Potential application of hydroxypropyl methylcellulose/shellac embedded with graphene oxide/TiO2-Nps as natural packaging film.

Graphene oxide (GO), TiO2-NPs, HPMC, and shellac are environmentally green polymers and nanocomposites. This work aimed to create biodegradable composite films made of HPMC/shellac, HPMC/shellac-GO, and HPMC/shellac-GO/TiO2-NPs by film casting. TiO2-HPMC/shellac-GO matrix's dispersibility and mixing ability were characterized and observed using FTIR and XRD. XRD analysis shows that the crystallinity decreased within the composites due to breaking H-bonding. Compared to HPMC/shellac, TGA/DTG demonstrated the composite films' superior thermal stability. TiO2 (0.08-0.16 %) was cast into a composite film comprising HPMC, shellac, and GO. The homogeneity of TiO2 distribution in the composite film was shown using a SEM, which was also used to display the morphology of nanocomposite films. Nanocomposite films' thickness, air permeability, tensile strength, Young's modulus, and burst strength were examined. The results demonstrated that natural films prepared by a combination of shellac/GO with HPMC enhanced the fabricating of films' properties, the tensile strength increased by 231 % (from 16 to 53 MPa) in HPMC and HPSG2 (HPMC 1.9 g/shellac 0.25 g/GO 0.125 g in 100 mL) respectively, whereas the contact angle did not change. And after addition of TiO2-NPs, there were high enhancements in HPMC films' properties, such tensile strength increased by 212 % (from 16 to 50 MPa), burst strength increased by 20.96 % (3.1 to 3.75 Kg/cm2), and the contact angle by 60.86 % (48 to 74°) in HPMC and HPSGT2 respectively. Compared to HPMC films, films exhibited the highest levels of antibacterial activity against E. coli, B. mycoides, and C. albicans. So, the composite films from HPMC/shellac/GO/TiO2-NPs are promising potential packaging materials.

Living Longer or Better-Patient's Choice in Cardiac Surgery Is Gender-Dependent-A Multicenter Study.

In view of the increasing age of cardiac surgery patients, questions arise about the expected postoperative quality of life and the hoped-for prolonged life expectancy. Little is known so far about how these, respectively, are weighted by the patients concerned. This study aims to obtain information on the patients' preferences. Between 2015 and 2017, data were analyzed from 1349 consecutive patients undergoing cardiac surgery at seven heart centers in Germany. Baseline data regarding the patient's situation as well as a questionnaire regarding quality of life versus lifespan were taken preoperatively. Patients were divided by age into four groups: below 60, 60-70, 70-80, and above 80 years. As a result, when asked to decide between quality of life and length of life, about 60% of the male patients opted for quality of life, independent of their age. On the other hand, female patients' preference for quality of life increased significantly with age, from 51% in the group below sixty to 76% in the group above eighty years. This finding suggests that female patients adapt their preferences with age, whereas male patients do not. This should impact further the treatment decisions of elderly patients in cardiac surgery within a shared decision-making process.

Elucidation of the genetic causes of bicuspid aortic valve disease.

AIMS: The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. METHODS AND RESULTS: We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10-08) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10-16), GATA4 (P = 1.61 × 10-09), and TEX41 (P = 7.68 × 10-04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. CONCLUSION: Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

Regional Vascular Changes and Aortic Dilatation in Pediatric Patients With Bicuspid Aortic Valve.

BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital heart disease, often associated with valve dysfunction, coarctation of the aorta, and ascending aorta dilatation. Aortic dilatation might result from abnormal regional hemodynamics or inherent vascular disease. Vascular function in pediatric BAV remains poorly characterized. METHODS: A cross-sectional study was performed to evaluate vascular function in 142 children with BAV aged 7-18 years compared with healthy control children. Echocardiography was performed to assess aortic dimensions, BAV function, and vascular function (aortic arch pulse wave velocity [PWV]), carotid intima media thickness, and aortic stiffness and distensibility). Carotid-femoral and carotid-radial PWV were assessed using tonometry. Vascular function was compared for 4 patient groups stratified according to aortic dilatation and a history of coarctation of the aorta. Multivariate regression analysis was performed to determine predictors of aortic dilatation. RESULTS: Children with BAV had stiffer and less distensible ascending aortas with higher aortic arch PWV compared with control children. Carotid-femoral and carotid-radial PWV were not increased in patients with BAV, and the vascular assessment of the abdominal aorta was unremarkable. Multivariate regression revealed that aortic arch PWV was the only vascular function parameter that was associated with aortic dilatation. CONCLUSIONS: Children with BAV have differences in vascular function that are confined to their proximal aorta, even in normal functioning BAV. The observed differences in vascular function are likely multifactorial, with contributions from abnormal regional flow and a potential localized primary aortopathy.

Valve disease and aortopathy associations of bicuspid aortic valve phenotypes differ between men and women.

OBJECTIVE: Determine whether associations between bicuspid aortic valve (BAV) phenotypes, valve disease and aortopathy differ between sexes. METHODS: 1045 patients with BAV (76.0% men, n=794) from two surgical centres were included in this cross-sectional study. Valve phenotype was classified intraoperatively as right-left (RL), right-non-coronary (RN), left-non-coronary (LN) or 2-sinus BAV. Echocardiography was used to determine type and degree of valve disease, and aortic dimensions. Aortic dilatation was defined as diameter ≥4.5 cm. RESULTS: RL was the most common phenotype (73.6%), followed by RN (16.2%), 2-sinus BAV (9.2%) and LN (1.1%), with no difference in phenotype distribution between men and women (p=0.634). Aortic valve insufficiency (AI) prevalence differed significantly with valve phenotype in men (p=0.047), with RL and LN having the highest prevalence (34.1% and 44.0%, respectively). In women, RN had a higher proportion of AI than RL (21.3% vs 7.3%, p=0.017). Men with RL had larger root dimensions, in particular at the sinus (mean difference 0.24 cm compared with RN, p=0.002). Men with 2-sinus BAV had the highest prevalence of root phenotype dilatation (7.0%, other phenotypes ≤2.3%, p=0.031), whereas women with 2-sinus BAV did not have root dilatation and smaller sinus dimensions (mean difference: 0.35 cm compared with RL, p=0.021). Aortic root segments were larger in men with AI compared with aortic stenosis (sinus mean difference: 0.40 cm, p<0.001). The difference was even larger in women (mean difference: 0.78 cm, p<0.001), and women with AI also had larger tubular segments (mean difference: 0.61 cm, p=0.001). CONCLUSIONS: There are significant sex differences in clinical associations of BAV phenotypes, which should be considered in further studies on the role of phenotypes in individualised patient management.

Evaluation of the Aortopathy in the Ascending Aorta: The Novelty of Using Matrix-Assisted Laser Desorption/Ionization Imaging.

PURPOSE: Histopathological evaluation presents conflicting reports regarding aortic abnormalities. The authors aim to present proof-of-concept study to explore the feasibility of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) in combination with histopathology for characterizing alterations in the aneurysmal ascending formalin-fixed paraffin-embedded (FFPE) aorta tissue. EXPERIMENTAL DESIGN: The authors assess FFPE specimens from patients with a dilated aorta and bicuspid aortic valve (BAV), those with a standard tricuspid aortic valve (TAV), and those with Marfan syndrome (MFS) via histopathology and grade the conditions for elastic fiber fragmentation (EFF) and MALDI-IMS. The proteins using liquid chromatographic-mass spectrometry are identified and the results are confirmed by immunohistochemistry. RESULTS: There is significant difference in terms of EFF between MFS and BAV, and TAV and BAV. Characteristic peptide signatures and m/z values in the EFF facilitate the characterization among the aortic specimens of BAV, MFS, and TAV. The m/z values from the aortic alpha smooth muscle actin and myosin heavy chains significantly increase in BAV compared with MFS and TAV. These findings are confirmed by immunohistochemistry. CONCLUSION: The results represent a strategy that uses MALDI-IMS in combination with histopathology as promising approaches to characterize spatial alteration in the structure of the aneurysmal ascending aorta.

Polysaccharides, Protein and Lipid -Based Natural Edible Films in Food Packaging: A Review.

Polysaccharides, such as pectin, starch, alginate, carrageenan, and xanthan gum, have been used as biopolymer materials to create coatings and edible films to reduce traditional plastic packages. Petrochemical polymers, extensively used for food packaging, are non-renewable and non-biodegradable and need landfills. Thus, there is a requirement to find alternative packaging materials that are easily degradable and renewable. Natural edible polymers are the materials made from natural edible constituents that can be consumed by animals or human beings with no health risk. Since they are directly consumed with food, nothing is left for disposal. Polysaccharides, Protein and Lipid-Based Natural edible polymers are used to make coatings and edible films surrounding the surface of the food. These natural edible polymers are generally categorized into polysaccharides, lipids and proteins. This review article summarizes the importance of various natural polymers used for making coatings and edible films.

Predictors of Bicuspid Aortic Valve-Associated Aortopathy in Childhood: A Report From the MIBAVA Consortium.

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital heart defect affecting 1% to 2% of the population. It is associated with ascending aorta dilatation. Valve morphology, aortic stenosis (AS), and aortic insufficiency (AI) have been proposed as potential risk factors; however, evaluating their role is difficult, as these factors are inherently related. The aim of this study was to determine whether BAV morphology and dysfunction are independent determinants for ascending aorta dilatation in pediatric patients. METHODS: A multicenter, retrospective, cross-sectional study of pediatric BAV patients followed since 2004 was performed. Imaging data were assessed for BAV morphology, severity of AS and AI, history of coarctation, and aortic dimensions. Associations were determined using multivariable regression analysis. A subset of patients undergoing aortic interventions (balloon dilation or Ross) were assessed longitudinally. RESULTS: Data were obtained from 2122 patients (68% male; median age 10.2 years). Fifty percent of patients had ascending aorta dilatation. Right and noncoronary cusp fusion, increasing AS and AI, and older age were independently associated with ascending aorta dilatation. A history of coarctation was associated with less ascending aorta dilatation. In patients with neither AS nor AI, 37% had ascending aorta dilatation (4% severe). No complications related to aortic dilatation occurred in this cohort. Aortic Z scores were determined, and a Z-score calculator was created for this population. CONCLUSIONS: In this large pediatric cohort of patients with BAV, valve morphology, AS, and AI are independently associated with ascending aorta dilatation, suggesting that hemodynamic factors influence aortopathy. However, even in BAVs with no AS or AI, there is significant ascending aorta dilatation independent of valve morphology. Interventions that led to changes in degree of AI and AS did not seem to influence change in aortic dimensions. The current BAV cohort can be used as a reference group for expected changes in aortic dimensions during childhood.

Novel natural composite films as packaging materials with enhanced properties.

The present work was devoted to prepare novel natural composite films based on carboxymethyl cellulose (CMC), gelatin and/or shellac. Four composites films series were prepared by altering the film compositions from CMC and gelatin or shellac. The composite films were prepared by solution casting in presence of glycerol (30% weight). Films were characterized by SEM, air permeability (porosity), tensile strength, burst strength, TGA and WVP. Antimicrobial activity in opposition to E. coli, B. mycoides and C. albicans were also investigated. The results revealed that, films exhibit flexibility with good antimicrobial, tensile strength, homogeneity, transparency, elongation properties, reduce porosity & air permeability and without signs of particles aggregation. Gelatin/CMC (50/50%) film was the most important one with respect to thermal stability, which exhibit a high thermal stability up to 800 °C. This study opens the door to use cellulosic composite materials to produce environmentally friendly, low-cost and sustainable packaging materials.

Copy number variation analysis in bicuspid aortic valve-related aortopathy identifies TBX20 as a contributing gene.

Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD), affecting 1-2% of the population. BAV is associated with thoracic aortic aneurysms (TAAs). Deleterious copy number variations (CNVs) were found previously in up to 10% of CHD cases. This study aimed at unravelling the contribution of deleterious deletions or duplications in 95 unrelated BAV/TAA patients. Seven unique or rare CNVs were validated, harbouring protein-coding genes with a role in the cardiovascular system. Based on the presence of overlapping CNVs in patients with cardiovascular phenotypes in the DECIPHER database, the identification of similar CNVs in whole-exome sequencing data of 67 BAV/TAA patients and suggested topological domain involvement from Hi-C data, supportive evidence was obtained for two genes (DGCR6 and TBX20) of the seven initially validated CNVs. A rare variant burden analysis using next-generation sequencing data from 637 BAV/TAA patients was performed for these two candidate genes. This revealed a suggestive genetic role for TBX20 in BAV/TAA aetiology, further reinforced by segregation of a rare TBX20 variant with the phenotype within a BAV/TAA family. To conclude, our results do not confirm a significant contribution for deleterious CNVs in BAV/TAA as only one potentially pathogenic CNV (1.05%) was identified. We cannot exclude the possibility that BAV/TAA is occasionally attributed to causal CNVs though, or that certain CNVs act as genetic risk factors by creating a sensitised background for BAV/TAA. Finally, accumulative evidence for TBX20 involvement in BAV/TAA aetiology underlines the importance of this transcription factor in cardiovascular disease.

Bicuspid aortic valve related aortopathy.

Bicuspid aortic valve related aortopathy is known to significantly increase the risk for catastrophic aortic events and, therefore, represents a considerable health burden. Albeit of ongoing research in this field including genetic, molecular, hemodynamic and morphologic aspects, bicuspid aortic valve related aortopathy still represents an imperfectly understood disorder. This lack in knowledge results in a lack of consistency considering different therapeutic approaches. Recent studies have provided new insights into the etiology and clinical impacts of bicuspid aortic valve related aortopathy in different clinical settings, leading to a growing body of opinion towards a more individualized surgical approach than currently provided by the guidelines. Especially valvular hemodynamics-stenosis and regurgitation-seem to have significant impact on the development of bicuspid aortic valve related aortopathy. In this context, there is evidence that regurgitation of bicuspid aortic valves is the more fatal pathomechanism. Furthermore, "age" represents an aspect that should be taken into account when deciding whether to replace the aorta or not, because the diameter depends mainly on a patients age. The same diameter of the aorta in a 70-year old and a 20-year old patient has to be interpreted differently and should, therefore, result in different therapeutic strategies.

ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm.

Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1-2%)1-3 that frequently presents with ascending aortic aneurysm (AscAA)4. BAV/AscAA shows autosomal dominant inheritance with incomplete penetrance and male predominance. Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA5-8, impeding mechanistic insight and development of therapeutic strategies. Here, we report the identification of variants in ROBO4 (which encodes a factor known to contribute to endothelial performance) that segregate with disease in two families. Targeted sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with controls. Targeted silencing of ROBO4 or mutant ROBO4 expression in endothelial cell lines results in impaired barrier function and a synthetic repertoire suggestive of endothelial-to-mesenchymal transition. This is consistent with BAV/AscAA-associated findings in patients and in animal models deficient for ROBO4. These data identify a novel endothelial etiology for this common human disease phenotype.

Comparison of biomechanical properties in ascending aortic aneurysms of patients with congenital bicuspid aortic valve and Marfan syndrome.

BACKGROUND: In patients with ascending aortic aneurysms (AscAA), biomechanical differences are seen among patients with congenital bicuspid aortic valves (BAV), Marfan syndrome (MFS), and tricuspid aortic valves (TAV). We examined the hemodynamic profiles and ultrastructures of aneurysmal specimens, focusing on vascular remodelling to better understand AscAA pathogenesis. METHODS: A total of 795 patients with BAV (43.97 ±â€¯0.51 years; 93.2% male), 69 with MFS (34.43 ±â€¯1.44 years; 86.2% male), and 90 with TAV (67.27 ±â€¯0.58 years; 60% male) were enrolled, primarily upon admission with AscAA. The biomechanical properties of the aortic root were assessed and intraoperative specimens were analyzed by light-microscopy and two-photon autofluorescence microscopy. RESULTS: Patients with BAV had significantly greater distension of the aortic root, irrespective of age or aneurysmal widening (R2 = 0.543, p < 0.05). This was associated with significantly increase in the size of the tunica media. Patients with MFS displayed significant stiffness in the sinuses that worsened with age (R2 = 0.752, p < 0.001), similar to patients with TAV (R2 = 0.626, p < 0.05). Patients with MFS showed significant root elasticity with aneurysmal growth (R2 = 0.596, p < 0.05) and increased medial degeneration. Patients with TAV maintained biomechanical properties, apart from aneurysmal dimensions and high levels of inflammation. CONCLUSIONS: Among patients with AscAA, those with BAV maintain tissue elasticity in the aortic root, regardless of age. Patients with MFS demonstrate increased sinus stiffness with medial degeneration, both during aging and with aneurysmal growth. Patients with TAV and AscAA present with increased inflammation.

Imaging Mass Spectrometry for Characterization of Atrial Fibrillation Subtypes.

PURPOSE: Atrial fibrillation (AF) is a cardiac arrhythmia characterized by a rapid and irregular heart rhythm. AF types, paroxysmal (PX), persistent (PE), and long-lasting persistent (LSP), require differences in clinical management. Unfortunately, a significant proportion of AF patients are clinically misclassified. Therefore, the aim of this study is to prove that MALDI-Imaging (IMS) is valuable as a diagnostic aid in AF subtypes' assessment. EXPERIMENTAL DESIGN: Patients are clinically classified according to the guidelines of the European Society of Cardiology. FFPE tissue specimens from PE, PX, and LSP subtypes are analyzed by MALDI-IMS and evaluated by multi-statistical testing. Proteins are subsequently identified using LC-MS/MS and findings are confirmed by immunohistochemistry and through the determination of potential fibrosis via histopathology. RESULT: Determined that characteristic peptide signatures and peptide values facilitate to distinguish between PE, PX, and LSP arterial fibrillation subtypes. In particular, peptide values from alpha 1 type I collagen (CO1A1) are identified that are significantly higher in LSP and PE tissues but not in PX myocardial AF tissue. These findings are confirmed by immunohistochemistry and through the determination of potential fibrosis via histopathology. CONCLUSION AND RELEVANCE: These results represent an improvement in AF risk stratification by using MALDI-IMS as a promising approach for AF tissue assessment.

Carboxymethyl cellulose prepared from mesquite tree: New source for promising nanocomposite materials.

In the current article cellulose pulp extracted from mesquite tree was characterized and used as a raw material for preparation of carboxymethyl cellulose (CMC) which further used for preparing nanocomposite. CMC/Fe3O4 nanocomposite was synthesized by co-precipitation of iron (II) and (III) salts by aqueous ammonia in CMC solution. Cellulose pulp, CMC and CMC/Fe3O4 materials were characterized by using FTIR, XRD, TGA, SEM and TEM analysis. The results showed that homogenous spherical magnetic nanoparticles with diameter ∼25 nm were formed. The nanocomposite was further applied to remove methylene blue (MB) from aqueous solutions. The adsorption experiments showed the maximum adsorption capacity at pH 7. The adsorption results were analyzed by different isotherm and kinetic models and the results were fitted well with the Langmuir model and pseudo second-order model respectively. The current article showed that mesquite tree is a new resource for cellulose pulp which could be employed for preparing sustainable and environmentally friendly composite materials.

Corrigendum: Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor.

[This corrects the article on p. 400 in vol. 8, PMID: 28659821.].

Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor.

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter ≥ 4.0 cm in adults, or a Z-score ≥ 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype.

Synthesis of hybrid paper sheets with enhanced air barrier and antimicrobial properties for food packaging.

Paper sheets made from bagasse pulp have been modified using nanocellulose (NC) obtained from the same raw material. Modification of paper sheets have been carried out either through loading of paper with different concentrations of NC and antibacterial agent, Chitosan (Ch) during making sheets, or by surface coating of the paper. Crystals of NC extracted using concentrated sulfuric acid from bagasse pulp were found to have crystallinity index (CrI) 90%. Morphology of obtained NC has been confirmed by TEM and images revealed formation of NC crystals with large size distribution ranges from 4 to 60nm. Mechanical properties and air permeability of paper sheets loaded with different ratios of NC and Ch have been investigated. The results showed that presence of NC did not negatively affect the obtained modified paper sheets, while air permeability decreased with adding 8% NC to paper matrix. On the other hand, surface coverage of paper sheets with NC greatly reduced air permeability. Antimicrobial investigations carried out by optical density method indicated that presence of Ch in the paper sheets as an additive or in a coating formulation enhanced paper resistance to different microorganisms especially those causing food poisoning. The current study confirms that the modified paper can have potential application in food packaging.

Erratum: Lazar-Karsten, P., et al. Generation and Characterization of Vascular Smooth Muscle Cell Lines Derived from a Patient with a Bicuspid Aortic Valve. Cells 2016, 5, 19.

The authors wish to make the following erratum to this paper [1].[...].