Rationale for Medium Cutoff Membranes in COVID-19 Patients Requiring Renal Replacement Therapy

The current pandemic of coronavirus disease 2019 (COVID-19) spotlighted the vulnerability of patients with chronic kidney disease stage 5 on maintenance hemodialysis (HD) to the viral infection. Social distancing is the most effective preventive measure to reduce the risk of infection. Nonetheless, the necessity to frequently reach the dialysis center and the inherent social gathering both impede social distancing and also self-quarantine for infected individuals. A baseline hyperinflammatory state driven by factors such as the retention of uremic toxins afflicts these patients. Concomitantly, a condition of relative immunosuppression is also attributed to similar factors. The use of high-flux (HF) dialyzers for HD is the standard of care. However, with HF membranes, the removal of large middle molecules is scant. Medium cutoff (MCO) dialyzers are a new class of membranes that allow substantial removal of large middle molecules with negligible albumin losses. Recent trials confirmed long-term safety and long-term sustained reduction in the concentration of large uremic toxins with MCO dialyzers. Herein, we discuss the rationale for applying MCO membranes in COVID-19 patients and its possible immunoadjuvant effects that could mitigate the burden of COVID-19 infection in dialysis patients. We also discuss the direct cytopathic effect of the virus on renal tissue and extracorporeal blood purification techniques that can prevent kidney damage or reduce acute kidney injury progression

Base de dados climáticos.

Um repositório organizado de dados é uma exigência em qualquer empresa, como componente de eficiência, e a forma adequada para isto é utilizar uma ferramenta de banco de dados. Focando a pesquisa agropecuária, que necessita de dados climáticos como um dos componentes do ambiente que condicionam a produção, ter esses dados atualizados e disponíveis para acesso é uma necessidade para a empresa. A primeira ferramenta de banco de dados surgiu na IBM como forma de reduzir trabalho e custo no armazenamento e organização de dados, e o modelo relacional de banco de dados, utilizado neste documento, surgiu na década de 70, e até hoje é um dos mais utilizados, com a Linguagem Estruturada de Consulta – SQL, desenvolvida na década de 80, e adotada universalmente. Desta forma, o produto apresentado nesta publicação é uma forma de permitir o acesso aos usuários a toda base climática disponível na Unidade até 2011, ao mesmo tempo popularizando um sistema de banco de dados para o grupamento de pesquisa, por meio de um passo a passo.bitstream/item/70054/1/doc-141.pd

Cinacalcet adherence in dialysis patients with secondary hyperparathyroidism in Lombardy Region: clinical implications and costs

Background: Patients on dialysis often have secondary hyperparathyroidism (SHPT), a disorder associated with renal osteodystrophy, progressive vascular calcification, cardiovascular disease, and death. The objective of this retrospective observational study was to evaluate, in dialysis patients with SHPT, the impact of different levels of adherence to cinacalcet therapy on hospitalisations and direct healthcare costs charged to the Lombardy Regional Health Service (Italy). Methods: Data recorded in the administrative databases on all citizens undergoing dialysis between 1 January 2011 and 31 December 2011 were selected. For the aim of this study, patients with SHPT already on dialysis in the first 6 months of 2009 who had been treated with cinacalcet for at least 365 days were selected and retrospectively analysed through to end of 2012. Healthcare resource utilisation, cinacalcet adherence, and costs for medication, hospitalisations, and diagnostic/therapeutic procedures were estimated. Results: A total of 994 patients were identified (mean age 63.0 years, females 43.5%). The first patient tertile had an adherence to cinacalcet of <64.1%, whereas the third had an adherence of over 91.5%. Patients in the third adherence tertile experienced fewer all-causes hospitalisations than those in the first tertile (-19.2%; p=0.01423), fractures (-37.1%; p=0.59422), cardiovascular disease (-23.8%; p=0.04025), and sepsis (-32.3%; p=0.01386). The increase in costs for cinacalcet-adherent patients is almost completely offset by the reduction in costs for hospitalisations. Conclusions: The results of the analysis suggest that there may be some correlation between a high level of cinacalcet adherence and a decrease in hospitalisations

Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion

SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pathway as causal to differentiation

Background: Despite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation.Results: We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the most of membrane proteins found to be modulated are involved in cell-to-cell signaling/interaction pathways. Moreover, the upstream prediction analysis of proteins involved in cell-to-cell signaling and interaction unveiled that the activation of the mesenchymal to epithelial transition (MET), by the repression of TGFB1/Slug signaling, may be causal to hepatocyte differentiation.Conclusions: Taken together, this study increases the understanding of the underlying mechanisms modulating the complex biological processes of hepatic stem cell proliferation and differentiation. © 2014 Montaldo et al.; licensee BioMed Central Ltd

Experimental and computational studies on the formation of cyanate from early metal terminal nitrido ligands and carbon monoxide

An important challenge in the artificial fixation of N[subscript 2] is to find atom efficient transformations that yield value-added products. Here we explore the coordination complex mediated conversion of ubiquitous species, CO and N[subscript 2], into isocyanate. We have conceptually split the process into three steps: (1) the six-electron splitting of dinitrogen into terminal metal nitrido ligands, (2) the reduction of the complex by two electrons with CO to form an isocyanate linkage, and (3) the one electron reduction of the metal isocyanate complex to regenerate the starting metal complex and release the product. These steps are explored separately in an attempt to understand the limitations of each step and what is required of a coordination complex in order to facilitate a catalytic cycle. The possibility of this cyanate cycle was explored with both Mo and V complexes which have previously been shown to perform select steps in the sequence. Experimental results demonstrate the feasibility of some of the steps and DFT calculations suggest that, although the reduction of the terminal metal nitride complex by carbon monoxide should be thermodynamically favorable, there is a large kinetic barrier associated with the change in spin state which can be avoided in the case of the V complexes by an initial binding of the CO to the metal center followed by rearrangement. This mandates certain minimal design principles for the metal complex: the metal center should be sterically accessible for CO binding and the ligands should not readily succumb to CO insertion reactions.National Science Foundation (U.S.) (CHE-1111357

Yield performance and physiological response of a maize early hybrid grown in tunnel and open air under different water regimes

Climate change is one of the most important and studied phenomena of our age and it can have a deep impact on agriculture. Mediterranean countries are and will continue to be strongly affected by changing environmental factors, including lack of precipitation and prolonged heatwaves. The current study aimed to assess the adaptability of an early maize hybrid grown in two temperature conditions and subjected to different irrigation water regimes. The experimen-tal design was a randomized complete-block design with two different temperature conditions: (i) ordinary temperature in open field (OF) and (ii) high temperature (about 3◦ C higher than the current condition) under a poly-ethylene tunnel (PE). In both environments, five irrigation level treatments were applied: 100% (DI100), 75% (DI75), 50% (DI50), 25% (DI25), and 0% restoration of water lost by evapotranspiration (DI0). The responses of maize plants were assessed in terms of yield, nitrogen content determination, nitrogen use efficiency, leaf gas exchanges, and leaf water potential measurements. In both conditions, yield and its components linearly decreased as the irrigation water amount reduced, and even the DI0 plants did not produce. Notably, the PE-DI100 treatment had a significantly higher yield than the corresponding treatment in the open air (9.9 vs. 8.5 t ha−1 ), due mainly to the increased number of ears per square meter (13 vs. 11 m2, respectively). Though, as far as it concerns physiological parameters, a significant effect of environmental conditions was found, with values significantly lower under the protected environment, compared to the plants in the open field. Considering our results, it can be assumed that correct management of amount and time intervals of irrigation could adapt the maize to future climate change

Variability in Floral Scent in Rewarding and Deceptive Orchids: The Signature of Pollinator-imposed Selection?

Background and Aims A comparative investigation was made of floral scent variation in the closely related, food-rewarding Anacamptis coriophora and the food-deceptive Anacamptis morio in order to identify patterns of variability of odour compounds in the two species and their role in pollinator attraction/avoidance learning. Methods Scent was collected from plants in natural populations and samples were analysed via quantitative gas chromatography and mass spectrometry. Combined gas chromatography and electroantennographic detection was used to identify compounds that are detected by the pollinators. Experimental reduction of scent variability was performed in the field with plots of A. morio plants supplemented with a uniform amount of anisaldehyde. Key Results Both orchid species emitted complex odour bouquets. In A. coriophora the two main benzenoid compounds, hydroquinone dimethyl ether (1,4-dimethoxybenzene) and anisaldehyde (methoxybenzaldehyde), triggered electrophysiological responses in olfactory neurons of honey-bee and bumble-bee workers. The scent of A. morio, however, was too weak to elicit any electrophysiological responses. The overall variation in scent was significantly lower in the rewarding A. coriophora than in the deceptive A. morio, suggesting pollinator avoidance-learning selecting for high variation in the deceptive species. A. morio flowers supplemented with non-variable scent in plot experiments, however, did not show significantly reduced pollination success. Conclusions Whereas in the rewarding A. coriophora stabilizing selection imposed by floral constancy of the pollinators may reduce scent variability, in the deceptive A. morio the emitted scent seems to be too weak to be detected by pollinators and thus its high variability may result from relaxed selection on this floral trai

Mechanical behavior of biopolymer composite coatings on plastic films by depth-sensing indentation : a nanoscale study

Fundamental physical behaviors of materials at the nanoscale level are crucial when local aspects govern the macroscale performance of nanocomposites, e.g., interface and surface phenomena. Because of the increasing interest in biopolymer nanocomposite coatings for many different applications (e.g., optical devices, displays/screens, and packaging), this work investigates the potential of nanoindentation as a method for clarifying the interplay between distinct phases (i.e., organic and inorganic) at local level in thin biopolymer films loaded with nanoparticles. The nanomechanical features of pullulan nanocomposite coatings laid on polyethylene terephthalate (PET) were quantified in terms of elastic modulus (E), hardness (H), and creep (C) through an instrumented indentation test composed of a loading-holding-unloading cycle. Colloidal silica (CS) and cellulose nanocrystals (CNCs) were used as spherical and rod-like nanoparticles, respectively. An overall reinforcing effect was shown for all nanocomposite coatings over the pristine (unfilled) pullulan coating. A size effect was also disclosed for the CS-loaded surfaces, with the highest E value recorded for the largest particles (8.19\u202f\ub1\u202f0.35\u202fGPa) and the highest H value belonging to the smallest ones (395.41\u202f\ub1\u202f25.22\u202fMPa). Comparing CS and CNCs, the addition of spherical nanoparticles had a greater effect on the surface hardness than cellulose nanowhiskers (353.50\u202f\ub1\u202f83.52\u202fMPa and 321.36\u202f\ub1\u202f43.26\u202fMPa, respectively). As for the elastic modulus, the addition of CS did not provide any improvement over both the bare and CNC-loaded pullulan coatings, whereas the coating including CNCs exhibited higher E values (p\u202f<\u202f.05). Finally, CS-loaded pullulan coatings were the best performing in terms of C properties, with an average indentation depth of 16.5\u202f\ub1\u202f1.85\u202fnm under a load of 3c190\u202f\u3bcN. These results are discussed in terms of local distribution gradients, surface chemistry of nanoparticles, and how nanoparticle aggregation occurred in the dry nanocomposite coatings