Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma.Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma

A Preliminary Investigation of Smart Rural Water Distribution Systems in the Gambia

This is the final version. Available on open access from Scientific Research Publishing via the DOI in this recordAn estimated one-third of water points in rural sub-Saharan Africa are non-functioning at any one time because of lack of upkeep. Communities are left without access to clean drinking water and this has multiple knock-on developmental impacts. An innovative pre-payment and Internet-of-Things enabled “e-Tap” based water technology and management system cycles revenue back into operation and maintenance and collects accurate and real-time data on consumption and tap failures. This has been operational in the Gambia since April 2016. Preliminary research has begun on evaluating this innovation. Technical tests were conducted to examine the efficiency of the e-Tap under varying conditions. Water use trends were then analysed by using the cloud-collected data transmitted from operational e-Taps. Further, baseline surveys to investigate social parameters were undertaken on 20 user households. This exploratory research shows the e-Taps to work efficiently in the laboratory and the Gambia with negligible failures, and to reduce distances users must travel for clean water and time they spend collecting

Folliculogenesis and follicular fluid adiponectin in cows: Its alterations and relationships with ovarian function [Folikulogeneza i adiponektin u folikularnoj tekućini krava: Promjene i odnos s funkcijom jajnika]

The objectives of the present study were to study the dynamic changes in adiponectin concentration in the growing luteal as well as the preovulatory follicles in dairy cows. In the first study, the ovaries and blood of 15 Holstein dairy cows in the luteal phase were collected from a slaughterhouse. Clear antral follicles were divided into three diameter groups (small, 3-5 mm; medium, 6-9 mm and large, ≥10 mm) and their fluid was aspirated. In the second study, the coccygeal blood and fluid of the preovulatory follicles of eight live Holstein dairy cows were aspirated transrectally, using a transrectal-guided fine-needle. Concentrations of adiponectin in the serum, and follicular fluid and progesterone in the serum were measured. Serum adiponectin concentrations in both luteal and follicular phases were higher than the follicular fluid adiponectin concentrations in all types of follicles (P0.05), and the reduction was seen in preovulatory follicles in comparison with small follicles (P = 0.001). In the luteal phase, a significant positive correlation was observed between the adiponectin concentrations in different sized follicles, and also in the serum progesterone and follicular fluid adiponectin of follicles (P<0.05). In conclusion, lower adiponectin concentrations in blood serum and preovulatory follicles in comparison to luteal growing follicles reflect the effect of ovarian stage on adiponectin alterations

Aspects of computational homogenization at finite deformations: A unifying review from Reuss' to Voigt's Bound

The objective of this contribution is to present a unifying review on strain-driven computational homogenization at finite strains, thereby elaborating on computational aspects of the finite element method. The underlying assumption of computational homogenization is separation of length scales, and hence, computing the material response at the macroscopic scale from averaging the microscopic behavior. In doing so, the energetic equivalence between the two scales, the Hill Mandel condition, is guaranteed via imposing proper boundary conditions such as linear displacement, periodic displacement and antiperiodic traction, and constant traction boundary conditions. Focus is given on the finite element implementation of these boundary conditions and their influence on the overall response of the material. Computational frameworks for all canonical boundary conditions are briefly formulated in order to demonstrate similarities and differences among the various boundary conditions. Furthermore, we detail on the computational aspects of the classical Reuss' and Voigt's bounds and their extensions to finite strains. A concise and clear formulation for computing the macroscopic tangent necessary for FE2 calculations is presented. The performances of the proposed schemes are illustrated via a series of two- and three-dimensional numerical examples. The numerical examples provide enough details to serve as benchmarks. © 2016 by ASME

Pancreatic Allograft Thrombosis: Suggestion for a CT grading system and management algorithm

Pancreatic allograft thrombosis (PAT) remains the leading cause of non-immunological graft failure. Herein we propose a new CT grading system of PAT to identify risk factors for allograft loss and outline a management algorithm by retrospective review of consecutive pancreatic transplants between 2009-2014. Triple-phase CT scans were graded independently by two radiologists as; Grade 0 – no thrombosis, Grade 1 – peripheral thrombosis, Grade 2 – intermediate non-occlusive thrombosis and Grade 3 – central occlusive thrombosis. Twenty-four of 103 (23.3%) recipients were diagnosed with PAT (including grade 1). Three grafts (2.9%) were lost due to portal vein thrombosis. On multivariate analysis, pancreas after SPK/PAK transplant, acute rejection and CT finding peri-pancreatic oedema and/or inflammatory change were significant risk factors of PAT. Retrospective review of CT images revealed more grade 1 and 2 thromboses than were initially reported. There was no significant difference in graft or patient survival, post-operative stay or morbidity of recipients with grade 1 or 2 thrombosis who were or were not anticoagulated. Our data suggest that therapeutic anticoagulation is not necessary for grade 1 and 2 arterial and grade 1 venous thrombosis. The proposed grading system can assist clinicians in decision making and provide standardised reporting for future studies

Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine.

BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5-3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer's solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5-3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions

Evaluating environmental effects in construction and demolition waste recycling plant with the Iranian Leopold Matrix method

BACKGROUND AND OBJECTIVES: Recycling and reusing construction and demolition debris is a productive step toward solving this problem. Still, the recycling process also leaves industrial effluents, which is evident in producing recycled sand. The present research has investigated the environmental effects of recycling construction debris at sand recycling plants. Considering the negative impacts of sand washing mud produced at the plant in the Aab'Ali Landfill of Tehran in Iran, the material's physicochemical characteristics and environmental impact have also been investigated to regulate practices.                        METHODS: The Environmental Impact Assessment has been carried out in physicochemical, biological, socio-cultural, and economic-technical areas. Due to the large dispersion of the studied soil and the composition diversity in each sampling, 30 samples of the sand washing mud and the material mixed with the surrounding soil have been collected. The exploitation phase during the factory construction plan's implementation stage was considered the current research's main phase. Hence, 13 micro activities and 23 environmental parameters were identified, and the results were analyzed in the Environmental Impact Assessment Plus Software using the Iranian Leopold Matrix method and discussed based on the results of the experiments.FINDINGS: According to the results of the matrix calculation, the three micro-activities included washing the sand through a sand-washing machine, fine sand washing through the EvoWash machine with a score of -3.6, converting concrete pieces and large boulders into smaller pieces by jackhammers, transferring to the jaw crusher machine with a score of -2.8, and transferring the remaining sand washing mud produced by the EvoWash machine to the storage pond with a score of -2.7 had the most negative effects. The three micro-activities of waste processing for green space irrigation (+2.2), selling products (+0.9), and hiring employees with a score of +0.5 have the most positive effects on the environment. As ranking smaller than -31 forming 50% of the total average of rows and columns, the activity of the plant and the sand extraction process in this landfill is approved by providing modification alternatives.CONCLUSION: Considering the positive impact on the economy, increasing green spaces in the region, job creation, and also reducing the amount of increasing debris accumulated in the landfill is evaluated positively and can be done considering the reforms; including the prevention of releasing remnant sand washing mud freely and recycling it instead. Reusing the sand washing mud requires improving the water purification systems used in the EvoWash machine

Production of Silver Nanoparticles with Strong and Stable Antimicrobial Activity against Highly Pathogenic and Multidrug Resistant Bacteria

Aims. To synthesize, characterize, and analyze antimicrobial activity of AgNPs of Escherichia hermannii (SHE), Citrobacter sedlakii (S11P), and Pseudomonas putida (S5). Methods. The synthesized AgNPs were examined using ultraviolet-visible spectroscopy (UV-vis) and, zeta potential, and the size and the morphology obtained from the three different isolates were also confirmed by TEM. Results. Among the three isolates tested, SHE showed the best antimicrobial activity due to the presence of small (4–12 nm) and stable (−22 mV) AgNPs. Stability of AgNPs was also investigated and found to be dependent on the nature of isolates. Conclusion. Produced AgNPs showed particle stability and antimicrobial efficacy up to 90 days of production. Our AgNPs exhibited greater antimicrobial activity compared with gentamicin against P. aeruginosa isolates and vancomycin against S. aureus and MRSA isolates at very low concentration (0.0002 mg per Microliters)

Digital Avatars for Older People’s Care

Es el preprint de: Bertoa M.F., Moreno N., Perez-Vereda A., Bandera D., Álvarez-Palomo J.M., Canal C. (2020) Digital Avatars for Older People’s Care. In: García-Alonso J., Fonseca C. (eds) Gerontechnology. IWoG 2019. Communications in Computer and Information Science, vol 1185. Springer, Cham. doi:10.1007/978-3-030-41494-8_6.The continuous increase in life expectancy poses a challenge for health systems in modern societies, especially with respect to older people living in rural low-populated areas, both in terms of isolation and difficulty to access and communicate with health services. In this paper, we address these issues by applying the Digital Avatars framework to Gerontechnology. Building on our previous work on mobile and social computing, in particular the People as a Service model, Digital Avatars make intensive use of the capabilities of current smartphones to collect information about their owners, and applies techniques of Complex Event Processing extended with uncertainty for inferring the habits and preferences of the user of the phone and building with them a virtual profile. These virtual profiles allow to monitor the well-being and quality of life of older adults, reminding pharmacological treatments and home health testings, and raising alerts when an anomalous situation is detected.This work has been funded by the Spanish Government under grant PGC2018-094905-B-100