Investigating the association between diabetes and carpal tunnel syndrome: A systematic review and meta-analysis approach.

INTRODUCTION: In recent years, several studies have reported on the relationship between diabetes and carpal tunnel syndrome (CTS). However, due to their contradictory results, a systematic review and meta-analysis were conducted to investigate this subject. METHODS: This study is a systematic review and meta-analysis of studies published in ISI Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase databases. Heterogeneity in the studies included in the meta-analysis was evaluated using statistical tests such as the Chi-square test, I2, and forest plots. Publication bias was assessed using Begg's and Egger's tests. RESULTS: This investigation analyzed data from 42 studies conducted between 1985 and 2022, with a total of 3,377,816 participants. The meta-analysis demonstrated that the odds ratio (OR) of CTS in participants with a history of diabetes compared to those without was 1.90 (95% CI: 1.64-2.21; P-value < 0.001). Given that publication bias was observed in this study (Begg's test P-value = 0.01), the modified OR was calculated with consideration of missed studies, which was 1.68 (95% CI: 1.45-1.94; P-value < 0.001). CONCLUSION: The results of this study suggest that diabetic patients have 90% higher odds of developing CTS compared to non-diabetic individuals, which is statistically significant.

A review of experimental and clinical studies on the therapeutic effects of pomegranate (Punica granatum) on non-alcoholic fatty liver disease: Focus on oxidative stress and inflammation.

Non-alcoholic fatty liver disease (NAFLD) is frequently linked to metabolic disorders and is prevalent in obese and diabetic patients. The pathophysiology of NAFLD involves multiple factors, including insulin resistance (IR), oxidative stress (OS), inflammation, and genetic predisposition. Recently, there has been an emphasis on the use of herbal remedies with many people around the world resorting to phytonutrients or nutraceuticals for treatment of numerous health challenges in various national healthcare settings. Pomegranate (Punica granatum) parts, such as juice, peel, seed and flower, have high polyphenol content and is well known for its antioxidant capabilities. Pomegranate polyphenols, such as hydrolyzable tannins, anthocyanins, and flavonoids, have high antioxidant capabilities that can help lower the OS and inflammation associated with NAFLD. The study aimed to investigate whether pomegranate parts could attenuate OS, inflammation, and other risk factors associated with NAFLD, and ultimately prevent the development of the disease. The findings of this study revealed that: 1. pomegranate juice contains hypoglycemic qualities that can assist manage blood sugar levels, which is vital for avoiding and treating NAFLD. 2. Polyphenols from pomegranate flowers increase paraoxonase 1 (PON1) mRNA and protein levels in the liver, which can help protect liver enzymes and prevent NAFLD. 3. Punicalagin (PU) is one of the major ellagitannins found in pomegranate, and PU-enriched pomegranate extract (PE) has been shown to inhibit HFD-induced hyperlipidemia and hepatic lipid deposition in rats. 4. Pomegranate fruit consumption, which is high in antioxidants, can decrease the activity of AST and ALT (markers of liver damage), lower TNF-α (a marker of inflammation), and improve overall antioxidant capacity in NAFLD patients. Overall, the polyphenols in pomegranate extracts have antioxidant, anti-inflammatory, hypoglycemic, and protective effects on liver enzymes, which can help prevent and manage NAFLD effects on liver enzymes, which can help prevent and manage NAFLD.

Unraveling mechanistic insights into the role of microbiome in neurogenic hypertension: A comprehensive review.

Neurogenic hypertension, a complex and multifactorial cardiovascular disorder, is known to be influenced by various genetic, environmental, and lifestyle factors. In recent years, there has been growing interest in the role of the gut microbiome in hypertension pathogenesis. The bidirectional communication between the gut microbiota and the central nervous system, known as the microbiota-gut-brain axis, has emerged as a crucial mechanism through which the gut microbiota exerts its influence on neuroinflammation, immune responses, and blood pressure regulation. Recent studies have shown how the microbiome has a substantial impact on a variety of physiological functions, such as cardiovascular health. The increased sympathetic activity to the gut may cause microbial dysbiosis, increased permeability of the gut, and increased inflammatory reactions by altering a number of intestinal bacteria producing short-chain fatty acids (SCFAs) and the concentrations of lipopolysaccharide (LPS) in the plasma. Collectively, these microbial metabolic and structural compounds stimulate sympathetic stimulation, which may be an important stage in the onset of hypertension. The result is an upsurge in peripheral and central inflammatory response. In addition, it has recently been shown that a link between the immune system and the gut microbiota might play a significant role in hypertension. The therapeutic implications of the gut microbiome including probiotic usage, prebiotics, dietary modifications, and fecal microbiota transplantation in neurogenic hypertension have also been found. A large body of research suggests that probiotic supplementation might help reduce chronic inflammation and hypertension that have an association with dysbiosis in the gut microbiota. Overall, this review sheds light on the intricate interplay between the gut microbiome and neurogenic hypertension, providing valuable insights for both researchers and clinicians. As our knowledge of the microbiome's role in hypertension expands, novel therapeutic strategies and diagnostic biomarkers may pave the way for more effective management and prevention of this prevalent cardiovascular disorder. Exploring the potential of the microbiome in hypertension offers an exciting avenue for future research and offers opportunities for precision medicine and improved patient care.

Results and lessons learned from the sbv IMPROVER metagenomics diagnostics for inflammatory bowel disease challenge.

A growing body of evidence links gut microbiota changes with inflammatory bowel disease (IBD), raising the potential benefit of exploiting metagenomics data for non-invasive IBD diagnostics. The sbv IMPROVER metagenomics diagnosis for inflammatory bowel disease challenge investigated computational metagenomics methods for discriminating IBD and nonIBD subjects. Participants in this challenge were given independent training and test metagenomics data from IBD and nonIBD subjects, which could be wither either raw read data (sub-challenge 1, SC1) or processed Taxonomy- and Function-based profiles (sub-challenge 2, SC2). A total of 81 anonymized submissions were received between September 2019 and March 2020. Most participants' predictions performed better than random predictions in classifying IBD versus nonIBD, Ulcerative Colitis (UC) versus nonIBD, and Crohn's Disease (CD) versus nonIBD. However, discrimination between UC and CD remains challenging, with the classification quality similar to the set of random predictions. We analyzed the class prediction accuracy, the metagenomics features by the teams, and computational methods used. These results will be openly shared with the scientific community to help advance IBD research and illustrate the application of a range of computational methodologies for effective metagenomic classification.

Preparation of Nano/Microcapsules of Ozonated Olive Oil in Hyaluronan Matrix and Analysis of Physicochemical and Microbiological (Biological) Properties of the Obtained Biocomposite.

Hydrogels, based on natural polymers, such as hyaluronic acid, are gaining an increasing popularity because of their biological activity. The antibacterial effect of ozone is widely known and used, but the instability the gas causes, severely limits its application. Ozone entrapment in olive oil by its reaction with an unsaturated bond, allows for the formation of stable, therapeutically active ozone derivatives. In this study, we obtained an innovative hydrogel, based on hyaluronic acid containing micro/nanocapsules of ozonated olive oil. By combination of the biocompatible polymer with a high regenerative capacity and biologically active ingredients, we obtained a hydrogel with regenerative properties and a very weak inhibitory effect against both bacterial commensal skin microbiota and pathogenic Candida-like yeasts. We assessed the stability and rheological properties of the gel, determined the morphology of the composite, using scanning electron microscopy (SEM) and particle size by the dynamic light scattering (DLS) method. We also performed Attenuated total reflectance Fourier transform infrared (FTIR-ATR) spectroscopy. The functional properties, including the antimicrobial potential were assessed by the microbiological analysis and in vitro testing on the HaCat human keratinocyte cell line. The studies proved that the obtained emulsions were rheologically stable, exhibited an antimicrobial effect and did not show cytotoxicity in the HaCat keratinocyte model.

Crowdsourced benchmarking of taxonomic metagenome profilers: lessons learned from the sbv IMPROVER Microbiomics challenge.

BACKGROUND: Selection of optimal computational strategies for analyzing metagenomics data is a decisive step in determining the microbial composition of a sample, and this procedure is complex because of the numerous tools currently available. The aim of this research was to summarize the results of crowdsourced sbv IMPROVER Microbiomics Challenge designed to evaluate the performance of off-the-shelf metagenomics software as well as to investigate the robustness of these results by the extended post-challenge analysis. In total 21 off-the-shelf taxonomic metagenome profiling pipelines were benchmarked for their capacity to identify the microbiome composition at various taxon levels across 104 shotgun metagenomics datasets of bacterial genomes (representative of various microbiome samples) from public databases. Performance was determined by comparing predicted taxonomy profiles with the gold standard. RESULTS: Most taxonomic profilers performed homogeneously well at the phylum level but generated intermediate and heterogeneous scores at the genus and species levels, respectively. kmer-based pipelines using Kraken with and without Bracken or using CLARK-S performed best overall, but they exhibited lower precision than the two marker-gene-based methods MetaPhlAn and mOTU. Filtering out the 1% least abundance species-which were not reliably predicted-helped increase the performance of most profilers by increasing precision but at the cost of recall. However, the use of adaptive filtering thresholds determined from the sample's Shannon index increased the performance of most kmer-based profilers while mitigating the tradeoff between precision and recall. CONCLUSIONS: kmer-based metagenomic pipelines using Kraken/Bracken or CLARK-S performed most robustly across a large variety of microbiome datasets. Removing non-reliably predicted low-abundance species by using diversity-dependent adaptive filtering thresholds further enhanced the performance of these tools. This work demonstrates the applicability of computational pipelines for accurately determining taxonomic profiles in clinical and environmental contexts and exemplifies the power of crowdsourcing for unbiased evaluation.

Formation and Investigation of Physicochemical, Biological and Bacteriostatic Properties of Nanocomposite Foils Containing Silver Nanoparticles and Graphene Oxide in Hyaluronic Acid Matrix.

Natural polysaccharides, including hyaluronic acid, find a wide range of applications in biomedical sciences. There is a growing interest in nanocomposites containing hyaluronic acid and nanoparticles such as nanometals or graphene. In this study, we prepared foils of pure sodium hyaluronate and sodium hyaluronate containing nanosilver, graphene oxide, nanosilver/graphene oxide and characterized their properties. UV-vis spectroscopy and scanning electron microscopy (SEM) confirmed the formation of 10-20 nm silver nanoparticles. The structural changes were investigated using Fourier transforms infrared (FTIR) spectra and size exclusion chromatography. The obtained results suggest changes in molecular weights in the samples containing nanoparticles, which was highest in a sample containing nanosilver/graphene oxide. We also assessed the mechanical properties of the foils (thickness, tensile strength and elongation at break) and their wettability. The foils containing nanosilver and nanosilver/graphene oxide presented bacteriostatic activity against E. coli, Staphylococcus spp. and Bacillus spp., which was not observed in the control and sample containing graphene oxide. The composites containing graphene oxide and nanosilver/graphene oxide exhibited a cytotoxic effect on human melanoma WM266-4 cell lines (ATCC, Manassas, VA, USA).

Relationships between circulating galectin-3, extracellular matrix fibrosis and outcomes in dilated cardiomyopathy.

BACKGROUND: Galectin-3 is an emerging biomarker in cardiovascular disease. Myocardial galectin-3 is involved in the pathology of cardiac fibrosis; however, the role of circulating galectin-3 is not yet established. OBJECTIVES: To assess the relationships between circulating galectin-3, fibrosis and outcomes in dilated cardiomyopathy (DCM). MATERIAL AND METHODS: We included 70 patients (age: 48 ±12.1 years, ejection fraction (EF) 24.4 ±7.4%) with new-onset DCM (n = 35, ≤6 months). Galectin-3 and procollagen type I and III (PICP, PINP, PIIICP, and PIIINP), transforming growth factor ß (TGF-ß), connective tissue growth factor (CTGF), osteopontin (OPN), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitor (TIMP-1) were determined in serum at baseline and after 3 and 12 months. Patients underwent endomyocardial biopsy. The endpoint was a combination of death and urgent hospitalization at 12 months. RESULTS: Galectin-3 did not correlate with biopsy-determined fibrosis. Baseline galectin-3 correlated with OPN,, TIMP-1, PIIICP, and MMP-2. In new-onset DCM, galectin-3 levels at baseline were higher than at 3 and 12 months, whereas in chronic DCM there was no difference. Galectin-3 was a predictor of the endpoint (hazard ratio (HR) = 1.115; 95% confidence interval (95% CI) = 1.009-1.231; p < 0.05). The best cut-off value was 14.54 ng/mL (area under the curve (AUC) = 0.67). Patients with galectin-3 ≥14.54 ng/mL had an increased risk of events (HR = 2.569; 95% CI = 1.098-6.009; p < 0.05). CONCLUSIONS: Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.

Inflammatory Bowel Disease-Associated Changes in the Gut: Focus on Kazan Patients.

BACKGROUND: Several studies have highlighted the role of host-microbiome interactions in the pathogenesis of inflammatory bowel disease (IBD), resulting in an increasing amount of data mainly focusing on Western patients. Because of the increasing prevalence of IBD in newly industrialized countries such as those in Asia, the Middle East, and South America, there is mounting interest in elucidating the gut microbiota of these populations. We present a comprehensive analysis of several IBD-related biomarkers and gut microbiota profiles and functions of a unique population of patients with IBD and healthy patients from Kazan (Republic of Tatarstan, Russia). METHODS: Blood and fecal IBD biomarkers, serum cytokines, and fecal short-chain fatty acid (SCFA) content were profiled. Finally, fecal microbiota composition was analyzed by 16S and whole-genome shotgun sequencing. RESULTS: Fecal microbiota whole-genome sequencing confirmed the presence of classic IBD dysbiotic features at the phylum level, with increased abundance of Proteobacteria, Actinobacteria, and Fusobacteria and decreased abundance of Firmicutes, Bacteroidetes, and Verrucomicrobia. At the genus level, the abundance of both fermentative (SCFA-producing and hydrogen (H2)-releasing) and hydrogenotrophic (H2-consuming) microbes was affected in patients with IBD. This imbalance was confirmed by the decreased abundance of SCFA species in the feces of patients with IBD and the change in anaerobic index, which mirrors the redox status of the intestine. CONCLUSIONS: Our analyses highlighted how IBD-related dysbiotic microbiota-which are generally mainly linked to SCFA imbalance-may affect other important metabolic pathways, such as H2 metabolism, that are critical for host physiology and disease development.

Relations between circulating and myocardial fibrosis-linked microRNAs with left ventricular reverse remodeling in dilated cardiomyopathy.

BACKGROUND: Left ventricular reverse remodeling (LVRR) determines clinical status and outcomes in dilated cardiomyopathy (DCM). The extent of myocardial fibrosis is connected to the systolic function of the heart. The recent discovery of the contribution of microRNAs (miRs) to the regulation of cardiac remodeling, LVRR and fibrosis warrants exploration. OBJECTIVES: The aim of the study was to examine the predictive value of circulating and myocardial miR expression for LVRR in DCM. MATERIAL AND METHODS: Seventy consecutive DCM patients (age 48 ±12.1 years, 90% male, ejection fraction (EF) 24.4% ±7.4%) were included in the study. At baseline, all patients underwent clinical assessment, echocardiography, venous blood sampling, and right ventricular endomyocardial biopsy. Circulating and myocardial miRs (miR-21, -26, -29, -30, -133a, and -423) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). LVRR was defined as an increase in EF ≥ 10%, accompanied by a decrease in left ventricle end-diastolic diameter (LVEDd) ≥10% or LVEDd ≤ 33 mm/m2 between baseline and 3-month follow-up. RESULTS: At the 3-month follow-up, 4 patients had died and 3 patients had incomplete data. The remaining patients were divided according to the presence of LVRR into LVRR-present (n = 32, 51%) and LVRR-absent (n = 31, 49%) groups. Out of all the circulating and tissue miRs under study, only myocardial expression of miR-133a significantly differed between the LVRR-present and LVRR-absent group (1.22 (0.47-1.90) vs 0.61 (0.25-0.99) ΔCq, respectively, p < 0.01). miR-133a was found to be a significant LVRR predictor in unadjusted (odds ratio (OR) = 2.81 (1.23-6.40), p < 0.05) and adjusted for duration of disease, left ventricle end-diastolic (LVED) volume (LVEDvol), hs-troponin-T, and NT-proBNP (OR = 5.20 (1.13-24.050, p < 0.05) models. CONCLUSIONS: From all of the circulating and tissue miRs, only myocardial miR-133a showed increased expression in LVRR-present patients and was found an independent LVRR predictor. This indicates a link between miR-133 and cardiac remodeling in DCM.

Functional properties of composites containing silver nanoparticles embedded in hyaluronan and hyaluronan-lecithin matrix.

The rapid progress of nanotechnology triggers the development of nanomedicine. As the antimicrobial properties of nanosilver are well known, there is a huge interest in the synthesis of silver nanoparticles using environmentally-friendly methods. In this study we described the functional (rheological, mechanical, surface, structural) properties of gels and foils containing silver nanoparticles embedded in hyaluronan and hyaluronan-lecithin matrix prepared using the methods of green chemistry. The study showed that the addition of silver strengthened the structure of Hyal foil, but reduced the stretch of the sample and that lecithin weakened the mechanical properties of the composites. Also, the presence of nanosilver made the studied foils partially hydrophilic, while these with lecithin were more hydrophobic. The results of the study are significant for the adaptation of the investigated materials to their potential applications.

Taxonomic classification and abundance estimation using 16S and WGS-A comparison using controlled reference samples.

The assessment of microbiome biodiversity is the most common application of metagenomics. While 16S sequencing remains standard procedure for taxonomic profiling of metagenomic data, a growing number of studies have clearly demonstrated biases associated with this method. By using Whole Genome Shotgun sequencing (WGS) metagenomics, most of the known restrictions associated with 16S data are alleviated. However, due to the computationally intensive data analyses and higher sequencing costs, WGS based metagenomics remains a less popular option. Selecting the experiment type that provides a comprehensive, yet manageable amount of information is a challenge encountered in many metagenomics studies. In this work, we created a series of artificial bacterial mixes, each with a different distribution of skin-associated microbial species. These mixes were used to estimate the resolution of two different metagenomic experiments - 16S and WGS - and to evaluate several different bioinformatics approaches for taxonomic read classification. In all test cases, WGS approaches provide much more accurate results, in terms of taxa prediction and abundance estimation, in comparison to those of 16S. Furthermore, we demonstrate that a 16S dataset, analysed using different state of the art techniques and reference databases, can produce widely different results. In light of the fact that most forensic metagenomic analysis are still performed using 16S data, our results are especially important.

Kinetics of selected serum markers of fibrosis in patients with dilated cardiomyopathy and different grades of diastolic dysfunction of the left ventricle.

BACKGROUND: Fibrosis of the extracellular matrix (ECM) in dilated cardiomyopathy (DCM) is common and compromises both systolic and diastolic function. The aim of this study was to investigate the kinetics of ECM fibrosis markers over a 12 month follow-up in patients with DCM based on the severity of diastolic dysfunction (DD). METHODS: Seventy consecutive DCM patients (48 ± 12.1 years, ejection fraction 24.4 ± 7.4%) were included in the study. The grade of DD was determined using the ASE/EACVI algorithm. Markers of ECM fibrosis were measured at baseline and at 3 and 12 month follow-ups: collagen type I and III (PICP, PINP, PIIICP, PIIINP), transforming growth factor beta-1 (TGF1-b), connective tissue growth factor (CTGF) and galectin-3 were measured. RESULTS: Patients were divided into three groups according to DD severity: 30 patients with grade I, 18 with grade II and 22 with grade III of DD. Levels of PICP, PINP were increased over a 12-month period, while PIIINP decreased and PIIICP unchanged. Levels of TGF1-b decreased from the 3 to the 12-month points in grade I and II DD, and in grade III they remained unchanged. Levels of CTGF decreased over 12 months in grade III DD but were unchanged in grades I and II. Galectin-3 levels remained the same over all observation periods, irrespective of DD grade. CONCLUSIONS: Regardless of the DD grade, markers of collagen type I synthesis increased, markers of collagen type III decreased. Levels of TGF and CTGF had a tendency to decrease. Galectin-3 was revealed not to be a marker discriminating the severity of DD.

BacTag - a pipeline for fast and accurate gene and allele typing in bacterial sequencing data based on database preprocessing.

BACKGROUND: Bacteria carry a wide array of genes, some of which have multiple alleles. These different alleles are often responsible for distinct types of virulence and can determine the classification at the subspecies levels (e.g., housekeeping genes for Multi Locus Sequence Typing, MLST). Therefore, it is important to rapidly detect not only the gene of interest, but also the relevant allele. Current sequencing-based methods are limited to mapping reads to each of the known allele reference, which is a time-consuming procedure. RESULTS: To address this limitation, we developed BacTag - a pipeline that rapidly and accurately detects which genes are present in a sequencing dataset and reports the allele of each of the identified genes. We exploit the fact that different alleles of the same gene have a high similarity. Instead of mapping the reads to each of the allele reference sequences, we preprocess the database prior to the analysis, which makes the subsequent gene and allele identification efficient. During the preprocessing, we determine a representative reference sequence for each gene and store the differences between all alleles and this chosen reference. Throughout the analysis we estimate whether the gene is present in the sequencing data by mapping the reads to this reference sequence; if the gene is found, we compare the variants to those in the preprocessed database. This allows to detect which specific allele is present in the sequencing data. Our pipeline was successfully tested on artificial WGS E. coli, S. pseudintermedius, P. gingivalis, M. bovis, Borrelia spp. and Streptomyces spp. data and real WGS E. coli and K. pneumoniae data in order to report alleles of MLST house-keeping genes. CONCLUSIONS: We developed a new pipeline for fast and accurate gene and allele recognition based on database preprocessing and parallel computing and performed better or comparable to the current popular tools. We believe that our approach can be useful for a wide range of projects, including bacterial subspecies classification, clinical diagnostics of bacterial infections, and epidemiological studies.

Relationships between left ventricular geometry and remodeling in dilated cardiomyopathy.

BACKGROUND: Since left ventricular reverse remodeling (LVRR) and sphericity index (SI) are correlated with DCM patients' survival, we attempted to establish the relationship between LVRR, SI and left ventricle (LV) dimensions. METHODS: In 70 DCM patients, we measured EF, LV transverse (sLVd) and longitudinal (lLVd) diameters at hospital admission, then after 3 and 12 months. SI was assessed thus: SI=sLVd/lLVd. RESULTS: LVRR was present in 32 patients (52%). SI measurements were similar in LVRR-present and -absent groups at baseline (0.71 vs. 0.70) and differed after 3 and 12 months (0.61 vs. 0.72, P<0.005; 0.59 vs. 0.73, P<0.001; respectively). During 12 months, SI and sLVd decreased in the LVRR-present (0.71 vs. 0.61 vs. 0.59, P<0.05; 5.75 vs. 5.00 vs. 4.82 cm, P<0.001; respectively) and increased in the LVRR-absent cohort (0.70 vs. 0.72 vs. 0.73, P<0.001; 6.01 vs. 6.15 vs. 6.67, P<0.001; respectively). lLVd remained stable (8.23 vs. 8.16 vs. 8.38cm; 8.66 vs. 8.85 vs. 9.13 cm; respectively). SI was significantly correlated with sLVd but not with lLVd. At 3-month follow-up, SI (P<0.005, OR=14000 [95% CI: 5 - 3.9*107]) was found to be a significant LVRR predictor via univariate logistic regression. CONCLUSIONS: To summarize, changes in sLVd are crucial for changes in LV geometry, whereas lLVd has a negligible effect on this process. The presence of LVRR was not always associated with an improvement in SI and its absence with increase in SI. Since the assessment of SI is less complex than LVRR, SI as a significant LVRR predictor can be useful part of a regular echocardiography examination.

Comparison of two European models estimating risk of -sudden cardiac death in hypertrophic cardiomyopathy.

Objective Hypertrophic cardiomyopathy (HCM) is associated with a risk of sudden cardiac death (SCD). Several models have been developed to estimate SCD risk and guide preventive therapy. The comparison of the previous 2003 with novel 2014 SCD risk models have never been studied. Methods Over a year we included 103 consecutive HCM patients without previous cardiac arrest and/or ICD implanted (65% males; aged 53.3 ± 13.9 years; mean EF 62.3 ± 18%). The SCD risk was calculated for each patient. Results Based on the 2003 model, patients had following scores: 0 points -15 (15%) patients, 1-28 (27%), 2-34 (33%), 3-18 (17%), ≥ 4-8 (8%). According to the 2014 model 83 (80%) had low risk, 12 (12%) intermediate risk, and only 8 (8%) high risk. Patients who had an intermediate or high risk in the 2003 model but a low risk in 2014 model were the oldest, experienced less frequently syncope and nsVT, but had more often abnormal blood pressure response to exercise and an intermediate LVOT gradient in comparison to the patients who had consistently low or high risk in both models. Conclusions Calculation of SCD risk using two models provides completely different risk estimates and consequently different guidance on SCD primary prevention. According to the 2003 model up to 85% of patients have indications for ICD, whereas based on the 2014 risk model only 20% of the patients had non-negligible SCD risk and are candidates for ICD therapy. SCD risk markers, used in the 2003 and 2014 models, have various discriminating power.

Left ventricular reverse remodeling is not related to biopsy-detected extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy, regardless of the definition used for LVRR.

Left ventricular reverse remodeling (LVRR) is reported in dilated cardiomyopathy (DCM) patients (pts). However, numerous definitions of LVRR exist. Measurements of serum markers of fibrosis provide insight into myocardial fibrosis. The relationship between LVRR and fibrosis is poorly understood. From July 2014 until October 2015, we included 63 consecutive DCM pts (48 ± 12.1 years, EF 24.4 ± 7.4%) with completed baseline and 3-month follow-up echocardiograms. LVRR was assessed on the basis of four differing definitions. Procollagens type I and III carboxy- and amino-terminal peptides (PICP, PINP, PIIICP, and PIIINP), collagen 1, ostepontin, tumor growth factor beta-1, connective tissue growth factor, and matrix metalloproteinases (MMP-2, MMP-9), and their tissue inhibitor (TIMP-1) were measured in serum. In addition, all pts underwent right ventricular endomyocardial biopsy. Depending on the definition chosen, LVRR could be diagnosed in between 14.3 and 50.8% pts. Regardless of the LVRR definition used, the frequency of LVRR was similar in fibrosis negative and positive DCM. Minor differences of markers of fibrosis were detected between pts with and without LVRR. For every LVRR definition, adjusted and unadjusted models were constructed to evaluate the predictive value of serum fibrosis parameters. Only an increase of TIMP-1 by 1 ng/ml was found to independently increase the probability of LVRR by 0.016%. The choice of a particular definition of LVRR determines the final diagnosis, and this has a profound impact on subsequent management. LVRR is unrelated to biopsy-detected ECM fibrosis. Serum markers of fibrosis are only weakly related to LVRR, and are not of use in the prediction of LVRR.

Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy.

BACKGROUND: Fibrosis of extracellular matrix (ECM) in dilated cardiomyopathy (DCM) corresponds to the myocardial over-production of various types of collagens. However, mechanism of this process is poorly understood. OBJECTIVE: To investigate whether enhanced metabolism of ECM occur in DCM. METHODS: Seventy consecutive DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4 %) and 20 healthy volunteers were studied. Based on symptoms duration, pts were divided into new-onset (n = 35, 6 months) and chronic DCM (n = 35, >6 months). Markers of collagen type I and III synthesis-procollagen type I carboxy- and amino-terminal peptides (PICP and PINP) and procollagen type III carboxy- and amino-terminal peptides (PIIICP and PIIINP), collagen 1 (col-1), ECM metabolism controlling factors-tumor growth factor beta-1 (TGF1-ß), connective tissue growth factor (CTGF), and ECM degradation enzymes-matrix metalloproteinases (MMP-2, MMP-9) and their tissue inhibitor (TIMP-1) were measured in serum. All pts underwent right ventricular endomyocardial biopsy to study ECM fibrosis. RESULTS: The presence of fibrosis was detected in 24 (34.3 %) pts and was more prevalent in chronic DCM [17 (48.6 %) vs. 7 (20 %), p < 0.01]. The levels of PIIINP [4.41 (2.17-6.08) vs. 3.32 (1.69-5.02) ng/ml, p < 0.001], CTGF [3.82 (0.48-23.87) vs. 2.37 (0.51-25.32) ng/ml, p < 0.01], MMP-2 [6.06 (2.72-14.8) vs. 4.43 (2.27-7.4) ng/ml, p < 0.001], MMP-9 [1.98 (0.28-9.25) vs. 1.01 (0.29-3.59) ng/ml, p < 0.002)], and TIMP-1 [15.29 (1.8-36.17) vs. 2.61 (1.65-24.09) ng/ml, p < 0.004] were significantly higher in DCM, whereas levels of col-1 [57.7 (23.1-233.4) vs. 159.4 (31.2-512.9) pg/ml, p < 0.001] were significantly lower in DCM compared to controls. There were no differences in all measured serum markers of ECM metabolism between newonset and chronic DCM and as well as fibrosis positive and negative pts. Fibrosis was weakly correlated only with the duration of DCM (r = 0.23, p < 0.05), however, not a single serum marker of fibrosis correlated with fibrosis. Neither unadjusted nor adjusted models, constructed from serum markers of ECM metabolism, predicted the probability of myocardial fibrosis. CONCLUSIONS: Dynamics of ECM turnover in DCM is high, which is reflected by the increased levels CTGF and degradation enzymes. Synthesis of collagen type III prevailed over collagen type I. ECM metabolism was not different in DCM regardless of the duration of the disease and status of myocardial fibrosis. Serum markers of ECM metabolism were found not to be useful for the prediction of myocardial fibrosis in DCM.

Determining the quality and complexity of next-generation sequencing data without a reference genome.

We describe an open-source kPAL package that facilitates an alignment-free assessment of the quality and comparability of sequencing datasets by analyzing k-mer frequencies. We show that kPAL can detect technical artefacts such as high duplication rates, library chimeras, contamination and differences in library preparation protocols. kPAL also successfully captures the complexity and diversity of microbiomes and provides a powerful means to study changes in microbial communities. Together, these features make kPAL an attractive and broadly applicable tool to determine the quality and comparability of sequence libraries even in the absence of a reference sequence. kPAL is freely available at https://github.com/LUMC/kPAL webcite.