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We report a novel HLA‐B*58 allele, now named B*58:141, identified by next‐generation sequencing. [ABSTRACT FROM AUTHOR]

The development and progression of colorectal cancer (CRC) have been associated with inflammation processes that involve the overactivation of the NF‐κB signalling pathway. The characterization of the NF‐κB expression profile in CRC is an important topic since the suppression of NF‐κB represents a potential therapeutic approach. In this study, we assessed the expression levels of 84 NF‐κB‐related genes in paired tumoral (T) and peritumoral (PT) tissues from 18 CRC patients and 18 normal colonic mucosae, and the expression levels of three miRNAs targeting the most dysregulated genes revealed by the case–control analysis. Comparing the gene expression profile of T and controls, 60 genes were dysregulated. The comparison of T and PT revealed 17 dysregulated genes in the tumoral tissues, with IL1B, CXCL8, IL1A, and CSF2 being the most upregulated. Notably, through a bioinformatics analysis, the differential gene expression of 11 out of the 17 genes was validated on a larger cohort of 308 CRC patients compared with 41 controls. Moreover, a decrease in the levels of RELA, NOD1, CASP8, BCL2L1, ELK1, and IKBKB was identified in poorly differentiated tumours compared to moderately differentiated tumours. The analysis of the three miRNAs targeting IL1B, CXCL8, IL1A, and CSF2 showed that miR‐182‐5p was upregulated in T compared with PT, whereas miR‐10b‐5p was downregulated in T compared with PT and control tissues. Our results may contribute to the design of new experimental therapeutic strategies based on endogenous molecules, such as miRNAs, to target the genetic key players of the NF‐ κB pathway. [ABSTRACT FROM AUTHOR]

Objectives: The SARS‐CoV‐2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3‐dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs). Methods: We analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated‐omicron variant in 113 SOTRs, of whom 44 had recovered from COVID‐19 (recovered‐SOTRs) and 69 had not contracted the virus (COVID‐naïve). In addition, 30 HCs, 8 of whom had recovered from COVID‐19, were also studied. Results: Here, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti‐viral antibodies against all viral strains in the fully vaccinated COVID‐naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti‐RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered‐SOTRs who received two doses of vaccine demonstrated both higher anti‐RBD IgG levels and neutralizing activities against all VOC, including omicron. Conclusion: These findings illustrate a significant impact of previous infection on the development of anti‐SARS‐CoV‐2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser‐vaccine responsive population. [ABSTRACT FROM AUTHOR]

Pyruvate, the end product of glycolysis, is a key metabolic molecule enabling mitochondrial adenosine triphosphate synthesis and takes part in multiple biosynthetic pathways within mitochondria. The mitochondrial pyruvate carrier (MPC) plays a vital role in transporting pyruvate from the cytosol into the organelle. In humans, MPC is a hetero‐oligomeric complex formed by the MPC1 and MPC2 paralogs that are both necessary to stabilize each other and form a functional MPC. MPC deficiency (OMIM#614741) due to pathogenic MPC1 variants is a rare autosomal recessive disease involving developmental delay, microcephaly, growth failure, and increased serum lactate and pyruvate. To date, two MPC1 variants in four cases have been reported, though only one with a detailed clinical description. Herein, we report three novel pathogenic MPC1 variants in six patients from three unrelated families, identified within European, Kuwaiti, and Chinese mitochondrial disease patient cohorts, one of whom presented as a Leigh‐like syndrome. Functional analysis in primary fibroblasts from the patients revealed decreased expression of MPC1 and MPC2. We rescued pyruvate‐driven oxygen consumption rate in patient's fibroblasts by reconstituting with wild‐type MPC1. Complementing homozygous MPC1 mutant cDNA with CRISPR‐deleted MPC1 C2C12 cells verified the mechanism of variants: unstable MPC complex or ablated pyruvate uptake activity. Furthermore, we showed that glutamine and beta‐hydroxybutyrate were alternative substrates to maintain mitochondrial respiration when cells lack pyruvate. In conclusion, we expand the clinical phenotypes and genotypes associated with MPC deficiency, with our studies revealing glutamine as a potential therapy for MPC deficiency. [ABSTRACT FROM AUTHOR]

The bioclimatology of thermal stress over Europe between 1979 and 2019 was analysed using the Universal Thermal Climate Index (UTCI) derived from ERA5‐HEAT reanalysis. The bioclimatology of different European regions was assessed using Köppen–Geiger climate classification. The annual number of hours with heat stress (UTCI > 32°C) increased significantly during the study period for all the analysed Köppen–Geiger climate subclasses, showing also a clear increase towards southern Europe. The highest percentage of hours (20% of all hours) with cold stress (UTCI < −13°C) occur over northern Europe. A significant increasing trend (>0.05 hr·year−1) in the number of hours with heat stress was observed for 23 out of 32 analysed European cities representative for the Köppen–Geiger climate subclasses. For these cities not only the number of hours with heat stress has increased but also the heat stress is more persistent, while the number of cases and the persistence of the periods with cold stress have decreased over the last four decades. The UTCI values showed a statistically significant increase between 0.6 and 3.2°C for all the analysed cities over the study period reflecting the rising of global mean temperatures. [ABSTRACT FROM AUTHOR]

Aims: Allograft rejection following heart transplantation (HTx) is a serious complication even in the era of modern immunosuppressive regimens and causes up to a third of early deaths after HTx. Allograft rejection is mediated by a cascade of immune mechanisms leading to acute cellular rejection (ACR) and/or antibody‐mediated rejection (AMR). The gold standard for monitoring allograft rejection is invasive endomyocardial biopsy that exposes patients to complications. Little is known about the potential of circulating miRNAs as biomarkers to detect cardiac allograft rejection. We here present a systematic analysis of circulating miRNAs as biomarkers and predictors for allograft rejection after HTx using next‐generation small RNA sequencing. Methods and results: We used next‐generation small RNA sequencing to investigate circulating miRNAs among HTx recipients (10 healthy controls, 10 heart failure patients, 13 ACR, and 10 AMR). MiRNA profiling was performed at different time points before, during, and after resolution of the rejection episode. We found three miRNAs with significantly increased serum levels in patients with biopsy‐proven cardiac rejection when compared with patients without rejection: hsa‐miR‐139‐5p, hsa‐miR‐151a‐5p, and hsa‐miR‐186‐5p. We identified miRNAs that may serve as potential predictors for the subsequent development of ACR: hsa‐miR‐29c‐3p (ACR) and hsa‐miR‐486‐5p (AMR). Overall, hsa‐miR‐486‐5p was most strongly associated with acute rejection episodes. Conclusions: Monitoring cardiac allograft rejection using circulating miRNAs might represent an alternative strategy to invasive endomyocardial biopsy. [ABSTRACT FROM AUTHOR]

This study is aimed at investigating tumoral and inflammatory cells and the significance of the prognostic factors of pancreatic ductal adenocarcinoma (PDAC); it is also aimed at determining the role of immunohistochemistry in the diagnosis and prognosis of this neoplasm. Materials and Methods. 230 cases of pancreatic ductal adenocarcinoma were included in the study group; these cases were selected from the archives of the Department of Pathology of the Fundeni Clinical Institute over a ten-year period. Immunohistochemistry was performed using the following antibodies: MUC 1, CD 34, Factor VIII, CD 68, MMP-7, CEA, p21, p53, and Ki 67. Results. There were 133 male (57.8%) and 97 female (42.2%) patients included in this study, with ages between 20 and 81 years old (mean age: 58.2 years) and with tumors located in the pancreatic head (n = 196; 85.2%), pancreatic body (n = 12; 5.2%), and pancreatic tail (n = 20, 8.7%), as well as panpancreatic tumors (n = 2; 0.9%). Patients presented with early stages (IA and IB), with low pathologic grade (G1), with small size tumors (less than 1-1.5 cm), with tumors located in the head of the pancreas, (p53: negative; p21: positive; and CD 68: positive in peritumoral tissue), with low nuclear index (Ki 67 < 10%), without metastases at the time of surgery (had a better prognosis), and with a survival rate of about 7 months. Conclusions. Immunohistochemistry is useful for an accurate diagnosis, differential diagnosis, and establishment of additional factors that might have a prognostic importance. It is recommended to study peritumoral tissue from the quantitative and qualitative points of view to increase the number of prognostic factors. This study represents a multidisciplinary approach, and it is a result of teamwork; it presents histopathological methods of examination of this severe illness and describes only a part of the scientific effort to determine the main pathological mechanisms of this neoplasm. [ABSTRACT FROM AUTHOR]

Background: Hereditary spherocytosis (HS) is a common inherited disease affecting the erythrocyte membrane. Total splenectomy (TS) is effective in reducing hemolysis and decreasing the need of transfusions, but total removal of the spleen represents a potential risk factor for infectious and non-infectious complications. On the other hand, subtotal splenectomy (STS) could be an alternative therapy for HS. The aim of this study is to establish which surgical approach has the best outcome in HS. Methods: All patients (n = 63) receiving splenectomy for HS between 2002 and 2016 from one institution were retrospectively reviewed. Hemoglobin and reticulocytes levels during preoperative and postoperative follow-up periods were compared. Additionally, a meta-analysis was performed analyzing data regarding hemoglobin and reticulocytes levels from several available studies. Result: At 1-year follow-up, our clinical data showed that mean hemoglobin levels increased after TS from (mean ± SD) 9.77 ± 1.82 to 11.88 ± 2.08 g/dl, while after STS from 8.98 ± 1.66 to 11.87 ± 1.38 g/dl. At 3-year and 5-year follow-up after TS, we observed an increase from 9.77 ± 1.82 to 13.59 ± 2.03 and 13.46 ± 1.64 g/dl, respectively. At 3-year and 5-year follow-up after STS in our cohort, we observed an increase from 8.98 ± 1.66 to 13.21 ± 1.95 and 13.68 ± 1.65 g/dl, respectively. The meta-analysis (for a follow-up period of 1 year) showed that the hemoglobin levels increased with 2.61 g/dl (95% CI 2.15–3.08 g/dl; p < 0.001) after TS, and with 1.67 g/dl (95% CI 1.25–2.10 g/dl; p < 0.001) after STS. Conclusion: We conclude that subtotal and minimally invasive splenectomy could be considered as the first line of treatment in severe HS cases, especially in children. [ABSTRACT FROM AUTHOR]

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non‐infectious complications, with unknown mechanisms. In order to explore the role of the non‐coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR‐223 was overexpressed immediately and late after splenectomy, while miR‐146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR‐16, miR‐93, miR‐26a and miR‐26b were overexpressed only late after splenectomy, suggesting similarities with sepsis. We also explored the non‐coding (nc)RNome of circulating peripheral blood leucocytes by performing a ncRNA full genome profiling. We observed a reorganization of the ncRNoma after splenectomy, characterized by up‐regulation of miRNAs and down‐regulation of transcribed pyknons (T‐PYKs). Pathway analysis revealed that deregulated miRNAs control pathways involved in immunity, cancer and endothelial growth. We checked the expression of the ncRNAs in 15 immune cell types from healthy donors and observed that plasma miRNAs, cellular miRNAs and T‐PYKs have a cell‐specific expression pattern and are abundant in different types of immune cells. These findings suggest that the ncRNAs potentially regulate the immune changes observed after splenectomy. [ABSTRACT FROM AUTHOR]

In this work we investigate the performance of a simple, disposable electrochemical aptasensor for lysozyme and its usefulness for monitoring the allergen risk along wine production. The sensor relies on screen‐printed gold electrodes modified with gold nanoparticles as the electrochemical transducer, with detection by cyclic voltammetry. This simple method is characterized by a detection limit of 0.32 μg.mL−1 lysozyme and a linear range of 1–10 μg.mL−1, being appropriate for the analysis of lysozyme‐treated wines. Several white wines where sulphur dioxide was partially replaced by lysozyme were produced and analyzed with the aptasensor at critical stages during wine production. The results obtained with the aptasensor were moreover compared with those recorded in parallel by a standard method, high performance liquid chromatography (HPLC). The specific advantages brought by the use of nanomaterial and the limitations of the sensor are discussed. The sensor allowed evaluating the effect of various technological steps along wine production on the content of lysozyme. [ABSTRACT FROM AUTHOR]

To enhance their longevity, dental implants must be highly biocompatible and must have a low elastic modulus close to that of the bone. They must also possess a high superficial hardness and a high corrosion resistance. For these reasons, a recently developed low‐modulus Ti–27Nb alloy with nontoxic elements was treated by gas nitriding at high temperature in this study. A very thin nitrided layer of 0.5 μm in thickness followed by an enriched nitrogen zone was observed. Consequently, a very high hardness evaluated at about 1800 HV was obtained in surface, which represents an increase of 4–5 times the hardness of the non‐nitrided alloy. This superficial hardness was experimentally observed to decrease up to 800 nm in depth from the surface to the core. The low modulus of Ti–27Nb (evaluated at 55 GPa, which is twice lower than the commercially pure titanium) was not affected by the surface nitriding treatment. A better corrosion resistance was observed and a significant decrease in ion release rates for the nitrided alloy (ion release of 1.41 ng/cm2 compared to the 163.58 ng/cm2 obtained for the commercially pure titanium at pH = 7.48 in artificial Carter–Brugirard saliva). The cytocompatibility was not compromised and the cell viability performed on human osteoblasts, fibroblastic cells, and epithelial cells was enhanced on the nitrided surface in comparison with the non‐nitrided surface. These combined properties make the nitrided Ti–27Nb alloy a good candidate for dental implant applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1483–1490, 2019. [ABSTRACT FROM AUTHOR]

In this paper, the microstructure, mechanical and anticorrosive properties of the new CoCrNbMoZr alloy were studied in comparison with those of the commercial CoCrMo, Heraenium CE alloy. SEM and XRD techniques were used to evince the microstructure, and the morphology of the two alloys. Electrochemical linear and potentiodynamic polarisation and electrochemical impedance spectroscopy methods showed the electrochemical and corrosion behaviour of the alloys in artificial Carter-Brugirard saliva of different composition (doped with NaF, pH=8.21 and undoped) and pH values (3.83; 7.84; 9.11) simulating the various functional conditions from the oral cavity. The new CoCrNbMoZr alloy showed self-passivation, more favourable values of the corrosion, passivation and transpassive potentials and tendency to passivation than those of the commercial Heraenium CE alloy and lower values of the passive current density; the values of the corrosion current densities and corrosion rates are lower and polarisation resistances are higher comparing with those of the reference alloy. EIS spectra revealed a passive film, a compact, resistant layer formed especially by the chromium, cobalt, niobium and zirconium oxides. Taking into consideration the microstructural features, electrochemical behaviour, corrosion resistance, and mechanical characteristics, it results that the new CoCrNbMoZr alloy is recommended for the dental applications. [ABSTRACT FROM AUTHOR]

Starting as a therapeutically option for high-risk surgical patients with degenerative aortic valve stenosis, the transcatheter aortic valve implantation method is probably going to become the method of choice for this pathology also in younger and low-risk patients. As bioprosthesis are prone to degeneration, requiring a redo procedure, whenever a valve in valve procedure is contraindicated, a surgical valve replacement will become necessary. We describe a simple surgical method for explantation of a Sapien XT prosthesis that was implanted 7 years previously in a calcified aortic valve. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is to assess the impact of the splenic hilar vasculature configuration on the amount of remnant splenic parenchyma volume after partial splenectomy for splenic cysts.Methods: The data of all patients receiving a splenectomy for a splenic cyst from 2002 to 2016 at the Center of General Surgery and Liver Transplantation of Fundeni Clinical Institute were retrospectively reviewed. The size and location in the splenic parenchyma of the cyst and the splenic hilar vasculature type were assessed for each patient with a splenectomy.Results: Thirty-one patients with non-parasitic and 32 patients with hydatid cysts were recorded. In cases of centrally located cysts, a total splenectomy was performed for the majority of cases, while in peripheral cysts a spleen-preserving surgery was feasible for most of the patients (p = 0.001). The size of the cyst was significantly higher in the group of patients with a total splenectomy, compared with the group with a partial splenectomy (p = 0.003). In the subgroup with a distributed arterial pattern, preservation of more than 50% of the initial parenchyma was achieved in a significantly higher proportion of patients, compared with the subgroup of patients with a magistral pattern (p = 0.012).Conclusion: Besides cyst size or peripheral location in the splenic parenchyma, the vascular pattern is also considered another decisive factor that associates with successful conservative or minimally invasive approach. [ABSTRACT FROM AUTHOR]

Nanomaterials used in tandem with electrochemical mediators on screen‐printed electrodes enable sensitive, low cost detection of NADH with minimal interferences in real‐world samples. In this work we investigated the combination between the mediator Meldola Blue and several types of commercial screen‐printed carbon electrodes, i. e. modified with mesoporous carbon, single wall carbon nanotubes, graphene or carbon nanofibers (CNF) as NADH detectors. The sensors were compared with bare carbon electrodes and with commercially available Meldola Blue‐modified electrodes. The best sensitivity for NADH detection by amperometry was observed for Meldola Blue/CNF electrodes, and further improvement was obtained by mixing the mediator with graphene oxide prior to dropcasting. The "MB‐erGO/CNF" sensors obtained were characterized by a detection limit of 0.5 μM, a linear range of 1–300 μM and a sensitivity of 80.0±2.5 μA cm−2 mmol−1 L, 10 times higher than that of commercial sensors. While the use of graphene oxide lead to enhanced sensitivity and wider linear range, it didn't improve the operational stability as the mediator gradually desorbed from the electrodes. Furthermore, the sensors were coupled with a new NAD+‐dependent aldehyde dehydrogenase from a psychrophilic bacterium for the analysis of benzaldehyde and proven to be advantageous over commercial electrodes with Meldola Blue in circumstances where the detection was limited by NADH detection, i. e. at pH 9.5. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of poly(tartronic‐co‐glycolic acid) from tartronic acid is achieved by a simple thermal polycondensation method. This novel polyester was characterized by NMR and Fourier transform infrared spectroscopy as well as by high‐resolution electrospray ionization mass spectrometry. It contains pendent carboxyl groups at the tartronic acid units which therefore render it a more hydrophilic and more versatile analogue of poly(glycolic acid) combining the known biodegradability with the functionality of the pendent carboxyl groups. Thus, it is of interest for application in the synthesis of drug‐carrying biodegradable matrices. The copolymer was further used for coating different surfaces of magnetic nanoparticles such as magnetite, silica, titanium dioxide and exploited as a platform for further functionalization. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Abstract: Aim: To review the published studies that dose down and then discontinue biologic therapy in patients with rheumatoid arthritis (RA), particularly concerning the criteria for such dosing and the impact on clinical outcomes. Methods: Published studies conducted in patients with RA that sequentially decreased the dose and then discontinued therapy were included if one or more of the following biologic disease modifying antirheumatic drugs (bDMARDs) was evaluated: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab or tocilizumab. Results: Five studies qualified for inclusion. The populations of patients with RA were heterogeneous among the studies; patients were required to have low disease activity (LDA) or to be in remission prior to dose titration. Approximately 25–65% of patients successfully decreased and in some cases, discontinued the bDMARD. However, the flare rate was higher than for the patients who remained on a standard dose. The only variable that predicted relapse in more than one study was down‐titration of the bDMARD dose. Conclusion: In patients who have achieved LDA or remission, down‐titration and discontinuation of bDMARD therapy may be attempted, with careful monitoring. However, it is likely that some patients will flare, and it is not known how to predict these patients. [ABSTRACT FROM AUTHOR]

The new Ti-15Ta-5Zr alloy revealed a homogeneous bi-phase α + β microstructure without inclusions or secondary phases. The alloy native passive film contains both Ti2O3, and TiO2 oxides and very resistant Ta2O5 and ZrO2 oxides (X-ray photoelectron spectroscopy). All main electrochemical and corrosion parameters in artificial Carter-Brugirard saliva had more favourable values than those of Ti and other implant alloys, due to the Ta and Zr alloying elements, which contributed with their protective oxides to the native passive film and due to the alloy very homogeneous microstructure. Impedance spectra indicated a passive film formed by two layers: an inner, insulating, barrier layer that provides the high corrosion resistance and an outer, porous, less protective layer that permits the absorption of ions and species from surrounding environment into its pores, favouring both interaction and bioactivity. X-ray photoelectron spectroscopy and scanning electron microscopy detected new depositions (Na3PO4 and K3PO4 protective compounds) of 5 nm thickness on the alloy surface after 1000 h in Carter-Brugirard saliva, which confer to the substrate both corrosion resistance and bioactivity. [ABSTRACT FROM AUTHOR]

In the present work, nitrogen ion implantation (original method) to enhance the corrosion performance and cytocompatibility of biomedical pure titanium (CP Ti) and Ti-6Al-4V alloy has been studied. Different characterization methods were used to investigate the corrosion resistance of the nitrided Ti and Ti-6Al-4V samples such as anodic polarization, electrochemical impedance spectroscopy, monitoring of the open circuit potentials and corresponding gradients, evaluation of corrosion rates. Further, cell viability, initial cell spreading and osteoblast proliferation were tested in order to assess cytocompatibility of modified Ti and Ti-6Al-4V alloy. In severe functional conditions, the main electrochemical parameters for nitrided biomaterials presented better values, revealing nobler behaviour than un-nitrided samples; these more favourable values assure a very good corrosion resistance for long term of the treated biomaterials. The results of biological performance evaluation indicated that nitrided Ti and Ti-6Al-4V represent suitable biomaterials for the adhesion and proliferation of human osteoblasts in vitro. All these findings demonstrate that nitrided biomaterials exhibited a very good improvement of their corrosion resistance and biocompatibility, characteristics which recommend them as potential candidates for bone implants. [ABSTRACT FROM AUTHOR]

Abstract: Electrochemical aptasensors appear as promising tools in food analysis, able to provide sensitive, fast and cost‐effective analysis, with the added advantage of portability. Carbon nanomaterials and in particular carbon nanotubes and graphene are among the nanomaterials most often used to build electrochemical aptasensors due to their good electrical conductivity, large surface area and multiple functionalisation possibilities. This review aims to give an overview of the types of carbon nanomaterials and their composites which have been used to enhance the performance of electrochemical aptasensors. Examples are detailed for the biosensors which were tested with real food samples. In these aptasensors, carbon nanomaterials have played different roles, from facilitating the immobilization of high amounts of aptamer and enhancing the electroactive area of the sensors to roles as nanocarrier for signaling probes in amplification schemes or even as electroactive probes generating the output signal. The survey of recent literature shows a positive evolution towards increased aptasensor testing with food samples. However, many challenges remain related to the better characterization of nanomaterials used, clarifying the roles of specific components in multi‐component nanocomposites and widening the types of food matrices and analytes tested with the aptasensors. Although we are still far from knowing when these novel tools will replace classic analytical methods in food analysis, carbon nanomaterials will certainly continue to play an important role in the design of future electrochemical aptasensors for food analysis. [ABSTRACT FROM AUTHOR]

In this work, the new (Ti-Zr)-1.5Mo-3Sn biomedical alloy showing a large superelastic recovery strain of 7% and Young's modulus of 60 GPa was characterized and compared with CP Ti and Ti-6Al-4V alloys currently used in medicine. The microstructure of the new (Ti-Zr)-1.5Mo-3Sn alloy consists of single β phase (XRD and optical microscopy results). The new alloy has a relatively thick (7.0 nm) native passive film mainly formed by protective TiO2, ZrO2, MoO2, and SnO2 oxides (XPS data). The electrochemical parameters for the new alloy have more favorable values than those of CP Ti, and Ti-6A-4V alloy, namely a nobler electrochemical behavior. The corrosion current density and rate of the (Ti-Zr)-1.5Mo-3Sn alloy are about 7 times lower and the polarization resistance is about 5 times higher than those obtained for the comparing metallic biomedical materials. Electrochemical impedance spectra proved that the new alloy presents the most insulating and protective passive film out of the three studied materials. [ABSTRACT FROM AUTHOR]

In this work, a new ternary Ti-25Ta-5Zr alloy (with nontoxic alloying elements) was obtained and used to develop a thermo-mechanical procedure in order to optimize the balance strength - elastic modulus. Data about structural (by SEM) and mechanical properties are investigated. Also, its electrochemical behaviour in Ringer-Brown and Ringer solutions of different pH values (simulating severe functional conditions of an implant) was studied by cyclic potentiodynamic and linear polarization and electrochemical impedance spectroscopy (EIS). From cyclic potentiodynamic polarization curves it resulted the nobler behaviour of the thermo-mechanical treated alloy than as-cast alloy due to the favourable influence of the applied processing. Impedance spectra were fitted with one time constant equivalent circuit characterizing a very stable, resistant oxide passive film. The values of the open circuit potentials for the treated alloy are nobler than of the as-cast alloy and tended to more positive values in time, proving that the passive film on its surface is more compact and thickened in time. [ABSTRACT FROM AUTHOR]

A new Ti-20 Nb-10 Zr-5 Ta bioalloy with low Young's modulus (59 GPa) was coated with nanocrystalline hydroxyapatite ( HA) ceramic layer by chemical method of soaking in a slightly supersaturated calcium and phosphate ions solution. The formation of HA was demonstrated using XRD, Raman microscopy and energy-dispersive X-ray spectroscopy; the coating morphology and microstructure were determined using SEM. The coating protective capacity and its long-term (2000 h) stability in simulated biofluids were revealed by the improvement of the all electrochemical parameters; also, HA ceramic coating reduced the alloy corrosion and ion release rates. After 2000 immersion hours in biofluids no compositional change occurs in the HA ceramic coating, only depositions from solution take place that change the coating morphology. Also, the in time increase of the coating stability and thickness (as a result of the new deposition from physiological solutions) indicates bioactivity. [ABSTRACT FROM AUTHOR]

The properties of the surface films formed on Ti and its Ti-5Al-4V and Ti-6Al-3.5Fe alloys by chemical (immersion in 10 M NaOH) and thermal treatment (500 °C) were studied in this paper. Their corrosion behaviour in Ringer solution was investigated. After treatments, the sample microhardness was measured. Also, the sample surfaces were observed by an optical microscope before and after immersion in Ringer solutions. The electrochemical behaviour of the surface films obtained by the chemical and thermal treatments was studied using the methods of the electrochemical impedance spectroscopy (EIS) and monitoring of open circuit potentials at different immersion periods (up to 60 days) in Ringer solution. Microhardness increased with the increasing loads for the studied materials, showing the existence of a compact protective layer. Microscopic observations exhibited more compact coatings after 60 days of exposure in Ringer solution, due to the formation of an apatite layer. EIS spectra revealed surface films with two layers: an inner, barrier protective layer and an outer, porous apatite layer. The impedance increases in time denoting that the films have grown by apatite nucleation. Also, EIS spectra showed that the complex treatment by chemical + heat method is the most efficiently. For the samples treated by the two processes (chemical + heat) the values of the open circuit potentials are nobler than of the chemical treated samples, denoting better protective, bioactive films. [ABSTRACT FROM AUTHOR]

We report a 10-year-old girl presenting with severe neonatal hypertrophic cardiomyopathy (HCM), feeding difficulties, mildly abnormal facial features, and progressive skeletal muscle symptoms but with normal cognitive development. Targeted oligonucleotide-selective sequencing of 101 cardiomyopathy genes revealed the genetic diagnosis, and the mutation was verified by Sanger sequencing in the patient and her parents. To offer insights into the potential mechanism of patient mutation, protein structural analysis was performed using the resolved structure of human activated HRAS protein with bound GTP analogue (PDB id 5P21) in Discovery Studio 4.5 (Dassault Systèmes Biovia, San Diego, CA). The patient with hypertrophic cardiomyopathy and normal cognitive development was diagnosed with an HRAS mutation c.173C>T (p.T58I), a milder variant of Costello syndrome affecting a highly conserved amino acid, threonine 58. Our analysis suggests that the p.G12 mutations slow GTP hydrolysis rendering HRAS unresponsive to GTPase activating proteins, and resulting in permanently active state. The p.T58I mutation likely affects binding of guanidine-nucleotide-exchange factors, thereby promoting the active state but also allowing for slow inactivation. Patients with the HRAS mutation c.173C>T (p.T58I) might go undiagnosed because of the milder phenotype compared with other mutations causing Costello syndrome. We expand the clinical and molecular picture of the rare HRAS mutation by reporting the first case in Europe and the fourth case in the literature. Our protein structure analysis offers insights into the mechanism of the mildly activating p.T58I mutation. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The influence of gas nitriding surface treatment on the superelastic Ti-23Nb-0.7Ta-2Zr-0.5N alloy was evaluated. A thorough characterization of bare and nitrided Ti-based alloy and pure Ti was performed in terms of surface film composition and morphology, electrochemical behaviour, and short term osteoblast response. XPS analysis showed that the nitriding treatment strongly influenced the composition (nitrides and oxynitrides) and surface properties both of the substrate and of the bulk alloy. SEM images revealed that the nitrided surface appears as a similar dotted pattern caused by the formation of N-rich domains coexisting with less nitrided domains,while before treatment only topographical features could be observed. All the electrochemical results confirmed the high chemical stability of the nitride and oxynitride coating and the superiority of the applied treatment. The values of the corrosion parameters ascertained the excellent corrosion resistance of the coated alloy in the real functional conditions fromthe human body. Cell culture experiments with MG63 osteoblasts demonstrated that the studied biomaterials do not elicit any toxic effects and support cell adhesion and enhanced cell proliferation. Altogether, these data indicate that the nitrided Ti-23Nb-0.7Ta-2Zr-0.5N alloy is the most suitable substrate for application in bone implantology. [ABSTRACT FROM AUTHOR]

In this paper, we applied on the surface of the new Ti-20Nb-10Zr-5Ta alloy nano-crystalline hydroxyapatite (HA) coating by the method of the chemical deposition in a solution supersaturated with Ca2+ and [ABSTRACT FROM AUTHOR]

Background: The laparoscopic approach to a difficult splenectomy requires a longer total operative time and is frequently associated with an increased risk of bleeding and a high conversion rate. Methods: A total of 418 elective splenectomies were registered in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute between January 1995 and June 2012, of which 299 splenectomies (212 laparoscopic and 77 robotic) were performed by a single surgical team and retrospectively documented. The effect of the learning curve and the relative complexity of each type of procedure were analyzed using the Minimally Invasive Splenectomy Score, which further allowed categorizing the splenectomies as simple or difficult. Statistical analyses using the CUSUM algorithm of the intra- and postoperative parameters of the laparoscopic and robotic approaches, for both the simple and the difficult splenectomies, were performed. Results: The results of the statistical analyses clearly indicated that there was a learning curve effect for laparoscopic splenectomy but not for robotic splenectomy. When compared with the laparoscopic approach in difficult splenectomies, the robotic approach had a shorter total operative time (84.13 vs. 97.2 min), less blood loss (30.88 vs. 156.9 ml), and decreased risk of hemorrhagic complications during surgery. Conclusions: Laparoscopic splenectomy remains the approach of choice for simple splenectomies in the surgical treatment for common indications. The robotic system is particularly beneficial in difficult splenectomies (i.e., partial splenectomy, splenectomy in liver cirrhosis, splenic tumors, or malignant hemopathies). [ABSTRACT FROM AUTHOR]

An assay based on the electrochemical detection of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) for the evaluation of the total antioxidant capacity (TAC) was optimized. The assay is interchangeable with the classic spectrophotometric tests for TAC based on the same radical. In addition, it can be used for the analysis of dilute samples with low antioxidant capacities. A good linear correlation ( R2=0.97) was obtained between the results obtained with the proposed electrochemical assay and the Trolox Equivalent Antioxidant Capacity test based on ABTS radical. The assay was successfully used to evaluate the antioxidant capacity of two red wines obtained by six different maceration-fermentation techniques. [ABSTRACT FROM AUTHOR]

In this paper, we applied the potentiostatic anodisation method on the new Ti-20Nb-10Zr-5Ta alloy surface with the aim to increase its stability and bioactivity. The morphology (SEM) and composition (Raman, FT-IR) of the obtained anodisation nanolayer are studied. Also, electrochemical stability (by cyclic potentiodynamic polarisation and EIS), corrosion resistance (by linear polarisation), long-term behaviour (by monitoring of the open circuit potentials and corresponding open circuit potential gradients) and the characterisation of the layers deposited on the alloy surface after 1000 h in acid, neutral and alkaline Ringer and neutral Ringer-Brown solutions are presented. By potentiostatic anodisation, on the alloy surface was electrodeposited a continuous nanolayer containing TiO2 rutile type oxide. The anodised layer possesses better protective properties and at the same time better porosity, therefore a higher stability and bioactivity in comparison with the native passive film. After 1000 h in the testing solutions promoted the deposition of the brushite, phosphatotitanate and hydroxyapatite, precursors, respectively component of the human bone, namely this layer is bioactive. [ABSTRACT FROM AUTHOR]

A new quaternary Ti-20Nb-10Zr-5Ta alloy was thermo-mechanically processed; applying a stress of 10 ton-forces after heat treatment at 1000 °C it resulted a very homogeneous, fine microstructure characterized by the best mechanical properties: low Young's modulus (60 GPa) and high tensile strength and hardness. The corrosion behaviour of this processed alloy after long-term soaking (5000 h) in simulated human fluid (Ringer solution) was studied. SEM micrographs of as-cast and processed alloy after immersion proved that their surfaces were covered with a layer with a porous microstructure. EDX analysis detected Ca, P, and O as constituent elements of this porous layer. XPS determined the presence of the protective TiO2, Nb2O5, ZrO2, and Ta2O5 oxides and of the hydroxyapatite deposited from solution. All electrochemical parameters exhibited more favourable values for the processed alloy indicating the beneficial influence of the applied treatment. Impedance parameters revealed a nobler behaviour of the processed alloy than of the as-cast one. EIS spectra showed a passive film with two layers: a compact, inner, electronically conducting, barrier layer and an outer, porous layer. [ABSTRACT FROM AUTHOR]

A new ternary Ti-15Zr-5Nb alloy was elaborated with the aim to satisfy the most stringent requirements of a good implant material. The alloy has α + β bi-phase microstructure (by XRD and optical microscopy) and presents a proper combination between Young's modulus, elasticity and good ultimate tensile strength and 0.2% yield strength (from stress-strain tensile curve), indicating a good suitability as implant material. Electrochemical behaviour in artificial Carter-Brugirard saliva of different pH values (3.96, 7.84, and 9.11) and composition (un-doped and doped with 0.05 M NaF) that simulate the severe functional conditions in the oral cavity was evaluated. All electrochemical parameters of the new alloy revealed more favourable values than those of the CP Ti and Ti-6Al-4V ELI alloy, showing a more compact, resistant passive film formed on the new alloy surface. The corrosion rates and corresponding ion release rates for the new Ti-15Zr-5Nb alloy exhibited very low values (hundreds of times smaller) in comparison with similar commercial biomaterials. Electrochemical impedance spectra distinguished bi-layered passive film formed by inner, barrier layer and outer, porous layer. X-ray photoelectron spectra and scanning electron microscopy (SEM) observations proved that in time, protective compounds were deposited from saliva on the alloy surface, enhancing its corrosion resistance. [ABSTRACT FROM AUTHOR]

With the growing need for quality assessment of entire software systems in the industry, new issues are emerging. First, because most software quality metrics are defined at the level of individual software components, there is a need for aggregation methods to summarize the results at the system level. Second, because a software evaluation requires the use of different metrics, with possibly widely varying output ranges, there is a need to combine these results into a unified quality assessment. In this paper we derive, from our experience on real industrial cases and from the scientific literature, requirements for an aggregation method. We then present a solution through the Squale model for metric aggregation, a model specifically designed to address the needs of practitioners. We empirically validate the adequacy of Squale through experiments on ECLIPSE. Additionally, we compare the Squale model to both traditional aggregation techniques (e.g., the arithmetic mean), and to econometric inequality indices (e.g., the Gini or the Theil indices), recently applied to aggregation of software metrics. [ABSTRACT FROM AUTHOR]

Diffusion is the main mechanism to transport substances (e.g. amino-acids and proteins) within a cell. In any biological process the number of molecules is too small to satisfy the statistical assumptions implicit in diffusion theory. As an alternative, various methods to simulate diffusion have been developed, which are rather microscopic. Consequently, the time-scale and volume simulated are forcefully restricted and the final steady-state cannot be reached. In this paper we propose a macroscopic method, based on the analogy established between diffusing particles and the free electrons moving in a resistor-capacitor ( RC) circuit. The purpose of this work is to extend simulation beyond the actual limits of microscopic approaches and thus to obtain additional insight into the essential mechanism of biological systems. Analysis is performed with a publicly-released package (PSPICE). A procedure to build the electrical model and to fit its parameters is proposed. Simulation yields time-evolution of particle densities including the final steady-state and transport efficiency evaluation. Our method equally allows accounting for the presence of a crowded area in the diffusion pathway, the impact of several bursts of fabricated protein, as well as the case of transport simultaneously occurring on many directions. Several examples and a case study are provided to illustrate the effectiveness of our approach. Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society [ABSTRACT FROM AUTHOR]

We have analyzed the impact of anti-HLA antibodies present in the patients' circulation prior and/or following heart transplantation in a population of 108 pediatric recipients. Anti-HLA class I and class II antibodies were monitored by traditional CDC using donor and panel T and B lymphocytes and by SPA for detection of DSA. There was a highly significant correlation between the development of AMR and presence of CDC- or SPA-detected DSA. However, the fraction of the transplant population which remained AMR-free was much higher among patients with SPA-detected compared to CDC-detected DSA. Furthermore, long-term graft survival was negatively affected only by cytotoxic, complement-fixing anti-HLA class I antibodies developing following transplantation. Anti-HLA class I or class II antibodies detected by SPA had no effect on long-term survival rates. [ABSTRACT FROM AUTHOR]

The unfolded protein response (UPR) is an important stress signalling pathway involved in the cellular development and environmental adaptation of fungi. We investigated the importance of the UPR pathway in the pathogenicity of the plant necrotrophic fungus Alternaria brassicicola, which causes black spot disease on a wide range of Brassicaceae. We identified the AbHacA gene encoding the major UPR transcription regulator in A. brassicicola. Deletion of AbHacA prevented induction of the UPR in response to endoplasmic reticulum stress. Loss of UPR in mutants resulted in a complete loss of virulence and was also associated with a cell wall defect and a reduced capacity for secretion. In addition, our results showed that the UPR was triggered by treatment of mycelia with camalexin, i.e. the major Arabidopsis thaliana phytoalexin, and that strains lacking functional AbHacA exhibited increased in vitro susceptibility to antimicrobial plant metabolites. We hypothesize that the UPR plays a major role in fungal virulence by altering cell protection against host metabolites and by reducing the ability of the fungus to assimilate nutrients required for growth in the host environment. This study suggests that targeting the UPR pathway would be an effective plant disease control strategy. [ABSTRACT FROM AUTHOR]

The aim of the present paper was to obtain new solid forms of Norfloxacin. For this purpose Norfloxacin was recrystallized from: acetic acid and its mixtures with several organic solvents. By recrystallization of Norfloxacin from acetic acid and from its mixture with several organic solvents a new solvate was found. To evidence this new solid form of Norfloxacin different investigation techniques were used: powder X-ray diffraction, FTIR, DSC, 13C NMR spectroscopy and mass spectrometry. The solvate is consisting on Norfloxacin and acetic acid in 1:1 molar ratio and crystallizes in triclinic system and the cell parameters were determined also. [ABSTRACT FROM AUTHOR]