HLA-associated drug hypersensitivity and the prediction of adverse drug reactions

Adverse drug reactions are an important cause of morbidity and mortality and constitute the leading reason of drug withdrawal from the market. Besides classical reactions that are related to pharmacologic activity of the drug, some reactions are unpredictable, not dose dependent, and seem to occur in genetically predisposed individuals. The majority of this reaction is immunologically driven and they are referred to as hypersensitivity reactions. A growing number of studies provided evidences that specific HLA alleles increase the risk of developing hypersensitivity drug reactions. In this context, drug hypersensitivities that have more robust pharmacogenetic data include abacavir hypersensitivity syndrome and severe cutaneous adverse reactions induced by allopurinol and carbamazepine

The three-dimensional easy morphological (3-DEMO) classification of scoliosis, part II: repeatability

BACKGROUND: In the first part of this study we proposed a new classification approach for spinal deformities (3-DEMO). To be valid, a classification needs to overcome the repeatability issue which is inherent both in the used classificatory system and in the measured object. AIM: The aim of this study is to present procedures and results obtained within the repeatability of 3-DEMO classification for scoliosis analysis. METHOD: We acquired the data of 100 pathological and 20 normal spines with an optoelectronic system (AUSCAN) and of two dummies with simulated spine deformity. On the obtained 3D reconstruction of the spine, we considered the coronal view with a spinal reference system (Top View) and its three related parameters, defined in part I, constituting the 3-DEMO classification. We calculated the repeatability coefficient for the subjects (two acquisitions for each subject with a time interval of 26 ± 12 sec), whereas we evaluated the system measurement error calculating the standard deviation of 50 consecutive acquisitions for each dummy. RESULTS: Comparing the results of the two types of acquisition, it emerged that the main part of parameters variability was due to postural adjustments The proportion of agreement for the 3-DEMO parameters gives a k value above 0.8; almost 10% of patients changed classification because of postural adjustments, but none had a "mirror-like" variation nor a change in more of one parameter at a time Repeatability coefficient is lower than the previously calculated normative limits. DISCUSSION: The 3-DEMO classification has a high repeatability when evaluated with an optoelectronic system such as the AUSCAN System, whose systematic error is very low. This means that the implied physiological phenomenon is consistent and overcomes the postural variability inherent in the measured object (normal or pathological subject)

Postural effects of symmetrical and asymmetrical loads on the spines of schoolchildren

The school backpack constitutes a daily load for schoolchildren: we set out to analyse the postural effects of this load, considering trunk rotation, shoulder asymmetry, thoracic kyphosis, lumbar lordosis, and sagittal and frontal decompensation from the plumbline. A group of 43 subjects (mean age = 12.5 ± 0.5 years) were considered: average backpack loads and average time spent getting to/from home/school (7 min) had been determined in a previous study conducted on this population. Children were evaluated by means of an optoelectronic device in different conditions corresponding to their usual everyday school backpack activities: without load; bearing 12 (week maximum) and 8 (week average) kg symmetrical loads; bearing an 8 kg asymmetrical load; after fatigue due to backpack carrying (a 7-minute treadmill walking session bearing an 8 kg symmetrical load). Both types of load induce changes in posture: the symmetrical one in the sagittal plane, without statistical significant differences between 8 and 12 kg, and the asymmetrical one in all anatomical planes. Usual fatigue accentuates sagittal effects, but recovery of all parameters (except lumbar lordosis) follows removal of the load. The backpack load effect on schoolchildren posture should be more carefully evaluated in the future, even if we must bear in mind that laws protect workers to carry heavy loads but not children, and results in the literature support the hypothesis that back pain in youngsters is correlated with back pain in adulthoo

Static analysis for dummies: Experiencing LiSA

Semantics-based static analysis requires a significant theoretical background before being able to design and implement a new analysis. Unfortunately, the development of even a toy static analyzer from scratch requires to implement an infrastructure (parser, control flow graphs representation, fixpoint algorithms, etc.) that is too demanding for bachelor and master students in computer science. This approach difficulty can condition the acquisition of skills on software verification which are of major importance for the design of secure systems. In this paper, we show how LiSA (Library for Static Analysis) can play a role in that respect. LiSA implements the basic infrastructure that allows a non-expert user to develop even simple analyses (e.g., dataflow and numerical non-relational domains) focusing only on the design of the appropriate representation of the property of interest and of the sound approximation of the program statements

Case Report: Rehabilitation After Platelet-Rich Growth Factors\u2019 Intra-Articular Injections for Knee Osteoarthritis: Two Case Reports of a Home-Based Protocol

Knee osteoarthritis (KOA) is a chronic progressive disease that can cause pain, functional impairment, and ultimately disability. A novel and promising therapeutic approach to KOA is the so-called regenerative medicine, a set of procedures designed to harness tissue regenerative capacity and optimize functional recovery. Increasing evidence points out that platelet-rich plasma (PRP) intra-articular injections can decrease pain and improve functional abilities in KOA patients. In the present case reports, we analyze two patients who were treated with PRP injections coupled with a posttreatment home-based rehabilitation program. The two patients were selected to represent two different populations: patient 1 was an 85-year-old with severe impairment of functional abilities, while patient 2 was a younger (59 years old) and more active patient. The protocol consisted in a series of exercise to be performed at home, during the five days following PRP injection for two consecutive weeks (10 days in total). The exercises were designed to reduce the inflammation after the injection, enhance the proprioceptive control of the treated lower limb, and strengthen hip and knee flexors and extensors, mainly by isometric work. Results were evaluated at two time points: before and 2 months after the first PRP injection. The outcomes considered were as follows: visual analog scale for pain, EuroQol 5 dimensions questionnaire, Tegner Activity Scale for functioning, and Knee Injury and Osteoarthritis Outcome Score (KOOS). Both patients did not report any side effects from the treatment. Improvement in patient 1 was drastic at the two months follow-up as far as pain and functional abilities are concerned. Patient 2\u2019s improvement was less evident, probably due to the higher starting point in both pain and functionality. Overall, the developed program seemed safe and was tolerated by the patients analyzed in the study, who performed it with good compliance

Twinning Automata and Regular Expressions for String Static Analysis

In this paper we formalize TARSIS, a new abstract domain based on the abstract interpretation theory that approximates string values through finite state automata. The main novelty of TARSIS is that it works over an alphabet of strings instead of single characters. On the one hand, such an approach requires a more complex and refined definition of the widening operator, and the abstract semantics of string operators. On the other hand, it is in position to obtain strictly more precise results than state-of-the-art approaches. We implemented a prototype of TARSIS, and we applied it to some case studies taken from some of the most popular Java libraries manipulating string values. The experimental results confirm that TARSIS is in position to obtain strictly more precise results than existing analyses

Nitrogen starvation and nitrate or ammonium availability differently affect phenolic composition in green and purple basil

Basil (Ocimum basilicum L.) comprises green and purple cultivars, worldwide cultivated and appreciated for high contents of rosmarinic acid and anthocyanins, respectively. Although nitrogen (N) fertilization is needed for high yields, in basil it could have detrimental effects on the accumulation of phenolic compounds. In this study, plants of the cultivars 'Italiano Classico' (green) and 'Red Rubin' (purple) were grown in hydroponics and subjected to different nutritional treatments, consisting in N starvation, and nitrate (NO3 12) or ammonium (NH4+) nutrition. Plant growth and nutritional status, estimated by the contents of NO3 12, NH4+, and amino acids in roots and leaves, were evaluated and put in relation with quality traits of basil leaves, such as chlorophyll content, antioxidant capacity, total phenols, the activity of phenylalanine ammonia-lyase, and the concentrations of individual (poly)phenolic acids and flavonoids. This study reveals that N starvation, as well as the availability of the two inorganic N forms, differently affect the phenolic composition in the two cultivars. Compared to plants grown in NO3 12 availability, in NH4+ availability, green basil showed a higher content of (poly)phenolic acids, while in purple basil, an increase in the contents of anthocyanins was detected. Overall, the study suggests that the management of NH4+ supply could contribute to enhance crop quality in hydroponics, and provides new knowledge about the relationship between N nutrition and phenolic metabolism in basil

Atmospheric fluctuations below 0.1 Hz during drift-scan solar diameter measurements

Measurements of the power spectrum of the seeing in the range 0.001-1 Hz have been performed in order to understand the criticity of the transits' method for solar diameter monitoring.Comment: 3 pages, 3 figures, proc. of the Fourth French-Chinese meeting on Solar Physics Understanding Solar Activity: Advances and Challenges, 15 - 18 November, 2011 Nice, Franc