Reproducible,biocompatible medical materials from biologically derived polysaccharides: Processing and Characterization

Natural polysaccharides like chitosan and dextran have garnered considerable interest in biomedical applications due to their biocompatibility, biodegradability, and nontoxicity. Nonetheless, the development of a reproducible class of medical devices from these materials is challenging and has had limited success. Chitosan and dextran are inherently variable and synthesis using these materials is prone to inconsistencies. In this study, we put forward a robust product development regimen that allows these natural materials to be developed into a reproducible class of biomaterials. First, an array of validated characterization methods (Proton Nuclear Magnetic Resonance, titrations, Ultraviolet spectroscopy, Size Exclusion Chromatography—Multi-Angle Light Scattering, Size Exclusion Chromatography—Refractive Index, and proprietary methods) were developed that allowed rigorous specifications to be set for unprocessed chitosan and dextran, chitosan and dextran intermediates, and chemically modified materials—acrylated chitosan (aCHN) and oxidized dextran (oDEX). Second, a robust and reproducible synthesis scheme involving various in-process controls was developed to chemically modify the unprocessed polysaccharides. Third, purification methods to remove byproducts and low-molecular-weight impurities for both aCHN and oDEX were developed. The study presents a viable strategy for converting variable, natural materials into a reproducible class of biomaterials that can be applied in various biomedical applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48454.     

3D printed millireactors for process intensification

The scope of the present research aims at demonstrating the 3D printing use in the manufacturing of microchannels for chemical process applications. A comparison among digital model processing applications for 3D print(slicers) and a print layer thickness analysis were performed. The 3D print fidelity was verified in several devices, including the microchannels' printing with and without micromixer zones. In order to highlight the 3D print potential in Chemical Engineering, the biodiesel synthesis was also carried out in a millireactor manufactured by 3D printing. The millireactor operated under laminar flow regime with a total flow rate of 75.25 ml ? min~(-1)(increment of about 130 times over traditional microdevices used for biodiesel production).The printed millireactor provided a maximum yield of Ethyl Esters of 73.51% at 40 °C, ethanol:oil molar ratio of7 and catalyst concentration of 1.25 wt% and residence time about 10 s. As a result of flow rate increment attained in the millireactor, the number of required units for scaling-up the chemical processes is reduced. Using the approach described in the present research, anyone could produce their own millireactor for chemical process in a simple way with the aid of a 3D printer.     

Carbon footprint as an instrument for enhancing food quality: overview of the wine,olive oil and cereals sectors

The quantification of greenhouse gases (GHG) emissions represents a critical issue for the future development of agro‐food produces. Consumers' behaviour could play an important role in requiring environmental performance as an essential element for food quality. Nowadays, the carbon footprint (CFP) is a tool used worldwide by agro‐food industries to communicate environmental information. This paper aims to investigate the role that CFP could have in consumers' choices in three significant agro‐food sectors in the Mediterranean area: wine, olive oil and cereals. A critical review about the use of CFP was carried out along the supply chain of these three sectors, in order to identify opportunities for enhancing food quality and environmental sustainability and highlighting how environmental information could influence consumers' preferences. The analysis of the state of the art shows a great variability of the results about GHG emissions referred to agricultural and industrial processes. In many cases, the main environmental criticisms are linked to the agricultural phase, but the other phases of the supply chain could also contribute to the increased CFP. However, despite the wide use of CFP by companies as a communication tool to help consumers' choices in agro‐food products, some improvements are needed in order to provide clearer and more understandable information. © 2016 Society of Chemical Industry     

Four-year longitudinal study of conduct disorder in boys: Patterns and predictors of persistence.

A prospective study of conduct disorder (CD) was conducted using 4 annual structured diagnostic interviews of 171 clinic-referred boys, their parents, and their teachers. Only about half of the 65 boys who met criteria for CD in Year 1 met criteria again during the next year, but 88% met criteria for CD again at least once during the next 3 years. For most boys with CD, the number of symptoms fluctuated above and below the diagnostic threshold from year to year but remained relatively high. Lower socioeconomic status, parental antisocial personality disorder (APD), and attention-deficit hyperactivity disorder were significant correlates of CD in Year 1, but the interaction of parental APD and the boy's verbal intelligence predicted the persistence of CD symptoms over time (i.e., only boys without a parent with APD and with above-average verbal intelligence clearly improved). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early prostate cancer detection and potential for surgical cure in men with poorly differentiated tumors

Postgastrectomy osteopenia is observed generally in humans. Fructooligosaccharides increase the absorption of calcium from the large intestine of healthy rats. Thus, we have examined whether they stimulate calcium absorption and prevent osteopenia in rats following total gastrectomy. Rats were subjected to either a sham surgical operation or Billoth II gastrectomy. Seven rats from each surgical treatment group were fed a control diet, and another seven rats of each treatment group were fed a diet containing fructooligosaccharides (75 g/kg diet) for 4 wk. For 5 d each week, feces were collected, and the calcium and phosphorus contents were measured for calculation of the absorption of these minerals. At the end of the experiment, the rats were killed and bones were collected. The net calcium absorption, calcium content and bone mineral density of the femur and tibia in gastrectomized rats fed the control diet were significantly less than those in sham-operated rats fed control diet. The net calcium absorption in rats fed the fructooligosaccharides diet was greater than that in rats fed control diet. Moreover, dietary fructooligosaccharides prevented the decrease in the calcium content and bone mineral density in gastrectomized rats. Dietary fructooligosaccharides enhanced calcium absorption and prevented the changes indicative of postgastrectomy osteopenia such as decreases in bone calcium content and bone mineral density in gastrectomized rats.     

IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells: Possible Epigenetic Implications Mediated by miRNA

Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed to evaluate whether serum IgG from adult AD patients could modulate the thymic maturation of IL-22-producing T cells and CLA+ T cells of non-atopic infants. Given that miRNAs regulate immune response genes, we evaluated whether miRNA expression is also altered in cultured thymocytes. Thymocytes were cultured with purified IgG from AD patients or control conditions (mock, Intravenous-IgG (IVIg), non-atopic IgG, or atopic non-AD IgG). Using flow cytometry analysis, we assessed the expression of CLA and intracellular levels of IL-4, IFN-γ, and IL-22 on double-positive T cells (DP T), CD4 T cells, or CD8 T cells. We also investigated the frequency of IgG isotypes and their direct interaction with the thymic T cells membrane. The miRNA profiles were evaluated by the Illumina small RNA-seq approach. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Increased frequencies of IL-22 and CLA+ producing CD4+ T cells cultured with IgG of AD patients was seen in non-atopic infant thymocytes compared to all control conditions. No alterations were observed in the frequency of IgG isotypes among evaluated IgG pools. Evidence for a direct interaction between IgG and thymic DP T, CD4 T, and CD8 T cells is presented. The small RNA-seq analysis identified ten mature miRNAs that were modulated by AD IgG compared to mock condition (miR-181b-5p, hsa-miR-130b-3p, hsa-miR-26a-5p, hsa-miR-4497, has-miR-146a, hsa-let-7i-5p, hsa-miR-342-3p, has-miR-148a-3p, has-miR-92a and has-miR-4492). The prediction of the targetome of the seven dysregulated miRNAs between AD and mock control revealed 122 putative targets, and functional and pathway enrichment analyses were performed. Our results enhance our understanding of the mechanism by which IgG can collaborate in thymic T cells in the setting of infant AD.     

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10⁻⁵) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.