Joseph Butterfield Chair in Pediatrics Sanofi-Aventis None None None None None Scott M. Grundy Content Reviewer--Chair, Update to ACC/AHA Cholesterol Guideline University of Texas Southwestern Medical Center at Dallas--Professor of Internal Medicine None None None None None None James L. Januzzi Content Reviewer--Chair, ACC Task Force on Clinical Expert Consensus Documents Massachusetts General Hospital--Director, Dennis and Marilyn Barry Fellowship in Cardiology Research Cardiology Division; Harvard Medical School--Hutter Family Professor of Medicine Novartislow * Rochelow * None None Amgen (DSMB) None None Joseph J. Saseen Content Reviewer--Cardiovascular Team Council University of Colorado Anschutz Medical Campus --Professor and Vice Chair, Department of Clinical Pharmacy, Professor, Department of Family Medicine None None None None None None Michael D. Shapiro Content Reviewer--Prevention Council Oregon Health & Science University--Associate Professor of Medicine and RadiologyDirector, Cardiac MR CT ProgramCenter for Preventive CardiologyKnight Cardiovascular Institute None None None Amarindagger Amgendagger Isisdagger Sanofidagger Synagevadagger None None Barbara S. Wiggins Content Reviewer--ACC Task Force on Clinical Expert Consensus Documents Medical University of South Carolina--Clinical Pharmacy Specialist Cardiology, Department of Pharmacy Services None None None None None None black square This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant to this document.
Soy protein isolate (SPI) powders often have poor water solubility, particularly at pH values close to neutral, which is an attribute that is an issue for its incorporation into complex nutritional ...systems. Therefore, the objective of this study was to improve SPI solubility while maintaining low viscosity. Thus, the intention was to examine the solubility and rheological properties of a commercial SPI powder at pH values of 2.0, 6.9, and 9.0, and determine if heat treatment at acidic or alkaline conditions might positively influence protein solubility, once re-adjusted back to pH 6.9. Adjusting the pH of SPI dispersions from pH 6.9 to 2.0 or 9.0 led to an increase in protein solubility with a concomitant increase in viscosity at 20 °C. Meanwhile, heat treatment at 90 °C significantly improved the solubility at all pH values and resulted in a decrease in viscosity in samples heated at pH 9.0. All SPI dispersions measured under low-amplitude rheological conditions showed elastic-like behaviour (i.e., G′ > G″), indicating a weak “gel-like” structure at frequencies less than 10 Hz. In summary, the physical properties of SPI can be manipulated through heat treatment under acidic or alkaline conditions when the protein subunits are dissociated, before re-adjusting to pH 6.9.
This study investigated some biofunctional, structural, and tribological attributes of synbiotic yoghurts produced using Lacticaseibacillus paracasei as probiotic, and galactofructose, inulin, soy ...protein isolate, and spirulina as prebiotics. The highest gamma-aminobutyric acid (GABA) production (99.63 μg mL−1) and glutamic acid consumption (98.39 μg mL−1) was found in spirulina-supplemented probiotic yoghurts (YSP), followed by galactofructose-supplemented probiotic yoghurts (YGF). However, YSP exhibited the lowest probiotic viability and the greatest pH drop. The biological activity of YSP, in terms of total phenolics, antioxidant potential, antihypertensive activity, and degree of hydrolysis was significantly higher than the other yoghurts. YSP showed lower friction coefficient in the high sliding velocities compared with other yoghurt samples. The best appearance and mouthfeel was rated by panellists for YSP, while the taste, texture, and overall acceptance of other yoghurts were preferred. Overall, the synbiotic yoghurts containing spirulina, and galactofructose represent a promising strategy for development of functional dairy products.
An investigation on the impacts of different prebiotics (inulin, galactofructose, soy protein isolate (SPI), and spirulina) and co-culturing with Lacticaseibacillus paracasei on the biological ...metabolites free amino acids (FAAs), free fatty acids (FFAs), and organic acids and stability parameters of fermented milk is presented. All fermented milks represented an increased FAA content compared with their milk counterparts, while the synbiotic fermented milk supplemented with galactofructose (YGF) and spirulina (YSP) were more efficient in this regard. The total organic acid content of the samples was not significantly affected by the type of prebiotics, and co-culturing by L.paracasei, YGF and YSP presented a different pattern, with the highest succinic acid (0.77 mm) and oxoglutaric acid (0.27 mm) contents, respectively. The thermal stability of the fermented milks did not change by loading various prebiotics and co-culturing, while the phase, colloidal, mechanical, and shear stability indexes were significantly affected.
Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we ...describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
Chronic kidney disease (CKD) is associated with worse survival in patients with heart disease including those with implantable devices. Cardiac resynchronization therapy (CRT) can potentially improve ...renal function. To assess the relation between the change in renal function and survival with CRT, 238 patients undergoing initial CRT with defibrillator implantation between 2002 and 2011 were followed. The primary end point was all-cause mortality. The estimated glomerular filtration rate (eGFR), before implantation and 6 ± 3 months after CRT was calculated. Patients were grouped at baseline into mild (stage I/II) or advanced (stage III/IV) CKD. Patients with end-stage renal disease were excluded. The mean follow-up time was 4.3 years. Multivariate analysis of baseline clinical characteristics showed that only renal function predicted the change in eGFR over the first 6 months of CRT. In the subgroup with mild CKD, eGFR decreased (78.5 ± 17.3 to 67.8 ± 26.8 p <0.001), whereas eGFR did not change in the subgroup with advanced CKD (45.6 ± 11.1 to 46.8 ± 17.0, p = 0.46). Patients with advanced CKD had higher mortality than those with mild CKD (p <0.002). In both subgroups, an increase in eGFR was associated with improved survival (hazard ratio = 0.79, p <0.001). In conclusion, baseline renal function and the subsequent change in eGFR are associated with long-term survival with CRT.
Background
Cardiac resynchronization therapy (CRT) improves functional status, reduces heart failure hospitalizations, and decreases mortality. Several comorbidities including renal function affect ...outcomes with CRT. However, moderate to severe chronic kidney disease (CKD) was an exclusion criterion in the large randomized control trials.
Objective
To evaluate the association of renal function on survival following CRT implantation.
Methods
This was a retrospective analysis of 432 consecutive patients implanted with an implantable cardioverter defibrillator with CRT (CRT‐D). The primary end point was defined as death by any cause, and it was determined using hospital records and the U.S. Social Security Death Index. A Kaplan‐Meier analysis was performed separating renal dysfunction into renal stage based on glomerular filtration rate. Multivariate analysis was performed to assess the clinical predictors of mortality.
Results
Patients were followed for up to 12 years with a mean follow‐up time of 4.3 ± 3.2 years. A total of 164 patients (39.3%) died over the course of the study. Patients with normal and mild renal diseases (Stages 1 and 2) had improved survival compared with those with moderate‐, severe‐, or end‐stage (Stages 3–5) renal disease. This effect remained statistically significant after multivariate analysis. The estimated 5‐year mortality was 36.3% for stage 1, 33.4% for stage 2, 40.6% for stage 3, and 62.1% for stage 4/5 kidney disease (P = 0.004 by log‐rank test).
Conclusion
CKD is a strong and an independent predictor of long‐term mortality among patients undergoing CRT‐D implantation.
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