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-linear diffusion of image noise with minimal iterativity

Non-linear diffusion (ND) is an iterative difference equation used in several image processing applications such as denoising, segmentation, or compression. The number of iterations required to achieve optimal processing can be very high, making ND not suitable for real-time requirements. In this paper, we study how to reduce complexity of ND so as to achieve minimal number of iterations for real-time image denoising. To do this, we first study the relations between parameters of the iterative equation: the number of iterations, the time step, and the edge strength. We then proceed by estimating the minimally required number of iterations to achieve effective denoising. Then, we relate the edge strength to the number of iterations, to noise, and to the image structure. The resulted minimal iterativity ND is very fast, while still achieves similar or better noise reduction compared to related ND work. This paper also shows how the proposed spatial filter is suitable for structure-sensitive object segmentation and temporal noise reduction.     

Finite multidimensional behaviors

We study finitely generated and finite systems defined by linear partial difference equations with constant coefficients in a Noetherian ring. The two notions coincide for finite rings, and we show that all finite systems exhibit certain periodicity properties. For the particular case of systems over the ring of integers modulo m?>?1, which is important in coding theory, a method is given for determining the number of trajectories, using Gr?bner basis techniques.     

Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation

Gelatin is a very promising matrix material for in vitro cell culture and tissue engineering, e.g. due to its native RGD content. For the generation of medical soft tissue implants chemical modification of gelatin improves the mechanical properties of gelatin hydrogels and the viscous behavior of gelatin solutions for liquid handling. We present a systematic study on the influence of high degrees of methacrylation on the properties of gelatin solutions and photo-chemically crosslinked hydrogels. Changes from shear thinning to shear thickening behavior of gelatin solutions were observed depending on mass fraction and degree of methacrylation. Degrees of swelling of crosslinked hydrogels ranged from 194 to 770?% and storage moduli G′ from 368 to 5?kPa, comparable to various natural tissues including several types of cartilage. Crosslinked gels proofed to be cytocompatible according to extract testings based on DIN ISO 10933-5 and in contact with porcine chondrocytes.     

Distributed coordination of emergency medical service for angioplasty patients

In this paper we study the coordination of Emergency Medical Service (EMS) for patients with acute myocardial infarction with ST-segment elevation (STEMI). This is a health problem with high associated mortality. A “golden standard” treatment for STEMI is angioplasty, which requires a catheterization lab and a highly qualified cardiology team. It should be performed as soon as possible since the delay to treatment worsens the patient’s prognosis. The decrease of the delay is achieved by coordination of EMS, which is especially important in the case of multiple simultaneous patients. Nowadays, this process is based on the First-Come-First-Served (FCFS) principle and it heavily depends on human control and phone communication with high proneness to human error and delays. The objective is, therefore, to automate the EMS coordination while minimizing the time from symptom onset to reperfusion and thus to lower the mortality and morbidity resulting from this disease. In this paper, we present a multi-agent decision-support system for the distributed coordination of EMS focusing on urgent out-of-hospital STEMI patients awaiting angioplasty. The system is also applicable to emergency patients of any pathology needing pre-hospital acute medical care and urgent hospital treatment. The assignment of patients to ambulances and angioplasty-enabled hospitals with cardiology teams is performed via a three-level optimization model. At each level, we find a globally efficient solution by a modification of the distributed relaxation method for the assignment problem called the auction algorithm. The efficiency of the proposed model is demonstrated by simulation experiments.     

Analysis of the musculoskeletal system of the hand and forearm during a cylinder grasping task

Musculoskeletal disorders of the hand are mostly due to repeated or awkward manual tasks in the work environment and are considered a public health issue. To prevent their development, it is necessary to understand and investigate the biomechanical behavior of the musculoskeletal system during the movement. In this study a biomechanical analysis of the upper extremity during a cylinder grasping task is conducted by using a parameterized musculoskeletal model of the hand and forearm. The proposed model is composed of 21 segments, 28 musculotendon units, and 20 joints providing 24 degrees of freedom. Boundary conditions of the model are defined by the three-dimensional coordinates of 43 external markers fixed to bony landmarks of the hand and forearm and tracked with an optoelectronic motion capture system. External marker positions from five healthy participants were used to test the model. A task consisting of closing and opening fingers around a cylinder 25 mm in diameter was investigated. Based on experimental kinematic data, an inverse dynamics process was performed to calculate output data of the model (joint angles, musculotendon unit shortening and lengthening patterns). Finally, based on an optimization procedure, joint loads and musculotendon forces were computed in a forward dynamics simulation. Results of this study assessed reproducibility and consistency of the biomechanical behavior of the musculoskeletal hand system.     

Influence of dietary vitamin C and selenium,alone and in combination,on the composition and oxidative stability of meat of broilers

Information on the combined effect of dietary vitamin C and Se on the composition and oxidative stability of meat of broilers is not available in the literature. In the present experiment, male broiler chickens were fed a maize–wheat–soya diet supplemented with vitamin C at 280 and 560 mg/kg of diet, and Se (sodium selenite or selenised yeast; Se) at 0.3 mg/kg for 5 weeks. After slaughter, samples of thigh meat were analysed. The supplementation of diets with vitamin C or Se increased the protein concentration of the meat at the expense of fat. Vitamin C supplementation increased the vitamin C content of the meat in a dose-dependent manner and decreased the vitamin A concentration in the meat of broilers fed diets with sodium selenite or without a Se supplement. In the meat of the broilers that were fed these diets, the vitamin C decreased the lipid oxidation in meat that was stored for 5 days. No sparing effect of vitamin C was apparent on the amount of vitamin E in the meat. Selenised yeast was more effective in the enrichment of meat with Se than was selenite. Both Se sources increased the activity of glutathione peroxidase and the oxidative stability of the meat.