Summary Background Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are ...modified by diabetes is unknown. Methods We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. Findings We analysed data for 1 024 977 participants (128 505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75 306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21 237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2–1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m2 vs 95 mL/min per 1·73 m2 , HR 1·35; 95% CI 1·18–1·55; vs 1·33; 1·19–1·48 and at ACR 30 mg/g vs 5 mg/g, 1·50; 1·35–1·65 vs 1·52; 1·38–1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. Interpretation Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. Funding US National Kidney Foundation.
DNA sequencing has identified recurrent mutations that drive the aggressiveness of prostate cancers. Surprisingly, the influence of genomic, epigenomic, and transcriptomic dysregulation on the tumor ...proteome remains poorly understood. We profiled the genomes, epigenomes, transcriptomes, and proteomes of 76 localized, intermediate-risk prostate cancers. We discovered that the genomic subtypes of prostate cancer converge on five proteomic subtypes, with distinct clinical trajectories. ETS fusions, the most common alteration in prostate tumors, affect different genes and pathways in the proteome and transcriptome. Globally, mRNA abundance changes explain only ∼10% of protein abundance variability. As a result, prognostic biomarkers combining genomic or epigenomic features with proteomic ones significantly outperform biomarkers comprised of a single data type.
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•A comprehensive proteomic analyses of localized prostate cancers•Integration of all levels of the central dogma (DNA → RNA → protein)•ETS fusions have divergent effects on transcriptome and proteome•Combining genomics and proteomics improves biomarker performance
Sinha et al. determine the proteogenomic landscape of localized, intermediate-risk prostate cancers and show that the presence of ETS gene fusions has one of the strongest effects on the proteome. Prognostic biomarkers that integrate multi-omics significantly outperform those comprised of a single data type.
•Kinetic and microscopic study showing how barley protein affects starch degradation.•Protein inhibits enzymatic degradation through several mechanisms.•Protein-enzyme binding interaction is the main ...reason.
The conversion of barley starch to sugars is a complex enzymic process. Most previous work concerned the biotechnical aspect of in situ barley enzymes. However, the interactions among the macromolecular substrates and their effects on enzymic catalysis has been little examined. Here, we explore the mechanisms whereby interactions of protein and starch in barley flour affect the kinetics of enzymatic hydrolysis of starch in an in vitro system, using digestion rate data and structural analysis by confocal microscopy. The degradation kinetics of both uncooked barley flour and of purified starches are found to be two-step sequential processes. Barley proteins, especially the water-soluble component, are found to retard the digestion of starch degraded by α-amylase: the enzyme binds with water-insoluble protein and with starch granules, leading to reduced starch hydrolysis. These findings are of potential industrial value in both the brewing and food industries.
The majority of newly diagnosed prostate cancers are slow growing, with a long natural life history. Yet a subset can metastasize with lethal consequences. We reconstructed the phylogenies of 293 ...localized prostate tumors linked to clinical outcome data. Multiple subclones were detected in 59% of patients, and specific subclonal architectures associate with adverse clinicopathological features. Early tumor development is characterized by point mutations and deletions followed by later subclonal amplifications and changes in trinucleotide mutational signatures. Specific genes are selectively mutated prior to or following subclonal diversification, including MTOR, NKX3-1, and RB1. Patients with low-risk monoclonal tumors rarely relapse after primary therapy (7%), while those with high-risk polyclonal tumors frequently do (61%). The presence of multiple subclones in an index biopsy may be necessary, but not sufficient, for relapse of localized prostate cancer, suggesting that evolution-aware biomarkers should be studied in prospective studies of low-risk tumors suitable for active surveillance.
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•The phylogenies of 293 localized prostate cancers were reconstructed•Multiple subclones were detected in 59% of patients•Specific genes are selectively mutated early or late in tumor evolution•Subclonal architecture adds prognostic ability to previously developed biomarkers
Tumors evolve during their natural life history. We studied the evolution of newly diagnosed prostate tumors and identified specific genes mutated early or late in a tumor’s life history. Considering subclonality improved predictions of disease aggressivity, identifying those patients who might be good candidates for receiving less treatment.
Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is ...to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus.
Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is ...to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus.
Molecular structure of whole and debranched barley starch has been characterized.Correlations found between protein content, starch molecular structure & grain size.Starch structure offers an ...improved way to choose grains for brewing quality.Target functional properties include more fermentable sugars, less limit dextrins.
Correlations among barley protein, starch molecular structure and grain size were determined using 30 barley samples with variable protein contents. Starch molecular structure was characterized by fluorophore-assisted carbohydrate electrophoresis and by size-exclusion chromatography (SEC, also termed GPC). The chain-length distributions of amylopectin were fitted using a mathematical model reflecting the relative activities of starch branching enzymes and starch synthase enzymes. Increased protein content significantly and negatively correlated with higher amounts of amylose with longer chains (degree of polymerization, DP 1600⿿40000) while barley grain sizes positively associated with starch contents. Protein content also positively correlated with the proportion of longer chains of amylopectin (DP 34⿿100). These results showed that the enzyme activities of starch synthases change with protein content, leading to altered starch contents, structures and grain sizes. From this perspective, selecting for large grain size (or low protein content) does not necessarily relate to starch structure, although may suggest long chains of amylopectin. Measuring starch structure could give a good indication of process performance in human food, animal feed and brewing, as all these structural features contribute to significant functional properties.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A ...systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.
•Barley starch structural changes during malting are investigated.•Both starch amylose and amylopectin are hydrolyzed during malting.•Protein retards starch hydrolysis in mashing by inhibiting ...granule swelling.•Barleys with more short-chain amylose molecules release more fermentable sugars.•Starch molecular structure is useful for determining fermentable sugars production.
Ten barley samples containing varied protein contents were subject to malting followed by mashing to investigate molecular effects of both barley starch and starch- protein interactions on malting and mashing performances, and the underlying mechanism. Starch granular changes were examined using differential scanning calorimetry and scanning electron microscopy. The molecular fine structures of amylose and amylopectin from unmalted and malted grain were obtained using size-exclusion chromatography. The results showed that both amylose and amylopectin polymers were hydrolyzed at the same time during malting. Protein and amylose content in both unmalted and malted barley significant negatively correlated with fermentable sugar content after mashing. While protein content is currently the main criterion for choosing malting varieties, this study shows that information about starch molecular structure is also useful for determining the release of fermentable sugars, an important functional property. This provides brewers with some new methods to choose malting barley.
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