The effect of New Zealand blackcurrant on sport performance and related biomarkers: a systematic review and meta-analysis.

BACKGROUND: Blackcurrants have come to be regarded as a superfood because of their high polyphenol content, namely anthocyanins. While many berry types have been studied, blackcurrant-anthocyanins may be the superior berry when it comes to athletic performance. The purpose of the review was to evaluate the effects of blackcurrant supplementation on athletic performance, oxidative markers, cognition, and side effects. METHODS: Systematic review and meta-analysis. Review manager software (version 5.3) was used for the meta-analysis. The risks of bias was independently assessed using the guidelines and criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The data sources for the search included MEDLINE (Ovid), Google Scholar databases, additional references lists, conference proceedings and grey literature until August 2019. Eligibility Criteria included all blackcurrant (New Zealand derived) interventions, randomised control trials, human participants, placebo-controlled only. RESULTS: A total of 16 separate studies met the criteria for inclusion in the systematic review, with 9 studies contributing to this sport performance meta-analysis. There was an improvement in sport performance when supplementing with blackcurrant, 0.45 (95% CI 0.09-0.81, p = 0.01). The effective dose appears to be between 105 and 210 mg of total blackcurrant anthocyanins, prior to exercise. There were insufficient studies reporting oxidative markers, cognitive effects or biomarkers, and/or side effects to comment on the mechanism of action. CONCLUSION: Blackcurrant has a small, but significant, effect on sport performance, with no known detrimental side effects.

Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lung inflammation and Trichuris Muris infection.

Glucocorticoids (Gcs) are widely prescribed anti-inflammatory compounds, which act through the glucocorticoid receptor (GR). Using an unbiased proteomics screen in lung tissue, we identified the membrane protein caveolin -1 (Cav1) as a direct interaction partner of the GR. In Cav1 knockout mice GR transactivates anti-inflammatory genes, including Dusp1, more than in controls. We therefore determined the role of Cav1 in modulating Gc action in two models of pulmonary inflammation. We first tested innate responses in lung. Loss of Cav1 impaired the inflammatory response to nebulized LPS, increasing cytokine/chemokine secretion from lung, but impairing neutrophil infiltration. Despite these changes to the inflammatory response, there was no Cav1 effect on anti-inflammatory capacity of Gcs. We also tested GR/Cav1 crosstalk in a model of allergic airway inflammation. Cav1 had a very mild effect on the inflammatory response, but no effect on the Gc response - with comparable immune cell infiltrate (macrophage, eosinophils, neutrophils), pathological score and PAS positive cells observed between both genotypes. Pursuing the Th2 adaptive immune response further we demonstrate that Cav1 knockout mice retained their ability to expel the intestinal nematode parasite T.muris, which requires adaptive Th2 immune response for elimination. Therefore, Cav1 regulates innate immune responses in the lung, but does not have an effect on Th2-mediated adaptive immunity in lung or gut. Although we demonstrate that Cav1 regulates GR transactivation of anti-inflammatory genes, this does not translate to an effect on suppression of inflammation in vivo.

Integrating Active Learning and Transfer Learning for Carotid Intima-Media Thickness Video Interpretation.

Cardiovascular disease (CVD) is the number one killer in the USA, yet it is largely preventable (World Health Organization 2011). To prevent CVD, carotid intima-media thickness (CIMT) imaging, a noninvasive ultrasonography method, has proven to be clinically valuable in identifying at-risk persons before adverse events. Researchers are developing systems to automate CIMT video interpretation based on deep learning, but such efforts are impeded by the lack of large annotated CIMT video datasets. CIMT video annotation is not only tedious, laborious, and time consuming, but also demanding of costly, specialty-oriented knowledge and skills, which are not easily accessible. To dramatically reduce the cost of CIMT video annotation, this paper makes three main contributions. Our first contribution is a new concept, called Annotation Unit (AU), which simplifies the entire CIMT video annotation process down to six simple mouse clicks. Our second contribution is a new algorithm, called AFT (active fine-tuning), which naturally integrates active learning and transfer learning (fine-tuning) into a single framework. AFT starts directly with a pre-trained convolutional neural network (CNN), focuses on selecting the most informative and representative AU s from the unannotated pool for annotation, and then fine-tunes the CNN by incorporating newly annotated AU s in each iteration to enhance the CNN's performance gradually. Our third contribution is a systematic evaluation, which shows that, in comparison with the state-of-the-art method (Tajbakhsh et al., IEEE Trans Med Imaging 35(5):1299-1312, 2016), our method can cut the annotation cost by >81% relative to their training from scratch and >50% relative to their random selection. This performance is attributed to the several advantages derived from the advanced active, continuous learning capability of our AFT method.

Transcriptome profiling of bovine ovarian theca cells treated with fibroblast growth factor 9.

We reported previously that fibroblast growth factor 9 (FGF9) acts as an antidifferentiation factor, stimulating proliferation of granulosa cells (GCs) and theca cells (TCs) while suppressing hormone-induced steroidogenesis of these cells. How FGF9 acts to simultaneously suppress steroidogenesis and stimulate proliferation remains to be fully elucidated. Thus, this study was undertaken to clarify the effects of FGF9 on the TC transcriptome. Ovaries were obtained from beef heifers at a local abattoir, TCs were isolated from large antral follicles, and cultured with or without 30 ng/mL of FGF9 for 24 h in the presence of LH and IGF-1. After treatment, total RNA was extracted from TC and processed for microarray using Affymetrix GeneChip Bovine Genome Arrays (n = 4/group). Transcriptome analysis comparing FGF9-treated TC with control TC using 1.3-fold cutoff, and a P < 0.05 significance level identified 355 differentially expressed transcripts, with 164 elements upregulated and 191 elements downregulated by FGF9. The ingenuity pathway analysis (IPA) was used to investigate how FGF9 treatment affects molecular pathways, biological functions, and the connection between molecules in bovine TC. The IPA software identified 346 pathways in response to FGF9 in TC involved in several biological functions and unveiled interesting relationships among genes related to cell proliferation (eg, CCND1, FZD5, and MYB), antioxidation/cytoprotection (eg, HMOX1 and NQO1), and steroidogenesis (eg, CYP11A1 and STAR). Overall, genes, pathways, and networks identified in this study painted a picture of how FGF9 may regulate folliculogenesis, providing novel candidate genes for further investigation of FGF9 functions in ovarian follicular development.

Endovascular treatment for acute basilar thrombosis via a transradial approach: Initial experience and future considerations.

Acute basilar artery occlusion (BAO) secondary to emergent large vessel occlusion (ELVO) has an extremely poor natural history, with a reported mortality rate up to 95%. Mechanical thrombectomy in the setting of ELVO is generally performed via a transfemoral approach. However, radial access is increasingly being utilized as an alternative. We report our initial multi-institutional experience using primary radial access in the treatment of acute BAO in nine consecutive cases. Technical success defined as a TICI score of 2B or 3 was achieved in 89% of cases. Average puncture to revascularization time was 35.8 minutes. There were no complications related to radial artery catheterization. We contend radial access should potentially be considered as the first-line approach given inherent advantages over femoral access for mechanical thrombectomy for BAO.

A reference genome for Nicotiana tabacum enables map-based cloning of homeologous loci implicated in nitrogen utilization efficiency.

BACKGROUND: Tobacco (Nicotiana tabacum) is an important plant model system that has played a key role in the early development of molecular plant biology. The tobacco genome is large and its characterisation challenging because it is an allotetraploid, likely arising from hybridisation between diploid N. sylvestris and N. tomentosiformis ancestors. A draft assembly was recently published for N. tabacum, but because of the aforementioned genome complexities it was of limited utility due to a high level of fragmentation. RESULTS: Here we report an improved tobacco genome assembly, which, aided by the application of optical mapping, achieves an N50 size of 2.17 Mb and enables anchoring of 64% of the genome to pseudomolecules; a significant increase from the previous value of 19%. We use this assembly to identify two homeologous genes that explain the differentiation of the burley tobacco market class, with potential for greater understanding of Nitrogen Utilization Efficiency and Nitrogen Use Efficiency in plants; an important trait for future sustainability of agricultural production. CONCLUSIONS: Development of an improved genome assembly for N. tabacum enables what we believe to be the first successful map-based gene discovery for the species, and demonstrates the value of an improved assembly for future research in this model and commercially-important species.

Convolutional Neural Networks for Medical Image Analysis: Full Training or Fine Tuning?

Training a deep convolutional neural network (CNN) from scratch is difficult because it requires a large amount of labeled training data and a great deal of expertise to ensure proper convergence. A promising alternative is to fine-tune a CNN that has been pre-trained using, for instance, a large set of labeled natural images. However, the substantial differences between natural and medical images may advise against such knowledge transfer. In this paper, we seek to answer the following central question in the context of medical image analysis: Can the use of pre-trained deep CNNs with sufficient fine-tuning eliminate the need for training a deep CNN from scratch? To address this question, we considered four distinct medical imaging applications in three specialties (radiology, cardiology, and gastroenterology) involving classification, detection, and segmentation from three different imaging modalities, and investigated how the performance of deep CNNs trained from scratch compared with the pre-trained CNNs fine-tuned in a layer-wise manner. Our experiments consistently demonstrated that 1) the use of a pre-trained CNN with adequate fine-tuning outperformed or, in the worst case, performed as well as a CNN trained from scratch; 2) fine-tuned CNNs were more robust to the size of training sets than CNNs trained from scratch; 3) neither shallow tuning nor deep tuning was the optimal choice for a particular application; and 4) our layer-wise fine-tuning scheme could offer a practical way to reach the best performance for the application at hand based on the amount of available data.

Hyperacute Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage typically occurs 3-14 days after aneurysm rupture. We describe a series of patients who developed vasospasm within minutes of aneurysm rupture. This phenomenon, which we term, "hyperacute vasospasm," has been reported in animal models of SAH, but hitherto has been poorly described in humans. METHODS: Eleven patients were identified from an institutional registry who had aneurysmal rupture during catheter cerebral angiography between 1997 and 2009. We quantified the degree of vasoconstriction using vascular diameter index (VDI). The change in VDI (delta VDI or DVDI) was calculated by determining the difference in VDI before and after the procedure. We also examined the relationship between hyperacute vasospasm and delayed cerebral ischemia. RESULTS: Ten of eleven (91%) patients with intraoperative aneurysm rupture had cerebral vasoconstriction within minutes of intra-procedural aneurysmal rupture. Six of eleven patients (55%) with hyperacute vasospasm developed delayed cerebral infarction. CONCLUSIONS: Hyperacute vasospasm is likely common in patients with intraoperative aneurysm rupture and may be an unrecognized element of the natural history of aneurysmal subarachnoid hemorrhage. In this limited series, there was an association between hyperacute vasospasm and delayed cerebral infarction.

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

Risk Stratification for Cardiovascular Disease in Women in the Primary Care Setting.

BACKGROUND: Traditional risk assessment tools classify the majority of middle-aged women at low risk despite cardiovascular (CV) disease's affecting >50% of women and remaining the leading cause of death. Ultrasound-determined carotid intima-media thickness (CIMT) and/or computed tomographic coronary artery calcium score (CACS) quantify subclinical atherosclerosis and add incremental prognostic value. The aim of this study was to assess the utility of CIMT and CACS to detect subclinical atherosclerosis in younger women. METHODS: Asymptomatic women aged 50 to 65 years with at least one CV risk factor and low Framingham risk scores were identified prospectively at primary care and cardiology clinics. Mean intimal thickness, plaque on CIMT, and Agatston calcium score for CACS were obtained. RESULTS: Of 86 women (mean age, 58 ± 4.6 years; mean Framingham risk score, 1.9 ± 1.2; mean low-density lipoprotein cholesterol level, 138.9 ± 37.0 mg/dL), 53 (62%) had high-risk CIMT (51% plaque, 11% CIMT > 75th percentile). In contrast, three women (3.5%) had CACS > 100, all of whom had plaque by CIMT. Of the 58 women with CACS of 0, 32 (55%) had high-risk CIMT (48% plaque, 7% CIMT > 75th percentile). CONCLUSIONS: In patients referred by their physicians for assessment of CV risk, CIMT in asymptomatic middle-aged women with at least one CV risk factor and low risk by the Framingham risk score identified a large number with advanced subclinical atherosclerosis despite low CACS. Our results suggest that CIMT may be a more sensitive method for CV risk assessment than CACS or traditional risk tools in this population. Further studies are needed to determine if earlier detection would be of clinical benefit.

Assessment of colon and bladder crosstalk in an experimental colitis model using contrast-enhanced magnetic resonance imaging.

BACKGROUND: Inflammatory bowel disease (IBD) consists of two chronic remitting-relapsing inflammatory disorders in the colon referred to as ulcerative colitis and Crohn's disease (CD). Inflammatory bowel disease affects about 1.4 million Americans. 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis is a widely used model of experimental intestinal inflammation with characteristic transmural and segmental lesions that are similar to CD. METHODS: Here, we report on the use of contrast-enhanced magnetic resonance imaging (CE-MRI) to monitor in vivo bladder permeability changes resulting from bladder crosstalk following colon TNBS exposure, and TNBS-induced colitis. Changes in MRI signal intensities and histology were evaluated for both colon and bladder regions. KEY RESULTS: Uptake of contrast agent in the colon demonstrated a significant increase in signal intensity (SI) for TNBS-exposed rats (p < 0.01) compared to controls. In addition, a significant increase in bladder SI for colon TNBS-exposed rats (p < 0.001) was observed compared to saline controls. Histological damage within the colon was observed, however, bladder histology indicated a normal urothelium in rats with TNBS-induced colitis, despite increased permeability seen by CE-MRI. CONCLUSIONS & INFERENCES: Contrast-enhanced MRI was able to quantitatively measure inflammation associated with TNBS-induced colitis, and assess bladder crosstalk measured as an increase in urothelial permeability. Although CE-MRI is routinely used to assess inflammation with IBD, currently there is no diagnostic test to assess bladder crosstalk with this disease, and our developed method may be useful in providing crosstalk information between organ and tissue systems in IBD patients, in addition to colitis.

A perspective on the New American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment.

The recently published American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for cardiovascular risk assessment provide equations to estimate the 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk in African Americans and non-Hispanic whites, include stroke as an adverse cardiovascular outcome, and emphasize shared decision making. The guidelines provide a valuable framework that can be adapted on the basis of clinical judgment and individual/institutional expertise. In this review, we provide a perspective on the new guidelines, highlighting what is new, what is controversial, and potential adaptations. We recommend obtaining family history of ASCVD at the time of estimating ASCVD risk and consideration of imaging to assess subclinical disease burden in patients at intermediate risk. In addition to the adjuncts for ASCVD risk estimation recommended in the guidelines, measures that may be useful in refining risk estimates include carotid ultrasonography, aortic pulse wave velocity, and serum lipoprotein(a) levels. Finally, we stress the need for research efforts to improve assessment of ASCVD risk given the suboptimal performance of available risk algorithms and suggest potential future directions in this regard.

A summary and critical assessment of the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: filling the gaps.

The American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines has recently released the new cholesterol treatment guideline. This update was based on a systematic review of the evidence and replaces the previous guidelines from 2002 that were widely accepted and implemented in clinical practice. The new cholesterol treatment guideline emphasizes matching the intensity of statin treatment to the level of atherosclerotic cardiovascular disease (ASCVD) risk and replaces the old paradigm of pursuing low-density lipoprotein cholesterol targets. The new guideline also emphasizes the primacy of the evidence base for statin therapy for ASCVD risk reduction and lists several patient groups that will not benefit from statin treatment despite their high cardiovascular risk, such as those with heart failure (New York Heart Association class II-IV) and patients undergoing hemodialysis. The guideline has been received with mixed reviews and significant controversy. Because of the evidence-based nature of the guideline, there is room for several questions and uncertainties on when and how to use lipid-lowering therapy in clinical practice. The goal of the Mayo Clinic Task Force in the assessment, interpretation, and expansion of the ACC/AHA cholesterol treatment guideline is to address gaps in information and some of the controversial aspects of the newly released cholesterol management guideline using additional sources of evidence and expert opinion as needed to guide clinicians on key aspects of ASCVD risk reduction.

Two cases of apical ballooning syndrome masking apical hypertrophic cardiomyopathy.

Apical akinesis and dilation in the absence of obstructive coronary artery disease is a typical feature of stress-induced (takotsubo) cardiomyopathy, whereas apical hypertrophy is seen in apical-variant hypertrophic cardiomyopathy. We report the cases of 2 patients who presented with takotsubo cardiomyopathy and were subsequently found to have apical-variant hypertrophic cardiomyopathy, after the apical ballooning from the takotsubo cardiomyopathy had resolved. The first patient, a 43-year-old woman with a history of alcohol abuse, presented with shortness of breath, electrocardiographic and echocardiographic features consistent with takotsubo cardiomyopathy, and no significant coronary artery disease. An echocardiogram 2 weeks later revealed a normal left ventricular ejection fraction and newly apparent apical hypertrophy. The 2nd patient, a 70-year-old woman with pancreatitis, presented with chest pain, apical akinesis, and a left ventricular ejection fraction of 0.39, consistent with takotsubo cardiomyopathy. One month later, her left ventricular ejection fraction was normal; however, hypertrophy of the left ventricular apex was newly noted. To our knowledge, these are the first reported cases in which apical-variant hypertrophic cardiomyopathy was masked by apical ballooning from stress-induced cardiomyopathy.

The protection of bovine skeletal myofibrils from proteolytic damage post mortem by small heat shock proteins.

This study aimed to determine how small heat shock proteins (sHSPs) protect myofibrillar proteins from µ-calpain degradation during ageing. Immunoprecipitation experiments with M. longissimus dorsi (LD) from Angus heifers (n = 14) examined the interaction between αß-crystallin, desmin, titin, HSP20, HSP27 and µ-calpain. Results showed that αß-crystallin associated with desmin, titin, HSP20, HSP27 and µ-calpain. Exogenous αß-crystallin reduced desmin and titin degradations in myofibrillar extracts and attenuated µ-calpain activity. In a second experiment, bull LD (n = 94) were aged at -1.5°C for up to 28 days post mortem. µ-Calpain autolysed faster in high ultimate pH (pH(u)) meat (pH(u)≥6.2) and this was concomitant with the more rapid degradation of titin and filamin in this pH(u) group. Desmin stability in intermediate pH(u) meat (pH(u) 5.8 to 6.19) may be due to the protection of myofibril-bound sHSPs combined with the competitive inhibition of µ-calpain by sHSPs.

The retinoic acid-producing capacity of gut dendritic cells and macrophages is reduced during persistent T. muris infection.

Trichuris muris is an intestinal nematode that invades the colonic epithelium triggering a mucosal inflammation. Vitamin A and its active metabolite retinoic acid are strongly linked with the modulation of gut immune responses. Here, we describe the temporal changes in the expression of aldehyde dehydrogenase (ALDH) enzymes, responsible for converting dietary-absorbed vitamin A into the immuno-modulatory retinoic acid in lamina propria leucocytes post-infection. We show that ALDH enzymes are expressed by both colonic macrophages and dendritic cells. Further, during an on-going T. muris infection, ALDH expression is repressed from uninfected levels and only recovers to normal levels following expulsion of the parasite. These results suggest that local regulation of cellular levels of retinoic acid is an important component of infection-driven inflammation.

Echocardiographic measures of myocardial deformation by speckle-tracking technologies: the need for standardization?

BACKGROUND: Multiple vendor-specific two-dimensional speckle-tracking echocardiographic algorithms with which to characterize myocardial mechanics are commercially available. The purpose of this study was to compare global longitudinal strain (GLS) results between two independent software vendors using a neutral image platform. METHODS: A convenience sample of 100 prospectively collected patients was evaluated. Subjects with more than two left ventricular endocardial segments poorly delineated were excluded. GLS was obtained from the apical four-chamber, three-chamber, and two-chamber views using two independent speckle-tracking echocardiographic software packages (EchoInsight version 1.5.0 and Image-Arena version 4.5). Linear regression analysis and paired t tests were used to compare GLS results. Intraclass correlation coefficients and Bland-Altman plots were used for assessments of reliability. RESULTS: The "out-of-the-box" mean GLS was -12.99 ± 2.38% using EchoInsight and -16.87 ± 2.84% using Image-Arena (mean difference, 3.87 ± 2.42%; P = .0001). Agreement between the software packages was moderate (intraclass correlation coefficient, 0.43; 95% confidence interval, 0.32-0.55). Using uniform variables to derive GLS (Lagrangian strain measured in systole and diastole at the endocardium and averaging the peak segmental strain curves), EchoInsight GLS was -16.17 ± 2.90% and Image-Arena GLS was -16.87 ± 2.84% (mean difference, 0.70 ± 2.75%; P = .02), with an intraclass correlation coefficient of 0.70 (95% confidence interval, 0.52-0.79). CONCLUSIONS: Image-Arena GLS results were consistently different (more negative) than EchoInsight measures out of the box but became similar when information used to derive GLS was uniform. The evolution of measures of myocardial mechanics into routine clinical practice will require vigilance and standardization of the various techniques, necessitating independent validation of commercially available speckle-tracking echocardiographic products.