Swelling Deswelling Behavior of PS‐PNIPAAM Copolymer Particles and PNIPAAM Brushes Grafted from Polystyrene Particles & Monoliths

Two sets of emulsion particles have been synthesized. In the first set, surfactant free emulsion was used to directly synthesize PS‐PNIPAAM copolymer particles. In the second set, polystyrene particles with an ATRP initiator shell were first synthesized and subsequently grafted with PNIPAAM brushes. Swelling/deswelling behavior of both sets of particles was studied with respect to temperature and time. Monoliths with two different porosities were also formed by grafting and crosslinking of PNIPAAM chains on the aggregated particles and characterized. In all cases, swelling kinetics is sufficiently fast to use these supports for separation driven by temperature changes only. However, hindrance and cross‐linking is sensibly reducing the material performance.

     

High‐density polyethylene reinforced with submicron titania particles

Submicron titania particles were prepared by means of two different synthetic procedures in order to obtain different particle size (diameter ranging from 20 to 350 nm), shapes, and morphologies (amorphous or crystalline). Titania particles were surface modified with octadecylsilane in order to improve their compatibility with respect to polymeric matrices. High‐density polyethylene (HDPE)–titania composites were prepared by melt blending by using an internal mixer. The obtained composites were mechanically characterized in quasi static and creep tensile conditions. The presence of submicron titania particles (1 %vol) led to a significant increase of elastic modulus (20–25%) with respect to the unreinforced HDPE together with a slight increase of yield stress and a decrease of ultimate elongation. An interesting reduction for both elastic and viscoelastic creep compliance components was also evidenced. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers     

Characterization of Low‐Molecular‐Weight PLA using HPLC

HPLC is applied and assessed as an effective tool to investigate both the production of PLA by polycondensation and its corresponding degradation. A new HPLC calibration procedure, through which it is possible to fully characterize LMW PLA samples by determining the concentration of each individual oligomer, is developed. A comparison between HPLC, ¹H NMR spectroscopy and non‐aqueous solution titration is also reported in order to confirm the reliability of the proposed method. Finally, the proposed analytical technique is applied to monitor the development of a polycondensation reaction performed at 150 °C and 133.3 mbar for 12 h.

     

Scratch Resistance Enhancement of Polymer Coatings

This review presents the state of the art regarding the improvement of scratch resistance of polymeric coatings. In particular, our attention is focused on the effect of inorganic nanometric fillers on the scratch resistance of organic coatings. Two main strategies are described for the achievement of such nanostructured hybrid organic/inorganic coatings: either a top‐down or a bottom‐up approach.

     

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.     

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (ATM, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, wild type for germline mutation in BRCA1/2 genes. The analysis was extended to 5′UTR and 3′UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients. The screening was performed through NGS target resequencing on the Illumina platform MiSeq. 8.7% of the patients analyzed is carriers of class 5/4 coding variants in the ATM (3.6%), BRIP1 (1.6%), CHEK2 (1.8%), PALB2 (0.7%), RAD51C (0.4%), RAD51D (0.4%), and TP53 (0.2%) genes, while variants of uncertain pathological significance (VUSs)/class 3 were identified in 9.1% of the samples. In intron-exon junctions and in regulatory regions, variants were detected respectively in 5.1% and in 32.5% of the cases analyzed. The average age of disease onset of 44.4 in non-coding variant carriers is absolutely similar to the average age of disease onset in coding variant carriers for each proband’s group with the same cancer type. Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a PTEN 3′UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.     

Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.