Radiomics Studies on Ischemic Stroke and Carotid Atherosclerotic Disease: A Reporting Quality Assessment.

Objective: To assess the reporting quality of radiomics studies on ischemic stroke, intracranial and carotid atherosclerotic disease using the Image Biomarker Standardization Initiative (IBSI) reporting guidelines with the aim of finding avenues of improvement for future publications. Method: PubMed database was searched to identify relevant radiomics studies. Of 560 articles, 41 original research articles were included in this analysis. Based on IBSI radiomics reporting guidelines, checklists for CT-based and MRI-based studies were created to allow a structured and comprehensive evaluation of each study's adherence to these guidelines. Results: The main topics covered by the included radiomics studies were ischemic stroke, intracranial artery disease, and carotid atherosclerotic disease. The reporting checklist median score was 17/40 for the 20 CT-based radiomics studies and 22.5/50 for the 20 MRI-based studies. Basic items like imaging modality, region of interest, and image biomarker set utilized were included in all studies. However, details regarding image acquisition and reconstruction, post-acquisition image processing, and image biomarkers computation were inconsistently detailed across studies. Conclusion: The overall reporting quality of the included radiomics studies was suboptimal. These findings underscore a pressing need for improved reporting practices in radiomics research, to ensure validation and reproducibility of results. Our study provides insights into current reporting standards and highlights specific areas where adherence to IBSI guidelines could be significantly improved.

Established and potential cardiovascular risk factors in metabolic syndrome: Effect of bariatric surgery.

PURPOSE OF REVIEW: The aim of this review was to provide an overview of the role of novel biomarkers in metabolic syndrome, their association with cardiovascular risk and the impact of bariatric surgery on these biomarkers. RECENT FINDINGS: Metabolic syndrome encompasses an intricate network of health problems, and its constituents extend beyond the components of its operational definition. Obesity-related dyslipidaemia not only leads to quantitative changes in lipoprotein concentration but also alteration in qualitative composition of various lipoprotein subfractions, including HDL particles, rendering them proatherogenic. This is compounded by the concurrent existence of obstructive sleep apnoea (OSA) and nonalcoholic fatty liver disease (NAFLD), which pave the common pathway to inflammation and oxidative stress culminating in heightened atherosclerotic cardiovascular disease (ASCVD) risk. Bariatric surgery is an exceptional modality to reverse both conventional and less recognised aspects of metabolic syndrome. It reduces the burden of atherosclerosis by ameliorating the impact of obesity and its related complications (OSA, NAFLD) on quantitative and qualitative composition of lipoproteins, ultimately improving endothelial function and cardiovascular morbidity and mortality. SUMMARY: Several novel biomarkers, which are not traditionally considered as components of metabolic syndrome play a crucial role in determining ASCVD risk in metabolic syndrome. Due to their independent association with ASCVD, it is imperative that these are addressed. Bariatric surgery is a widely recognized intervention to improve the conventional risk factors associated with metabolic syndrome; however, it also serves as an effective treatment to optimize novel biomarkers.

Current appraises of therapeutic applications of nanocurcumin: A novel drug delivery approach for biomaterials in dentistry.

Curcumin is a natural herb and polyphenol that is obtained from the medicinal plant Curcuma longa. It's anti-bacterial, anti-inflammatory, anti-cancer, anti-mutagenic, antioxidant and antifungal properties can be leveraged to treat a myriad of oral and systemic diseases. However, natural curcumin has weak solubility, limited bioavailability and undergoes rapid degradation, which severely limits its therapeutic potential. To overcome these drawbacks, nanocurcumin (nCur) formulations have been developed for improved biomaterial delivery and enhanced treatment outcomes. This novel biomaterial holds tremendous promise for the treatment of various oral diseases, the majority of which are caused by dental biofilm. These include dental caries, periodontal disease, root canal infection and peri-implant diseases, as well as other non-biofilm mediated oral diseases such as oral cancer and oral lichen planus. A number of in-vitro studies have demonstrated the antibacterial efficacy of nCur in various formulations against common oral pathogens such as S. mutans, P. gingivalis and E. faecalis, which are strongly associated with dental caries, periodontitis and root canal infection, respectively. In addition, some clinical studies were suggestive of the notion that nCur can indeed enhance the clinical outcomes of oral diseases such as periodontitis and oral lichen planus, but the level of evidence was very low due to the small number of studies and the methodological limitations of the available studies. The versatility of nCur to treat a diverse range of oral diseases augurs well for its future in dentistry, as reflected by rapid pace in which studies pertaining to this topic are published in the scientific literature. In order to keep abreast of the latest development of nCur in dentistry, this narrative review was undertaken. The aim of this narrative review is to provide a contemporaneous update of the chemistry, properties, mechanism of action, and scientific evidence behind the usage of nCur in dentistry.

Coronary Angiography Complicated by Acute Ischaemic Stroke and the Use of Thrombolysis: a Cardiology Perspective and Narrative Review of Current Literature.

PURPOSE OF REVIEW: Coronary angiography-associated acute ischaemic stroke (CAAIS) is an uncommon event but is associated with significant mortality and morbidity. The incidence of CAAIS has increased with a rise in the volume of coronary angiography (CA) and percutaneous coronary intervention (PCI) performed. Intravenous thrombolysis (IVT) is utilized in the general management of acute ischaemic stroke; however, it is associated with a higher risk of intracranial hemorrhage (ICH). As CA or PCI is performed more often in an aging population or high-risk patients that also carry an increased risk of ICH, it is vital to minimize additional complications from the treatment of CAAIS. This article aims to review the pathophysiological mechanisms for CAAIS, clarify the current evidence regarding IVT use in this setting, and thus assist cardiologists in the management of CAAIS. RECENT FINDINGS: The pathophysiology for CAAIS may be different from acute ischaemic stroke in the general population. Embolic phenomena from dislodgement of calcium or other debris during manipulation of instrumentation during CA or PCI are likely mechanisms. This may contribute to altered thrombus composition, which affects the efficacy of IVT as suggested in recent studies. Furthermore, IVT in the management of CAAIS has not been evaluated specifically. The utilization of IVT should be carefully considered in CAAIS given a paucity of evidence demonstrating safety and efficacy in this setting. A multidisciplinary pathway that emphasizes the involvement of cardiologists in the treatment decision-making process would aid in thoughtful risk-benefit evaluation for IVT use in CAAIS and reduce adverse patient outcomes. Future studies to assess the impact of this pathway on CAAIS outcomes would be beneficial.

The impact of atherosclerotic cardiovascular disease, dyslipidaemia and lipid lowering therapy on Coronavirus disease 2019 outcomes: an examination of the available evidence.

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.

High density lipoprotein-associated miRNA is increased following Roux-en-Y gastric bypass surgery for severe obesity.

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affect circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDLs were isolated from patients with severe obesity (n = 53) before and 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDLs were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222, and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222, and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222, and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase activity were increased and intercellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with an increase in cholesterol efflux capacity (r = 0.326, P = 0.027 and r = 0.349, P = 0.017, respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy participants versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.

Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity.

INTRODUCTION: Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. METHODS: Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. RESULTS: Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04). CONCLUSION: Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

Local and Systemic Expression Profile of IL-10, IL-17, IL-27, IL-35, and IL-37 in Periodontal Diseases: A Cross-sectional Study.

AIM: This study aimed to compare the level of interleukin (IL)-10, IL-17, IL-27, IL-35, and IL-37 in the gingival crevicular fluid (GCF) and human plasma of subjects with periodontal disease. MATERIALS AND METHODS: In this cross-sectional study conducted over a 3-month period at a primary dental clinic in Malaysia, 45 participants were recruited via consecutive sampling and assigned into three groups, namely healthy periodontium group (n = 15), gingivitis group (n = 15), and periodontitis group (n = 15). Gingival crevicular fluid and plasma samples were collected from each participant. Enzyme-linked immunosorbent assay test was conducted to measure the concentration of IL-10, IL-17, IL-27, IL-35, and IL-37. Kruskal-Wallis H test was used to compare the interleukin levels between patient groups. RESULTS: In GCF samples, IL-17 level was the highest in the periodontitis group (p <0.05), while IL-27 was the lowest (p <0.05). Meanwhile, plasma levels of IL-27 and IL-37 were significantly lower (p <0.05) in the periodontitis group, but plasma IL-35 levels were observed to rise with increasing disease severity. CONCLUSION: There are reduced local and systemic levels of IL-27 in periodontitis patients. CLINICAL SIGNIFICANCE: Periodontal diseases exert both local and systemic effects, resulting in the destruction of the tooth-supporting structures and contributing to the systemic inflammatory burden. Some of the cytokines that were investigated in the current study, IL-17, IL-27, IL-35, and IL-37, can be potential biomarkers that warrant further longitudinal clinical studies to determine their usefulness as prognostic/diagnostic markers.

Metabolic and cardiovascular outcomes of bariatric surgery.

PURPOSE OF REVIEW: Bariatric surgery is an effective therapy for morbid obesity that also improves weight-related metabolic parameters and reduces morbidity and mortality. The purpose of this review is to consolidate our current understanding of metabolic, macrovascular and microvascular benefits of bariatric surgery and to provide an update. RECENT FINDINGS: Early resolution of insulin resistance and type 2 diabetes mellitus (T2DM) varies by type of bariatric surgery and appears to be mediated by changes in secretion of gut hormones, metabolism of bile acids, expression of glucose transporters and the gut microbiome. Dyslipidaemia, atherosclerosis, microvascular complications of obesity and diabetes, systemic and tissue-level inflammation show evidence of regression and hypertension improves significantly after bariatric surgery. SUMMARY: Bariatric surgery leads to improvements in obesity-related metabolic comorbidities such as dyslipidaemia, HDL functionality, hypertension, T2DM, insulin resistance and inflammation. It slows the atherosclerotic process and reduces cardiovascular and all-cause mortality. Recent data have demonstrated regression of the microvascular complications of obesity and diabetes including the regeneration of small nerve fibres. The magnitude of change in short-term metabolic effects depends on the surgical procedure whilst longer term effects are related to the amount of sustained excess weight loss.

EpiMOLAS: an intuitive web-based framework for genome-wide DNA methylation analysis.

BACKGROUND: DNA methylation is a crucial epigenomic mechanism in various biological processes. Using whole-genome bisulfite sequencing (WGBS) technology, methylated cytosine sites can be revealed at the single nucleotide level. However, the WGBS data analysis process is usually complicated and challenging. RESULTS: To alleviate the associated difficulties, we integrated the WGBS data processing steps and downstream analysis into a two-phase approach. First, we set up the required tools in Galaxy and developed workflows to calculate the methylation level from raw WGBS data and generate a methylation status summary, the mtable. This computation environment is wrapped into the Docker container image DocMethyl, which allows users to rapidly deploy an executable environment without tedious software installation and library dependency problems. Next, the mtable files were uploaded to the web server EpiMOLAS_web to link with the gene annotation databases that enable rapid data retrieval and analyses. CONCLUSION: To our knowledge, the EpiMOLAS framework, consisting of DocMethyl and EpiMOLAS_web, is the first approach to include containerization technology and a web-based system for WGBS data analysis from raw data processing to downstream analysis. EpiMOLAS will help users cope with their WGBS data and also conduct reproducible analyses of publicly available data, thereby gaining insights into the mechanisms underlying complex biological phenomenon. The Galaxy Docker image DocMethyl is available at https://hub.docker.com/r/lsbnb/docmethyl/. EpiMOLAS_web is publicly accessible at http://symbiosis.iis.sinica.edu.tw/epimolas/.

Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes.

AIMS: The aim of this study was to evaluate the contribution of small and large fibre neuropathy to erectile dysfunction (ED) in men with type 2 diabetes (T2D). METHODS: Measures of small and large fibre neuropathy were evaluated in 49 participants with T2D and 20 age-matched controls. RESULTS: ED was present in 59% of participants with T2D. There was no difference in age, duration of diabetes, blood pressure, lipid profile, vibration perception threshold (V) (14.3 ± 7.8 vs 11.2 ± 6.6, P = .429), peroneal (41.4 ± 8.2 vs 44.8 ± 4.4, P = .10) and sural (45.4 ± 5.6 vs 47.1 ± 5.8) nerve conduction velocities (m/s), cold (25.1 ± 3.8 vs 26.2 ± 2.9, P = .815) and warm (43.2 ± 4.0 vs 41.0 ± 3.8) perception thresholds (°C), and deep breathing heart rate variability (18 ± 8 vs 18 ± 8) between participants with and without ED. However, intraepidermal nerve fibre density (no./mm2 ) (4.6 ± 2.8 vs 13.7 ± 2.7, P < .001), corneal nerve fibre density (no./mm2 ) (23.5 ± 6.8 vs 31.3 ± 8.2, P < .001), corneal nerve fibre branch density (no./mm2 ) (55.4 ± 35.3 vs 97.7 ± 46.4, P = .004), corneal nerve fibre length (mm/mm2 ) (17.6 ± 6.8 vs 27.3 ± 6.8, P < .001), and sural (7.7 ± 6.1 vs 14.6 ± 6.7, P = .003) and peroneal (2.5 ± 2.0 vs 4.7 ± 2.0, P = .003) nerve amplitudes were significantly lower in participants with ED compared with those without ED. CONCLUSION: ED affects almost 2/3 of men with T2D and is associated with small nerve fibre damage but preserved nerve conduction and cardiac autonomic function. Corneal confocal microscopy may serve as a useful non-invasive imaging method to identify small fibre damage in patients with T2D and ED.

Non-HDL cholesterol should not generally replace LDL cholesterol in the management of hyperlipidaemia.

PURPOSE OF REVIEW: Non-HDL cholesterol was originally conceived as a therapeutic target for statin treatment in hypertriglyceridaemia when apolipoprotein B100 assays were not widely available. Recently non-HDL cholesterol has been recommended to replace LDL cholesterol in the clinical management of dyslipidaemia routinely in general medical practice. This is misguided. RECENT FINDINGS: Non-HDL cholesterol is heterogeneous, constituting a mixture of triglyceride-rich VLDL, intermediate density lipoprotein and LDL in which small dense LDL is poorly represented and to which VLDL cholesterol contributes increasingly as triglyceride levels rise. This makes it unsuitable as a goal of lipid-lowering treatment or as an arbiter of who should receive such treatment. Results of trials designed to lower LDL cholesterol are not easily translated to non-HDL cholesterol. Fasting is no longer thought essential for screening the general population for raised LDL cholesterol. ApoB100 measurement also does not require fasting even in rarer more extreme lipoprotein disorders encountered in the Lipid Clinic, provides greater precision and specificity and overcomes the problems posed by LDL and non-HDL cholesterol. It is more easily interpreted both in diagnosis and as a therapeutic goal and it includes SD-LDL. SUMMARY: If we are to discourage use of LDL cholesterol, it should be in favour of apoB100 not non-HDL cholesterol.

SQUAT: a Sequencing Quality Assessment Tool for data quality assessments of genome assemblies.

BACKGROUND: With the rapid increase in genome sequencing projects for non-model organisms, numerous genome assemblies are currently in progress or available as drafts, but not made available as satisfactory, usable genomes. Data quality assessment of genome assemblies is gaining importance not only for people who perform the assembly/re-assembly processes, but also for those who attempt to use assemblies as maps in downstream analyses. Recent studies of the quality control, quality evaluation/ assessment of genome assemblies have focused on either quality control of reads before assemblies or evaluation of the assemblies with respect to their contiguity and correctness. However, correctness assessment depends on a reference and is not applicable for de novo assembly projects. Hence, development of methods providing both post-assembly and pre-assembly quality assessment reports for examining the quality/correctness of de novo assemblies and the input reads is worth studying. RESULTS: We present SQUAT, an efficient tool for both pre-assembly and post-assembly quality assessment of de novo genome assemblies. The pre-assembly module of SQUAT computes quality statistics of reads and presents the analysis in a well-designed interface to visualize the distribution of high- and poor-quality reads in a portable HTML report. The post-assembly module of SQUAT provides read mapping analytics in an HTML format. We categorized reads into several groups including uniquely mapped reads, multiply mapped, unmapped reads; for uniquely mapped reads, we further categorized them into perfectly matched, with substitutions, containing clips, and the others. We carefully defined the poorly mapped (PM) reads into several groups to prevent the underestimation of unmapped reads; indeed, a high PM% would be a sign of a poor assembly that requires researchers' attention for further examination or improvements before using the assembly. Finally, we evaluate SQUAT with six datasets, including the genome assemblies for eel, worm, mushroom, and three bacteria. The results show that SQUAT reports provide useful information with details for assessing the quality of assemblies and reads. AVAILABILITY: The SQUAT software with links to both its docker image and the on-line manual is freely available at https://github.com/luke831215/SQUAT .

New Molecules for Treating Resistant Hypertension: a Clinical Perspective.

PURPOSE OF REVIEW: To review the findings of trials evaluating pharmacological treatment approaches for hypertension in general, and resistant hypertension (RH) in particular, and propose future research and clinical directions. RECENT FINDINGS: RH is defined as blood pressure (BP) that remains above target levels despite adherence to at least three antihypertensive medications, including a diuretic. Thus far, clinical trials of pharmacological approaches in RH have focused on older molecules, with spironolactone being demonstrated as the most efficacious fourth-line agent. However, the use of spironolactone in clinical practice is hampered by its side effect profile and the risk of hyperkalaemia in important RH subgroups, such as patients with moderate-severe chronic kidney disease (CKD). Clinical trials of new molecules targeting both well-established and more recently elucidated pathophysiologic mechanisms of hypertension offer a multitude of potential treatment avenues that warrant further evaluation in the context of RH. These include selective mineralocorticoid receptor antagonists (MRAs), aldosterone synthase inhibitors (ASIs), activators of the counterregulatory renin-angiotensin-system (RAS), vaccines, neprilysin inhibitors alone and in combined formulations, natriuretic peptide receptor agonists A (NPRA-A) agonists, vasoactive intestinal peptide (VIP) agonists, centrally acting aminopeptidase A (APA|) inhibitors, antimicrobial suppression of central sympathetic outflow (minocycline), dopamine ß-hydroxylase (DßH) inhibitors and Na+/H+ Exchanger 3 (NHE3) inhibitors. There is a paucity of data from trials evaluating newer molecules for the treatment of RH. Emergent novel molecules for non-resistant forms of hypertension heighten the prospects of identifying new, effective and well-tolerated pharmacological approaches to RH. There is a glaring need to undertake RH-focused trials evaluating their efficacy and clinical applicability.

New Approaches in the Management of Sudden Cardiac Death in Patients with Heart Failure-Targeting the Sympathetic Nervous System.

Cardiovascular diseases (CVDs) have been considered the most predominant cause of death and one of the most critical public health issues worldwide. In the past two decades, cardiovascular (CV) mortality has declined in high-income countries owing to preventive measures that resulted in the reduced burden of coronary artery disease (CAD) and heart failure (HF). In spite of these promising results, CVDs are responsible for ~17 million deaths per year globally with ~25% of these attributable to sudden cardiac death (SCD). Pre-clinical data demonstrated that renal denervation (RDN) decreases sympathetic activation as evaluated by decreased renal catecholamine concentrations. RDN is successful in reducing ventricular arrhythmias (VAs) triggering and its outcome was not found inferior to metoprolol in rat myocardial infarction model. Registry clinical data also suggest an advantageous effect of RDN to prevent VAs in HF patients and electrical storm. An in-depth investigation of how RDN, a minimally invasive and safe method, reduces the burden of HF is urgently needed. Myocardial systolic dysfunction is correlated to neuro-hormonal overactivity as a compensatory mechanism to keep cardiac output in the face of declining cardiac function. Sympathetic nervous system (SNS) overactivity is supported by a rise in plasma noradrenaline (NA) and adrenaline levels, raised central sympathetic outflow, and increased organ-specific spillover of NA into plasma. Cardiac NA spillover in untreated HF individuals can reach ~50-fold higher levels compared to those of healthy individuals under maximal exercise conditions. Increased sympathetic outflow to the renal vascular bed can contribute to the anomalies of renal function commonly associated with HF and feed into a vicious cycle of elevated BP, the progression of renal disease and worsening HF. Increased sympathetic activity, amongst other factors, contribute to the progress of cardiac arrhythmias, which can lead to SCD due to sustained ventricular tachycardia. Targeted therapies to avoid these detrimental consequences comprise antiarrhythmic drugs, surgical resection, endocardial catheter ablation and use of the implantable electronic cardiac devices. Analogous NA agents have been reported for single photon-emission-computed-tomography (SPECT) scans usage, specially the 123I-metaiodobenzylguanidine (123I-MIBG). Currently, HF prognosis assessment has been improved by this tool. Nevertheless, this radiotracer is costly, which makes the use of this diagnostic method limited. Comparatively, positron-emission-tomography (PET) overshadows SPECT imaging, because of its increased spatial definition and broader reckonable methodologies. Numerous ANS radiotracers have been created for cardiac PET imaging. However, so far, [11C]-meta-hydroxyephedrine (HED) has been the most significant PET radiotracer used in the clinical scenario. Growing data has shown the usefulness of [11C]-HED in important clinical situations, such as predicting lethal arrhythmias, SCD, and all-cause of mortality in reduced ejection fraction HF patients. In this article, we discussed the role and relevance of novel tools targeting the SNS, such as the [11C]-HED PET cardiac imaging and RDN to manage patients under of SCD risk.

Acquired low cholesterol: diagnosis and relevance to safety of low LDL therapeutic targets.

PURPOSE OF REVIEW: Acquired hypocholesterolaemia occurs more commonly than inherited hypocholesterolaemia but has received little attention in the literature. In this review, we discuss the causes and underlying mechanisms of acquired hypocholesterolaemia and its relevance to safety of therapeutically induced decreased LDL cholesterol levels. RECENT FINDINGS: Hypocholesterolaemia is increasingly identified as cholesterol testing becomes more widespread in the assessment of cardiovascular risk. Lower therapeutic targets for LDL cholesterol are also being achieved more regularly with the introduction of more intensive cholesterol-lowering regimens. Acquired hypocholesterolaemia may be the presenting feature of treatable diseases. Understanding its mechanisms may also provide new treatment approaches for neoplastic disease, such as breast cancer, and infections, such as tuberculosis. SUMMARY: When hypocholesterolaemia is discovered, it is important to identify its cause. Further research into the pathogenesis of hypocholesterolaemia may provide new therapies for primary diseases underlying it.

Autonomic Regulation of Glucose Homeostasis: a Specific Role for Sympathetic Nervous System Activation.

PURPOSE OF REVIEW: Cardiometabolic disorders such as obesity, metabolic syndrome and diabetes are increasingly common and associated with adverse cardiovascular outcomes. The mechanisms driving these developments are incompletely understood but likely to include autonomic dysregulation. The latest evidence for such a role is briefly reviewed here. RECENT FINDINGS: Recent findings highlight the relevance of autonomic regulation in glucose metabolism and identify sympathetic activation, in concert with parasympathetic withdrawal, as a major contributor to the development of metabolic disorders and an important mediator of the associated adverse cardiovascular consequences. Methods targeting sympathetic overactivity using pharmacological and device-based approaches are available and appear as logical additional approaches to curb the burden of metabolic disorders and alleviate the associated morbidity from cardiovascular causes. While the available data are encouraging, the role of therapeutic inhibition of sympathetic overdrive in the prevention of the metabolic disorders and the associated adverse outcomes requires adequate testing in properly sized randomised controlled trials.

Evidence for more intensive cholesterol lowering.

PURPOSE OF REVIEW: In randomized clinical trials, reduction in cardiovascular disease (CVD) risk with cholesterol-lowering drugs correlates with the LDL cholesterol decrease. However, because the majority have investigated a fixed statin dose, current guidelines disagree about the use of statin dose titration or non-statin adjunctive cholesterol-lowering drugs. RECENT FINDINGS: We conducted a meta-analysis of all randomized controlled trials with CVD end-points, comparing two intensities of lipid-lowering regimens within the same population, using varying statins doses and/or potency, ezetimibe or PCSK9 inhibitors and compared the observed number of patients needed to be treated for 10 years to prevent one CVD event (NNT) with NNT predicted from trials of predominantly single-dose statin.Some 75439 participants in 10 randomized studies were included. The mean 10-year CVD risk in controls was around 50% and the incremental mean LDL cholesterol decrease 0.95 mmol/l (36.7 mg/dl). Observed NNT closely correlated with those predicted from predominantly single-dose statin trials [18.2 and 17.1; Pearson R=0.844 (P=0.001)]. When pre-treatment LDL cholesterol exceeded 4 mmol/l (155 mg/dl), achieving a target LDL cholesterol of 1.8 mmol/l (70 mg/dl) was the most effective strategy. At lower pre-treatment levels, fixed-dose statin equivalent to atorvastatin 80 mg daily was superior. The target of 40% reduction in non-high density lipoprotein cholesterol was least effective regardless of pre-treatment LDL cholesterol. SUMMARY: We conclude that when initial LDL cholesterol exceeds 4 mmol/l and absolute CVD risk demands it, a target value of 1.8 mmol/l should be achieved, if necessary by adding ezetimibe and/or PCSK9 inhibitors to statin treatment.

Liver Fat Measured by MR Spectroscopy: Estimate of Imprecision and Relationship with Serum Glycerol, Caeruloplasmin and Non-Esterified Fatty Acids.

Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantitative estimation of liver fat. Knowledge of its imprecision, which comprises biological variability and measurement error, is required to design therapeutic trials with measurement of change. The role of adipocyte lipolysis in ectopic fat accumulation remains unclear. We examined the relationship between liver fat content and indices of lipolysis, and determine whether lipolysis reflects insulin resistance or metabolic liver disease. Imprecision of measurement of liver fat was estimated from duplicate measurements by MRS at one month intervals. Patients provided fasting blood samples and we examined the correlation of liver fat with indices of insulin resistance, lipolysis and metabolic liver disease using Kendall Tau statistics. The coefficient of variation of liver fat content was 14.8%. Liver fat was positively related to serum insulin (T = 0.48, p = 0.042), homeostasis model assessment (HOMA)-B% (T = -0.48, p = 0.042), and body mass index (BMI) (T = 0.59, p = 0.012); and inversely related to HOMA-S% (T = -0.48, p = 0.042), serum glycerol (T = -0.59, p = 0.014), and serum caeruloplasmin (T = 0.055, p = 0.047). Our estimate of total variability in liver fat content (14.8%) is nearly twice that of the reported procedural variability (8.5%). We found that liver fat content was significantly inversely related to serum glycerol but not to non-esterified fatty acids (NEFA), suggesting progressive suppression of lipolysis. Reduction of caeruloplasmin with increasing liver fat may be a consequence or a cause of hepatic steatosis.

Subset selection of high-depth next generation sequencing reads for de novo genome assembly using MapReduce framework.

BACKGROUND: Recent progress in next-generation sequencing technology has afforded several improvements such as ultra-high throughput at low cost, very high read quality, and substantially increased sequencing depth. State-of-the-art high-throughput sequencers, such as the Illumina MiSeq system, can generate ~15 Gbp sequencing data per run, with >80% bases above Q30 and a sequencing depth of up to several 1000x for small genomes. Illumina HiSeq 2500 is capable of generating up to 1 Tbp per run, with >80% bases above Q30 and often >100x sequencing depth for large genomes. To speed up otherwise time-consuming genome assembly and/or to obtain a skeleton of the assembly quickly for scaffolding or progressive assembly, methods for noise removal and reduction of redundancy in the original data, with almost equal or better assembly results, are worth studying. RESULTS: We developed two subset selection methods for single-end reads and a method for paired-end reads based on base quality scores and other read analytic tools using the MapReduce framework. We proposed two strategies to select reads: MinimalQ and ProductQ. MinimalQ selects reads with minimal base-quality above a threshold. ProductQ selects reads with probability of no incorrect base above a threshold. In the single-end experiments, we used Escherichia coli and Bacillus cereus datasets of MiSeq, Velvet assembler for genome assembly, and GAGE benchmark tools for result evaluation. In the paired-end experiments, we used the giant grouper (Epinephelus lanceolatus) dataset of HiSeq, ALLPATHS-LG genome assembler, and QUAST quality assessment tool for comparing genome assemblies of the original set and the subset. The results show that subset selection not only can speed up the genome assembly but also can produce substantially longer scaffolds. AVAILABILITY: The software is freely available at https://github.com/moneycat/QReadSelector.