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

The intriguing case of motor neuron disease: ALS and SMA come closer

MNDs (motor neuron diseases) form a heterogeneous group of pathologies characterized by the progressive degeneration of motor neurons. More and more genetic factors associated with MND encode proteins that have a function in RNA metabolism, suggesting that disturbed RNA metabolism could be a common underlying problem in several, perhaps all, forms of MND. In the present paper we review recent developments showing a functional link between SMN (survival of motor neuron), the causative factor of SMA (spinal muscular atrophy), and FUS (fused in sarcoma), a genetic factor in ALS (amyotrophic lateral sclerosis). SMN is long known to have a crucial role in the biogenesis and localization of the spliceosomal snRNPs (small nuclear ribonucleoproteins), which are essential assembly modules of the splicing machinery. Now we know that FUS interacts with SMN and pathogenic FUS mutations have a significant effect on snRNP localization. Together with other recently published evidence, this finding potentially links ALS pathogenesis to disturbances in the splicing machinery, and implies that pre-mRNA splicing may be the common weak point in MND, although other steps in mRNA metabolism could also play a role. Certainly, further comparison of the RNA metabolism in different MND will greatly help our understanding of the molecular causes of these devastating diseases

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

Lysines Acetylome and Methylome Profiling of H3 and H4 Histones in Trichostatin A-Treated Stem Cells

Trichostatin A ([R-(E,E)]-7-[4-(dimethylamino) phenyl]-N-hydroxy- 4,6-dimethyl- 7-oxo-2,4-heptadienamide, TSA) affects chromatin state through its potent histone deacetylase inhibitory activity. Interfering with the removal of acetyl groups from lysine residues in histones is one of many epigenetic regulatory processes that control gene expression. Histone deacetylase inhibition drives cells toward the differentiation stage, favoring the activation of specific genes. In this paper, we investigated the effects of TSA on H3 and H4 lysine acetylome and methylome profiling in mice embryonic stem cells (ES14), treated with trichostatin A (TSA) by using a new, untargeted approach, consisting of trypsin-limited proteolysis experiments coupled with MALDI-MS and LC-MS/MS analyses. The method was firstly set up on standard chicken core histones to probe the optimized conditions in terms of enzyme:substrate (E:S) ratio and time of proteolysis and, then, applied to investigate the global variations of the acetylation and methylation state of lysine residues of H3 and H4 histone in the embryonic stem cells (ES14) stimulated by TSA and addressed to differentiation. The proposed strategy was found in its simplicity to be extremely effective in achieving the identification and relative quantification of some of the most significant epigenetic modifications, such as acetylation and lysine methylation. Therefore, we believe that it can be used with equal success in wider studies concerning the characterization of all epigenetic modifications

Health-related quality of life burden in scleroderma patients treated with two different intravenous iloprost regimens

Systemic sclerosis (SSc)-related Raynaud's phenomenon (RP) and digital ulcers (DU) can impair health-related quality of life (HRQoL). The aim of our study was to estimate HRQoL in SSc patients treated with two different intravenous (IV) iloprost (ILO) regimens and in patients not treated with IV ILO. 96 consecutive SSc patients were enrolled in a pragmatic, prospective and non-randomized study, and divided into 3 groups: not requiring therapy with IV ILO (N=52), IV ILO once monthly (N=24) or IV ILO for 5 consecutive days every 3 months (N=20). Patients were followed up for three months. We assessed HRQoL using the generic preference-based questionnaire EQ-5D-5L. We conducted multiple regression analyses to estimate, in each treatment group, the mean general health (GH) and the mean utility index of the EQ-5D-5L, adjusting for possible confounders. The mean adjusted utility index and GH score, after three months' follow-up, were not different in the three groups: IV ILO was able to make patients requiring IV ILO similar to those not requiring it. Moreover, there was no difference in this model between the two ILO regimens (1 day monthly vs 5 consecutive days every 3 months). The two different IV ILO regimens (the most appropriate regimen was decided according to patients' characteristics and needs) were able to stabilize HRQoL in RP secondary to SSc non-adequately controlled by oral therapy

Self-related consequences of death fear and death denial

This study explores self-related outcomes (e.g., esteem, self-concept clarity, existential well-being) as a function of the interaction between self-reported levels of death fear and death denial. Consistent with the idea that positive existential growth can come from individuals facing, rather than denying, their mortality (Cozzolino, 2006), the authors observed that not fearing and denying death can bolster important positive components of the self. That is, individuals low in death denial and death fear evidenced an enhanced self that is valued, clearly conceived, efficacious, and that has meaning and purpose

Phosphorus species in sequentially extracted soil organic matter fractions

The majority of organic P (Porg) in soil is considered to be part of soil organic matter (SOM) associations, but its chemical nature is largely ‘unresolved’. In this study, we investigated the Porg composition in different SOM fractions of a Gleysol soil using the Humeomics sequential chemical fractionation (SCF) procedure combined with nuclear magnetic resonance (NMR) spectroscopy. In summary, SCF procedure with subsequent NaOH-EDTA extraction of the soil residue extracted a total of 1769 mg P/kgsoil compared to 1682 mg P/kgsoil of a single-step NaOH-EDTA extraction. Approximately 38 % of the extracted Porg was present in the form of the unresolved Porg pool, which was represented by one or two underlying broad signals in the phosphomonoester region of solution 31P NMR spectra. The SCF revealed that phosphomonoesters were recovered in each fraction: 47 % of the unresolved phosphomonoesters were associated with the SOM fraction released by breaking ester bonds (40 %) and ether bonds (7 %), whereas about 30 % of this unresolved Porg pool appeared in the SOM fraction closely associated with the soil mineral phase. Furthermore, the extractability of inositol phosphates (IP) was increased from 312 mg P/kgsoil to 534 mg P/kgsoil (factor 1.7) using the SCF procedure compared to a single-step NaOH-EDTA extraction. Previous studies have reported the presence of IP in molecular size fractions greater than 10 kDa. Our findings on the removal of IP with the fractionation of the SOM could explain the presence of IP in these large associations. We demonstrate that major pools of Porg are closely associated with SOM structures, comprising a diverse array of chemical species and bonding types. These results forward our understanding of Porg stabilisation, P transformation, and P cycling in terrestrial ecosystems towards an association point of view

Diagnosing and Treating Food Allergy

t Food allergy (FA) is defined as an abnormal immunological reaction to food proteins. Over 90 % of FAs in childhood are caused by eight foods: cow’s milk, hen’s egg, soy, peanuts, tree nuts, wheat, fish and shellfish. The diagnostic work up for a child with suspected FA includes detailed medical history, physical examination, FA screening tests and response to elimination diet and to oral food challenge. Sometimes additional diagnostic tools to explore intestinal damage and function could be adopted. Currently, the only treatment for FA relies on strict elimination diets supervised by the nutritionist. Main new therapeutic strategies for FA include allergen-specific (oral, sublingual, epicutaneous, subcutaneous immunotherapy and heat treatment of food) and nonallergen-specific therapies (humanized monoclonal antibodies, anti-IgE and anti-IL5, probiotics). An incorrect diagnosis is likely to result in unnecessary dietary restrictions, which, if prolonged, may adversely affect the child’s nutritional status and growt