Synthesis, characterisation and corrosion studies of CoCrMo nanoparticles for hip implants

CoCrMo Metal on Metal (MoM) hip implants were designed to be durable, targeting a better quality of life for young, active patients. However, evidence suggests that such implants can release wear particles and metal ions due to a bio-tribocorrosion process. Metallic particles, produced by wear, at articulating interfaces of the joint surface have been linked with the formation of pseudotumors and lymphatic circulation. Whilst the ion release mechanism from the bulk alloy is the focus of many studies, it is not unreasonable to expect further corrosion of particles once they become detached from the surface of the implant. Wear debris is inherent to the process because it is an inevitable consequence of the relative motion between two opposite surfaces in contact. By this means, the removal of material due to mechanical action can generate millions of nanoparticles for each cycle of movement, which can then migrate into the tissues surrounding the implant. Several studies have indicated that metal ion levels rise after surgery and persist. Specifically metal particles spread by lymphatic circulation can continue to release ions even after removal of the source of wear. The mechanisms of ion release at this scale are still unclear along with the subsequent interaction between metal-ions and biological media (e.g. bovine serum albumin (BSA) proteins). Statistically significant toxicological studies require relatively large amounts of wear debris because most studies are based on the dose- response of triplicate assays, which could require more than a hundred milligrams of nanoparticles. However, producing large volumes of wear debris particles which match the composition, size and morphology of those generated in actual hip replacements remains extremely difficult. This study focuses on the synthesis and characterization of CoCrMo nanoparticles, which mimic metal-on-metal (MoM) wear debris from hip implants. For the synthesis process, we have used a hitherto unexplored approach employing mechanochemical milling to produce a large amount of CoCrMo mimetic wear debris over short time scales. The nanoparticles produced were found to be similar in size, shape and composition to real implant wear debris from CoCrMo hip implants. In addition, pure metals that compose the alloy were compared in terms of their electrochemical corrosion, static corrosion and protein binding. Dissolution studies indicated a much lower dissolution of cobalt than previously reported. This was attributed to the efficient separation of nanoparticles prior to solute analysis through the use of centrifugation combined with ultrafiltration. The data suggest that the previously accepted route for the release of cobalt ions may need revision. The study showed that after tribocorrosion of the CoCrMo alloy in BSA, the level of Co and Mo ions in solution increased dramatically. The increase in Mo ions could be linked with the preferential binding of Mo to the BSA proteins which results in the formation of a hard protein corona on CoCrMo and Mo particles and does not readily desorb even after washing. These findings are important as it highlighted the interaction of Mo-rich surfaces with amide groups in serum proteins and the possible formation of metal carbonyl complexes both of which can modify biological molecules, altering their ability to function properly. Electrochemical corrosion in the presence of a realistic concentration of BSA suggested that proteins play an important role in Mo dissolution from CoCrMo. Mo presumably reacts with amino acid residues present in protein molecules, initiating preferential dissolution even at low potentials, where there is no disruption of the Cr passivation layer on the CoCrMo alloy. Co and Mo samples showed active dissolution in all electrolyte solutions, whereas degradation of CoCrMo and Cr samples were controlled by a passivating oxide layer. The use of PBS accelerated the corrosion for all samples, increasing the metal ion concentration in the electrolyte and there was a high incidence and growth of pitting corrosion on Co samples. This work suggests that the role of Mo as well as Co ions should be accounted for in the tribocorrosion of CoCrMo implant alloys, particularly in terms of inflammatory and toxilogical responses

Histomorphometry and detection of glycosaminoglycans in the endocervical epithelium of pregnant rats after local administration of hyaluronidase

Objective: The aim of the study was to detect the presence of glycosaminoglycans and to investigate histomorphometric aspects of the endocervical epithelium in pregnant rats after local administration of hyaluronidase. Materials and methods: Ten pregnant rats were randomly distributed into two groups. On day 18 of pregnancy, 1mL of distilled water and 0.02 mL of hyaluronidase were administered to the control group (CG) and the study group (SG), respectively. On day 20 the rats were sacrificed, followed by dissection and removal of the uterine cervix, which was prepared for histomorphometry (endocervical epithelium thickness and leucocyte infiltration) and for immunohistochemistry with alcian blue reaction and its respective blockers. The paired Student t test was used to compare the groups. Results: The SG was characterized by reduced epithelial thickness (mean: 291.01±71.1 vs. 764.30±50.94;

Potential for hydrogen production associated to water and food in off-grid communities of Southern Africa [Resumo]

ABSTRACT: Solar energy is called to meet electricity demands for isolated, off-grid communities in Africa. However, solar electric energy is intermittent and can be stored, for a limited amount of time, in batteries, which are expensive and cause serious environmental impacts at the end of their lifetime. Conversion of the surplus electric energy to green hydrogen through water electrolysis and back to electricity, when needed, using electrolyser-fuel cells systems, is examined as a potential solution to meet the water-energy-food nexus in Southern Africa. In the framework of the Agrivoltaics concept, the main constrains, opportunities and parameters to consider its applicability are presented and discussed, in terms of its technical, economic, environmental and social impacts. In the second phase of this work the developing of a PEM electrolyser for connection to a solar PV power source and a fuel cell device, for a stand-alone application, is proposed, ensuring high reliability and energy conversion efficiencies, as well as adequate transient response and a competitive cost. It is intended as a low-carbon energy system, realising the potential for synergy in the Agrivoltaic concept, aligned with global and regional sustainability goals.N/

The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis

© 2018 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (February 2018) in accordance with the publisher’s archiving policyChronic kidney disease (CKD) is associated with an imbalanced human microbiome due not only to CKD-associated factors such as uremia, increased inflammation and immunosuppression, but also to pharmacological therapies and dietary restrictions. End-stage renal disease patients require renal replacement therapies commonly in the form of hemodialysis (HD) or peritoneal dialysis (PD). HD implies the existence of a vascular access, such as an arteriovenous fistula/graft or a venous catheter, whereas PD implies a long-term peritoneal catheter and the constant inflow of peritoneal dialysate. Also, dietary adaptations are mandatory in both therapies. This revision explores the impact of HD or PD therapies on human microbiome. HD and PD appear to be associated with different changes in the gut microbiome, for example a decrease in Proteobacteria relative abundance in HD patients and increase in PD patients. Both therapies may also have an impact on the human microbiome beyond the gut, leading to increased relative abundance of specific bacteria in the blood microbiome of HD patients and increased relative abundance of other bacteria in the peritoneal microbiome of PD patients. HD and PD catheter biofilms may also play an important role in the changes observed in these microbiomes. A more interdisciplinary approach is needed to further clarify the role of microbial groups other than bacteria in all body habitats to allow the complete understanding of the impact of HD or PD on the microbiome of CKD patients. Moreover, strategies that promote a healthy balance of the human microbiome on these patients should be explored

Agricultura irrigada em ambientes salinos.

Esta obra foi inspirada na Webinar realizada no canal da Codevasf no YouTube intitulada ?Agricultura Irrigada em Ambientes Salinos? que também dá nome ao título da publicação. A publicação está dividida em 11 capítulos. Cada palestra da Webinar foi transformada em um capítulo do livro, agregando em rede outros técnicos e temas complementares aos assuntos nela discutidos. Essa obra se constitui em uma rica coletânea de informações e pesquisas que, com certeza, contribuirá para um melhor entendimento da agricultura irrigada em ambientes salinos no Brasil e no exterior. Esperamos que este material possa ser útil para os estudantes, irrigantes e os diversos profissionais que se dedicam ao trabalho de desenvolver a agricultura irrigada de maneira sustentável em ambientes, principalmente em regiões áridas e semiáridas, onde os processos naturais e antrópicos da salinidade e sodicidade se manifestam com maior intensidade. CAPÍTULO 1 - Estratégias metodológicas para o monitoramento e espacialização da salinidade e sodicidade dos solos em projetos de irrigação. CAPÍTULO 2 – Drenagem nos projetos públicos de irrigação no semiárido brasileiro: Necessidade de drenagem nos Projetos Públicos de Irrigação no nordeste do Brasil; Estudo de caso: Projetos Públicos de Irrigação ‐ DNOCS; Estudos, pesquisas e investimentos em sistemas de drenagem; Capacidade de investimentos e alternativas ao desenvolvimento; Estudo de caso: Projetos Públicos de Irrigação da Codevasf em Petrolina – PE; Instalação de drenos subterrâneos nos projetos de irrigação; Drenagem nos projetos da Codevasf; Projeto Bebedouro; Projeto Público de Irrigação Senador Nilo Coelho; Projeto Público de Irrigação Pontal; Projeto Público de Irrigação do Sistema Itaparica. CAPÍTULO 3 - Recuperação de solos afetados por sais. CAPÍTULO 4 - Fontes de águas salobras no semiárido brasileiro: ocorrência e caracterização química. CAPÍTULO 5 - Cultivo de cana-de-açúcar em áreas salinizadas: seleção de cultivares tolerantes e manejo de irrigação. CAPÍTULO 6 - Agricultura biossalina e uso de águas salobras na produção de forragem. CAPÍTULO 7 - Estresse salino em plantas e formas de mitigação. CAPÍTULO 8 – Tratamento de águas salobras com catalisador letrolítico. CAPÍTULO 9 - Caracterização de halófitas e halotolerantes: potenciais para o uso na agricultura. CAPÍTULO 10 - Experiências com o uso de águas salobras em hidroponia no nordeste brasileiro. CAPÍTULO 11 - Uso de águas salobras com tecnologia de tratamento por catalisador eletrolítico: projetos-pilotos em comunidades rurais nos municípios de Pintadas (BA) e de Russas (CE)

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia

Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workup. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly-diagnosed AML patients. Presence of dysplasia according to MFC and WHO criteria had no prognostic value in the elderly. NGS of dysplastic cells and blasts isolated at diagnosis identified three evolutionary patterns: stable (n=12/21), branching (n=4/21) and clonal evolution (n=5/21). In patients achieving complete response, integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in approximately 80% of newly diagnosed AML patients, using techniques other than single-cell multiomics.ACKNOWLEDGEMENTS: The authors acknowledge the patients, caregivers, and the biobank of the University of Navarra. This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigacion Biom ´ edica en ´ Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/ 00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdireccion General de Investigaci ´ on Sanitaria (FIS numbers PI16/ ´ 01661, PI16/00517, and PI19/01518), and the Plan de Investigacion´ de la Universidad de Navarra (PIUNA 2014-18). This work was supported internationally by the Cancer Research UK, FCAECC, and AIRC under the Accelerator Award Program (EDITOR)

Morphological and yield responses of spineless cactus Orelha de Elefante Mexicana under different cutting intensities.

The objective was to evaluate the effects of different cutting intensities on the morphological responses and forage yield of spineless cactus Orelha de Elefante Mexicana (OEM) (Opuntia stricta (Haw.) Haw) in a 12-month cycle, receiving supplemental irrigation. Three cutting intensities were evaluated: cut preserving only the mother cladode (MOTHC), cut preserving primary cladodes (PRIMC), and cut preserving secondary cladodes (SECC), equivalent to initial residual cladode area index (rCAI) of 0.08, 0.33 and 0.69, respectively. The experiment was a randomized block design with eight replicates. The cutting intensities PRIMC and SECC resulted in higher plant height and width, total cladode number and cladode area index compared to MOTHC. The harvested plant weight, forage yield (t DM ha-1), forage accumulation rate and water use efficiency were greater for PRIMC and SECC in comparison to MOTHC. The forage yield for MOTHC was 20.92 t DM (dry matter) ha-1, while for PRIMC and SECC were 37.55 and 33.18 t DM ha-1, respectively. The final CAI was 1.23, 2.53 and 3.55 for MOTHC, SECC and PRIMC, respectively. Morphological and yield responses of OEM Spineless cactus under supplemental irrigation are influenced by cutting intensities, in which less intense cuts (preserving the primary or secondary cladodes) promote taller and wider plants, and higher forage yield

Reduced SLIT2 is Associated with Increased Cell Proliferation and Arsenic Trioxide Resistance in Acute Promyelocytic Leukemia

Simple Summary In solid tumors, the altered expression of embryonic genes such as the SLIT-ROBO family has been associated with poor prognosis, while little is known about their role in acute myeloid leukemia (AML). Previous studies reported frequent hypermethylation of SLIT2 mediated by the methyltransferase enzyme EZH2 and more recently the PML protein, which are commonly found to be aberrantly expressed in AML. Here, we aim to assess retrospectively the clinical relevance of the SLIT2 gene in acute promyelocytic leukemia, a homogenous subtype of AML. We demonstrated that reduced SLIT2 expression was associated with high leukocyte counts and reduced overall survival in different APL cohorts. STLI2 treatment decreased APL growth, while SLIT2 knockdown accelerated cell cycle progression and proliferation. Finally, reduced expression of SLIT2 in murine APL blasts resulted in fatal leukemia associated with increased leukocyte counts in vivo. These findings demonstrate that SLIT2 can be considered as a prognostic marker in APL, and a potential candidate for clinical studies of a more heterogeneous disease, such as AML. The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2(high) transcript levels were associated with cell cycle arrest, while SLIT2(low) APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92-0.97; p <0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated