Contribution of coagulation factor VII R353Q polymorphism to the risk of thrombotic disorders development (venous and arterial): A case-control study

Background: Elevated factor VII (FVII) level is a risk factor for thromboembolic disorders. It was reported that the FVII R353Q polymorphism is associated with variation in plasma FVII levels, where Q allele carriers were more associated with lower levels of FVII than R allele carriers. However, the association between coagulation FVII R353 Q polymorphisms and the risk of thrombosis is uncertain.Aim of the study: Is to investigate the contribution of factor VII R353Q gene polymorphism to the risk of thrombotic disorders development (venous and arterial) in a group of Egyptian patients.Subjects and methods: This study was conducted on 310 subjects: 110 acute myocardial infarction (AMI) patients, 108 deep venous thrombosis (DVT) patients and 92 healthy controls. FVII R353Q genotypes were assessed using restriction fragment length polymorphism analysis.Results: There were no statistically significant differences in the frequency of FVII R353Q polymorphism between each of the AMI and DVT patients and the control group (P = 0.9, 0.1). However the Q allele showed a significantly higher frequency in the AMI group (15.4%) vs. controls (8.7%) (OR: 1.92; 95% CI: 0.98–3.7). Bivariate analysis demonstrated no significant association between FVII R353Q genotypes and different studied risk factors, neither in arterial nor venous thrombosis.Conclusion: FVII R353Q polymorphism did not contribute to an increased risk of thrombosis (arterial and venous); also carrying the Q allele (of R353Q) did not confer protection against acute thrombotic events

MortaparibPlus- A Novel Anticancer Small Molecule Abrogating Mortalin-p53 Interaction in Cancer Cells

Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug. Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named MortaparibPlus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited two types of cells (different p53 status and point mutation), Colorectal Cancer Cells [HCT116 (p53WT) and DLD-1 (p53 (p53S241F)] and Luminal A Breast Cancer [MCF-7 (p53WT) and T47D (p53L194F)]. We further validated the activity of MortaparibPlus by bioinformatics/experimental analyses. Results. Through bioinformatics analysis, we discovered that MortaparibPlus has potential to block the binding site of mortalin on p53, thus, preventing the formation of mortalin-p53 complex. Immunoprecipitation analyses showed that MortaparibPlus abrogated the mortalin-p53 complex formation and caused growth arrest/apoptosis (via activation of p21WAF1, BAX, and PUMA) in HCT116, DLD-1, and MCF-7 cells. Furthermore, MortaparibPlus posed a cytotoxic effect to cancer cells through various mechanisms (inhibition of PARP1, up-regulation of p73 proteins, downregulation of mortalin and CARF proteins). In contrast, we found that, despite the hyperactivation of PARP1 (PAR accumulation and loss of ATP) as an alternative tumor suppression mechanism, MortaparibPlus-treated T47D cells exhibited signs of neither complete apoptosis nor PAR-Thanatos. Such response was associated with the failure of MortaparibPlus to inhibit the formation of AIF-mortalin complexes. Conclusions. MortaparibPlus is proposed as a potential multimodal small molecule for cancer treatment that requires further extensive laboratory and clinical studies

Experimental assessment of crack prediction methods in international design codes for edge restrained walls

Through cracking resulting from external restraint of early-age thermal and long-term shrinkage strain is a significant issue in the construction industry as it causes leakage in water retaining and resisting structures. Concerningly, a recent field study found restraint induced crack widths to frequently exceed crack widths calculated in accordance with UK design practice (BS EN 1992-3 and CIRIA C766). Due to a lack of pertinent data, the reasons for this are uncertain. This paper compares measured and predicted crack widths in a series of 12 full-scale edge restrained walls constructed in the laboratory. The tests examine the influence on cracking of key parameters including concrete mix design, wall reinforcement ratio, wall aspect ratio and relative wall to base cross-sectional area. The measured and calculated crack widths are compared at first cracking and at the end of monitoring. Two types of behaviour were noted in the tests, dependent on when the first cracks formed. Cracking either occurred at early age, within 24 h of stripping the formwork, or later due to restraint of combined early age thermal contraction and shrinkage. The final crack widths were greatest, by a considerable margin, in walls where cracks formed at early age, despite the initial cracks being very narrow. BS EN 1992-3 gives the best estimates of crack width in the two walls that cracked at early age. Crack widths in these walls were significantly underestimated by C766. In the other 10 walls, which cracked later, C766 tends to give the best estimate of crack width

Rheumatic tricuspid valve disease: Repair versus Replacement

Background: Tricuspid valve disease is most commonly functional, however, organic affection still accounts for one fourth of cases. Rheumatic fever which is endemic in Egypt is a main cause of organic affection. Current practice largely relies on tricuspid valve repair; however, it has been difficult to determine optimal procedure. Objectives: Herein, we study the outcome of replacement versus repair in such patients. Patients and methods: A prospective study was conducted on 300 consecutive patients with rheumatic heart disease showing severe tricuspid valve affection underwent tricuspid valve surgery, between 2014 and 2018. The patients were divided into two groups; TVR group (n=150) which included patients who underwent tricuspid valve replacement and TVr group (n=150) which included patients who underwent tricuspid valve repair. Diagnosis and follow up were done by echocardiography. Peri-operative variables, clinical outcome, morbidity, mortality, and follow up data were recorded. Results: Mean follow-up was 4±1.32 years. In-hospital mortality was 6 patients (4%) in TVR group and 3 patients (2%) in TVr group (P value ≥ 0.05). Postoperative low cardiac output syndrome and stroke were significantly higher in the repair group. Postoperative RV dysfunction, renal impairment, renal failure and chest re-exploration were significantly higher in the replacement group. Severe tricuspid regurgitation was reported in 19 patients (12.6%) of the repair group on follow up. Conclusion: Tricuspid valve repair is preferable to replacement to avoid the drawbacks of prosthesis. However, tricuspid valve replacement is feasible with comparable survival outcome and the progressive nature of the rheumatic disease may recommend replacement

Semantic segmentation of microbial alterations based on SegFormer

IntroductionPrecise semantic segmentation of microbial alterations is paramount for their evaluation and treatment. This study focuses on harnessing the SegFormer segmentation model for precise semantic segmentation of strawberry diseases, aiming to improve disease detection accuracy under natural acquisition conditions.MethodsThree distinct Mix Transformer encoders - MiT-B0, MiT-B3, and MiT-B5 - were thoroughly analyzed to enhance disease detection, targeting diseases such as Angular leaf spot, Anthracnose rot, Blossom blight, Gray mold, Leaf spot, Powdery mildew on fruit, and Powdery mildew on leaves. The dataset consisted of 2,450 raw images, expanded to 4,574 augmented images. The Segment Anything Model integrated into the Roboflow annotation tool facilitated efficient annotation and dataset preparation.ResultsThe results reveal that MiT-B0 demonstrates balanced but slightly overfitting behavior, MiT-B3 adapts rapidly with consistent training and validation performance, and MiT-B5 offers efficient learning with occasional fluctuations, providing robust performance. MiT-B3 and MiT-B5 consistently outperformed MiT-B0 across disease types, with MiT-B5 achieving the most precise segmentation in general.DiscussionThe findings provide key insights for researchers to select the most suitable encoder for disease detection applications, propelling the field forward for further investigation. The success in strawberry disease analysis suggests potential for extending this approach to other crops and diseases, paving the way for future research and interdisciplinary collaboration

Functionalization of polyacrylonitrile/Na-Y-zeolite composite with amidoxime groups for the sorption of Cu(II), Cd(II) and Pb(II) metal ions

International audienceA composite material (PAN-Na-Y-zeolite) was prepared by polymerization of acrylonitrile in the presence of Na-Y zeolite. The A composite was functionalized by amidoximation through the reaction of hydroxylamine on nitrile groups of the composite. The sorbent (APNa-Y-zeolite) was fully characterized by FTIR spectrometry, XRD diffraction, thermogravimetric analysis, scanning electron microscopy, zetametry and BET analysis. The sorption properties of APNa-Y-zeolite were investigated for the recovery of Cu(II), Cd(II) and Pb(II) from synthetic solutions before being tested for the purification of local tap water. Sorption properties were characterized through the study of pH effect, uptake kinetics, sorption isotherms. The pseudo-second order rate equation fitted well kinetic profiles. Sorption isotherms were modeled using the Langmuir, the Freundlich and the Sips equations. Thermodynamic parameters were evaluated through variation of temperature. While the sorption of Cu(II) and Cd(II) was endothermic, Pb(II) recovery was exothermic. Metal ions were successfully desorbed using 5 M HCl solutions. High concentrations of NaCl hardly alter sorption performance, contrary to humic acid that slightly reduces metal binding

Assessment of cracking performance in edge restrained RC walls

Excessive cracking due to restraint of thermal and shrinkage strains is a widespread problem in the concrete construction industry. In design, restraint induced cracking is managed by the provision of reinforcement intended to distribute internal strains in such a way as to control the cracking pattern and limit crack widths. The area of secondary (horizontal) reinforcement required in members such as retaining walls and water tanks is often governed by the need to control early age thermal cracking. This paper presents results from four edge restrained walls tested at Imperial College London and the University of Leeds as part of an Engineering and Physical Sciences Research Council funded project into restraint induced cracking. The paper describes the development of volumetric strain and cracking in the tested walls. The cracking performance is assessed by comparing the restrained strain with the tensile strain capacity of concrete