Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.     

The Rational Use of Water Resources in the Strategy of Industry 4.0

The article substantiates that the transformation of the world economy associated with Industry 4.0 leads to a significant change in the way resources are used and affects the possibility of implementing the concept of sustainable development. In this regard, a combined analysis of the concept of new industrial development and the concept of sustainable development, as well as an assessment of the current practice of their implementation is required. In this paper, such an analysis was carried out on the example of water resources management. The paper proposes a methodology for assessing the correlation of water management and industrial development levels of regions. This includes the use of both traditional statistical approaches to the analysis of the level of development of economic systems, and elements of data mining. The neural network is constructed in order to estimate the forecasted values of the water intensity of the gross regional product when the indicators of the level of industrial development of the regions change. The results show that the most significant indicators for changing water intensity include advanced production technologies used, the share of value-added to high-tech industries, and innovative activities of organisations.

     

Synergistic and suppressive effects of dietary phenolic acids and other phytochemicals from cereal extracts on nuclear factor kappa B activity

In this study the combinatorial action of the main phenolic acids (ferulic, caffeic, p-coumaric and sinapic acids) found in extracts of free (ME) and bound phenolic acids (HE) from oat, barley and wheat flour on the modulation of NF-κB activity was investigated. The results show that combination of phenolic acids in low concentrations (<0.1 μg/ml) has a significant synergistic, or enhanced effect, on NF-κB activity, while their combination in high concentrations (0.3–70 μg/ml) helps to suppress the strong effect obtained by individual solutions of ferulic and p-coumaric acids. The modulation of NF-κB activity observed by HE extracts is the effect of combinatorial action of the phenolic acids present therein, while the modulation of NF-κB activity observed with ME extracts is the result of combinatorial action of phenolic acids together with other phenolic compounds present in the extracts. These results increase the knowledge about the health promoting effect from cereal consumption and dietary phenolic acids.     

Brewer’s spent grain as a functional ingredient for breadsticks

Brewer’s spent grain (BSG) was evaluated for its potential as a functional baking ingredient. Scanning electron microscopy (SEM) was used to examine the microstructure of BSG and wheat flours. Baked snacks (breadsticks) were prepared using 15%, 25% and 35% BSG and evaluated for their baking quality and fibre and protein content (over a period of 3 months). The addition of BSG altered the baking characteristics of the breadsticks by affecting their structure and texture. The snacks appeared to lack in cellular structure and crispiness. However, they had quite a stable shelf‐life, as changes in texture, moisture and a_w progressed at a low rate. Addition of 25% and 35% BSG significantly increased the protein content of the snacks, and addition of 15% BSG more than doubled the content of dietary fibre in the samples.     

Serum and urine metal levels in patients with metal-on-metal surface arthroplasty

The resurgence of metal-on-metal articulating surfaces for hip arthroplasty has also heightened concerns about the degree and magnitude of metal particle generation and the accompanying increase in circulating metal ion concentrations. In this study, we measured the concentration of chromium in serum and urine and the concentration of cobalt in serum in twenty-five patients with modern metal-on-metal surface arthroplasty of the hip in a prospective manner. The results showed that the mean post-operative chromium in serum levels were 22-fold, 23-fold and 21-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative cobalt in serum levels were 8-fold, 7-fold and 6-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative chromium in urine levels were 9-fold, 10-fold and 14-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The values seen in this study with the current generation of surface arthroplasties are: (a) lower than those seen in an earlier generation of surface arthroplasties; (b) in the same range as those observed in association with metal-on-metal conventional total hip replacements, which typically have smaller head sizes; (c) higher than values observed in patients with conventional metal-on-polyethylene articulating couples.     

The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

To investigate the effect of leptin in childhood ITP, we measured plasma leptin in 39 children with acute ITP, after treatment and in remission, and in 33 healthy age/BMI-matched controls. We also cultured ITP and control peripheral blood mononuclear cells (PBMCs) with recombinant leptin to assess its direct effect on pro/anti-inflammatory cytokine gene expression. A significant increase in leptin was observed in children with active disease compared to controls. A significant inverse correlation of leptin with platelet count was also observed in children with acute ITP. Leptin remained high after treatment with IVIg, whereas steroid treatment lowered leptin below control levels. In remission, leptin was in the control range. Cytokine gene expression was significantly increased in children with acute ITP compared with controls, with highest expression for IFN-γ and IL-10. IVIg/steroid treatment significantly decreased IFN-γ and IL-10 expression. In remission, IFN-γ and IL-10 expression remained low. Addition of leptin to PBMCs isolated from patients in remission resulted in a significant increase in IL-10 gene expression compared to controls. Further experiments with purified T-cells and monocytes identified monocytes as the source of leptin-induced IL-10. We suggest that leptin acts as an active anti-inflammatory agent in childhood ITP by promoting IL-10 secretion by monocytes.     

Natural Silk Film for Magnesium Protection: Hydrophobic/Hydrophilic Interaction and Self‐Healing Effect

Biodegradable implants are required in order to provide successful treatment of injuries. Temporary magnesium‐based implants with particular properties are needed in cases when it is desirable not only to maintain vital activity, but also to initiate the self‐healing process of damaged bones or tissues as well. Unfortunately, the use of magnesium alloys is limited due to the fast biodegradability of the applied material. The aim of this research is to improve the corrosion resistance of magnesium alloys by sonochemical treatment in silk solution followed by additional layer‐by‐layer deposition of natural silk on the magnesium surface. The sonication process is carried out at a frequency of 20 kHz during 5–10 min, while the duration of the silk layer deposition is 15 min. The corrosion behavior of magnesium substrates modified by natural silk layer‐by‐layer assembly is studied. Magnesium substrates sonochemically treated in silk solution demonstrate three times better corrosion resistance compared to control samples sonochemically treated in water. Additional deposition of a silk layer enhances obtained corrosion resistance by 18 times, resulting in a 54‐fold increase overall.     

Performance of New Biodegradable Di‐Sulfonate Surfactants as Hydrotropes in High‐Temperature and Salinity Environments

Propyl alkyl ether sulfonate (PAES) surfactants, recently developed by The Dow Chemical Company, show excellent electrolyte, hard water and caustic solubility, with attractive ECOTOX profile and biodegradability. Due to their unique structure and properties, they are good candidates for use as hydrotropes in formulations containing nonionic surfactants. The goal of these studies was to evaluate hydrotropic efficiency of PAES materials via cloud point analysis. The effects of PAES alkyl tail length, concentration, and mono‐ and di‐sulfonate components on the cloud point of TERGITOL? 15‐S‐9 in solutions of varying electrolyte strength were investigated. In the presence of high electrolyte levels, PAES 12C had the highest hydrotropic efficiency of all materials tested, including commonly used commercial hydrotropes. Di‐sulfonate components of the PAES materials were found to be more efficient hydrotropes than mono‐sulfonate in high electrolyte environments for all tail lengths tested. The di/mono ratio and tail length were found to be critical parameters.