Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.     

Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?

Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP.     

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological,Immunohistochemical and Gene Expression Profiles

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.     

On the steady‐state drop size distribution in stirred vessels. Part I: Effect of dispersed phase viscosity

Previous studies on emulsification have used the maximum drop size (d_max) or Sauter mean diameter ( ) to investigate the effect of viscosity on the drop size distribution (DSD), however, these parameters fall short for highly polydispersed emulsions. In this investigation (Part I), the steady‐state DSD of dilute emulsions is studied using of silicon oils with viscosities varying across six orders of magnitude at different stirring speeds. Different emulsification regimes were identified; our modeling and analysis is centered on the intermediate viscosity range where interfacial cohesive stresses can be considered negligible and drop size increases with viscosity. The bimodal frequency distributions by volume were well described using two log‐normal density functions. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3293–3302, 2018     

Ablation behavior and mechanism of boron nitride - magnesium aluminum silicate ceramic composites in an oxyacetylene combustion flame

In the present study, ablation behavior and properties of BN-MAS (magnesium aluminum silicate) composites impinged with an oxyacetylene flame at temperatures up to 3100 °C were investigated. As ablation time ranged from 5 to 30 s, the mass and linear ablation rates increased from 0.0027 g/s and 0.001 mm/s to 0.0254 g/s and 0.087 mm/s, respectively. A SiO₂-rich protective oxide layer formed during the ablation process, which contributed to the oxidation resistance of the composites. Ablation products mainly consisted of magnesium-aluminum borosilicate glass, mullite, spinel and indialite. The thermal oxidation of h-BN during flame ablation and scouring of MAS by high-speed gas flow were the main ablation mechanisms.     

Effect of process parameters on the adhesion strength in two‐component injection molding of thermoset rubbers and thermoplastics

Recently, a novel two‐component injection molding process has been developed for combining thermoplastics with thermoset rubbers. This process is of interest for example when thermoplastic parts include seals which are usually produced out of thermoset rubber. The present study evaluates the influence of different process parameters on the bond strength by means of a half factorial experimental design. The considered process parameters are the mold temperature at the interface, the injection temperature, the injection speed, the holding pressure, and the initial roughness of the thermoplastic part at the later interface. The study indicates a large influence of the mold temperature at the interface. Furthermore, the holding pressure only affects the adhesion strength when it is set too low or when the holding time is too short. The other process parameters have no significant effect on the adhesion strength. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46495.     

Influence of Alkaline Additives and Buffers on Mineral Trapping of CO2 under Mild Conditions

Carbon dioxide (CO₂) gas is the main contributor to climate change. CO₂ storage in underground brines and oil‐field brines by mineral trapping has been considered as a promising alternative in order to reduce CO₂ emissions. However, permanent storage of CO₂ in stable carbonate minerals is greatly dependent on brine pH, being favored over an alkaline pH. The effect of alkaline additives (NaOH, KOH, CaO) and buffer solutions (NaHCO₃/NaOH, Na₂HPO₄/NaOH, NH₄Cl/NH₄OH) on the mineral trapping of CO₂ under mild conditions using a synthetic brine is investigated. The results indicate that both NaOH+NH₄Cl/NH₄OH and KOH+NH₄Cl/NH₄OH mixtures promote precipitation mainly of calcium carbonate (CaCO₃).     

美国绿河油页岩中沥青热解特征及动力学

沥青是油页岩中的重要有机质,也是油页岩中油母质热解产油和气过程的重要中间产物,对其热解研究有利于加深油页岩/油母质热解理解。通过索氏萃取提取出了绿河油页岩中的沥青,并对其进行了不同升温速率下热解实验。基于热重（TGA）数据,使用Friedman法计算了沥青热解的活化能,并通过活化能分布特征,推测沥青热解可能包含三个过程。接着,使用双高斯函数对含有交叠峰的DTG曲线进行反褶积处理,分解成三个峰,依次对应每一个过程。使用最小二乘法获得了这三个过程的活化能、指前因子和反应模型通式,并将获得的通式与四类固态物质热解模型中的11种理想模型进行对比,辨识出上述三个过程均遵循n级反应模型。     

Structure-function studies of an IGF-I analogue that can be chemically cleaved to a two-chain mini-IGF-I

The structure and biological activities of two disulphide isomersof a C-region deletion mutant of insulin-like growth factor-I(IGF-I) which has an Asn–Gly link engineered at the junctionof the A- and B-regions were studied before and after chemicalcleavage. Circular dichroism (CD) spectra and binding affinityto IGF binding protein 3 (IGFBP3) indicated that the treatmentwith hydroxylamine did not disrupt the overall tertiary foldof the hormones. Cleavage restored some binding affinity forthe IGF-I receptor in both isomers and weakly restored the abilityto stimulate incorporation of tritiated thymidine into DNA inNIH 3T3 fibroblasts transfected with the human IGF-I receptor.Cleavage also restored metabolic capacity, as measured by theability of the isomers to promote lipogenesis in isolated ratadipocytes through the insulin receptor. These results are consistentwith the theory that binding of IGF-I to the IGF-I receptorrequires a conformational change similar to that involved ininsulin binding the insulin receptor. The weak affinity forthe IGF-I receptor after cleavage is consistent with the beliefthat residues in the C-region interact with the IGF-I receptor.This structural difference between insulin and IGF-I gives eacha higher binding affinity for its own receptor.