INFLUENZA DEI POLIMORFISMI DI IL-28B E SLC29A1 SULLA RISPOSTA ALLA TERAPIA CON INTERFERONE PEGILATO E RIBAVIRINA IN PAZIENTI COINFETTI HIV-HCV

HCV coinfection is the major health complication for HIV patients. More frequently than some years ago their death is related to HCV induced end-stage liver disease rather than AIDS induced by HIV. The reason for this is the significant progress in development of antiretroviral therapy allowing HIV infected patients the lifespan close to the range of uninfected people, on the other hand higher than in HCV monoinfected patients susceptibility to develop liver diseas and low adherence to the anti-HCV therapy regimen resulting that only about 60% of them can be cured. Additionally, it is now well established that in patients monoinfected with HCV as well as those who are coinfected with HIV, spontaneous or therapy induced clearance of the HCV is associated with single nucleotide polymorphism near or in the IL-28b gene. IL-28b gene SNPs together with HCV genotype, viral load, ethnicity, and age are among independent pretreatment predictors of SVR among HCV monoinfected patients, whereas during treatment the best predictor of SVR is viral dicline at 4th week after therapy initiation. The mechanism through which SNP\u2019s near/in the IL-28b gene can affect the spontaneous or therapy induced clearance of the virus are not know. Some studies show the genotype dependent mRNA expression of IL-28b in peripheral blood mononuclear cells of healthy and HCV infected patients. In our study we have first determined the distribution of genotypes for 5 different SNP\u2019s of which 4 are located in intronic part near IL-28a/b genes and include: rs12979860, rs809917, rs12980275, rs11881222 and 1 is located in equilibrative nucleoside transporter 1 (ENT1) gene which is involved in cellular uptake of ribavirin. The distribution of genotypes of these SNP\u2019s could let us understand the reasons for which some patients do not clear or respond to the anti-HCV therapy but also to understand the kinetics of suppression or not of viral load. Through analyses of IL-28a and IL-28b gene expression in PBMC of studied groups we have also attempted to understand if the tested SNP\u2019s arround the IL-28a/b genes can determine the expression of these cytokines and thus the predispositions of some people to better clear the HCV virus. What we have optained can be summarized in the following steps: In group of Italian population of HCV/HIV coinfected patients we found significant association between genetic polymorphisms near IL-28a/b genes and HCV clearance. We determined the allels of studied SNP\u2019s that predispose the host to clear the virus; In group of patients who needed the support the anti-HCV therapy we found that the same genetic SNP\u2019s as for patients who cleared the virus determine the sustained virological response. Additionaly in achiving this status were important the HCV genotype, HCV load, and cART. We found also genetic association between HCV load detection at 3rd month after application of therapy and SNP in ENT1 gene implying possible effect of use of ribavirin in the therapy. IL-28a and IL-28b gene expression analyses showed that IL-28a is in general expressed at higher level than in IL-28b in any of tested groups. However, in contrast to IL-28a, IL-28b is downregulated in patients who do not respond to the therapy in comparison to those with SVR. Moreover, expression of IL-28b is higher among those HCV patients who carry preferential for HCV spontaneous clearance and therapy response alleles of tested SNP\u2019s near IL28a/b genes. This observation is not evident among healthy patients suggesting that different levels of expression of IL-28b between subgroups of HCV patients are the result of secondary causes

Neural Correlates in Learning Disabilities

In recent years, researchers have done significant advances on the study of learning disabilities in particular in terms of comprehension of cognitive and anatomical mechanisms. The understanding of neural mechanism of learning disabilities is useful for their management and cognitive treatment. The advent of functional neuroimaging methods has also identified anatomical networks and neurological learning systems that have contributed to knowledge of neurobiology of learning deficits. On the other side, neuropsychological assessment, with comprehensive test or specific cognitive tasks, has proved to be useful to analyze specific cognitive deficits to find potential targets of intervention for cognitive compensation. In this chapter the author summarizes major scientific advances in particular in the study of neuroanatomical mechanism based on structural and functional neuroimaging of children with learning disorders, developmental disorders, and language impairment, in particular with dyslexia which is one of the most common learning disabilities

Introductory Chapter: Definition of Cognitive Behavioral Therapy and Its Principal Applications

n/

Neuropsychological Assessment of Children with Learning Disabilities

Learning disabilities are a heterogeneous and common group of disorders that have a relevant impact on children’s academic function. The most common learning disorders consist of dyslexia, dyscalculia, dysgraphia or other non-verbal learning disorders. These disorders are commonly associated with neurological or behavioral disorders such as attention-deficit hyperactivity disorders. Understanding of cognitive and mental problems of children with learning disorders is an interesting challenge, and various approaches have been applied for their study, including medical, genetic, educational, epidemiologic and experimental psychologist. Nowadays, clinical neuropsychological approach, which is based on neurocognitive models, is one of the best existing models for description and interpretation of learning disorders. This approach assumes that there is a strong relationship between the various learning deficits and brain functioning. This paper consists of a descriptive review about components of a specialized neuropsychological approach that can be applied for the assessment of children with learning disabilities

Clinical Applications of Brain Mapping in Epilepsy

EEG brain mapping is a neurophysiological technique based on computer-assisted analysis of conventional EEG. This technique, generally consisting in quantitative analysis of EEG (QEEG), includes topographic displays of frequency or voltage, statistical comparison to normal values and discriminant analysis. QEEG assessment still remains controversy about its clinical role. QEEG topographic analysis could be useful in many neurological diseases: in cerebrovascular disease EEG analysis is useful since EEG parameters are highly correlates with regional blood and metabolism; in degenerative disease (as dementia or encephalopathies) quantitative EEG frequency analysis could suggest an organic base of the disorder even if it is not able to distinguish between the types of dementia. QEEG techniques are also potentially useful in identifying anomalies in patients with cerebral trauma or in children with cognitive disorders. In the field of epilepsy EEG brain mapping could help clinics to detect spikes, locate an epileptic focus and suggest the type of epilepsy. In this chapter author describes principles of EEG brain mapping and its potential applications in particular in the epileptic field

Psychometry in Dementia

Grow in aging has led to an increasing number of people presenting with cognitive impairment and dementia. Most forms of dementia are classified by means of morphological techniques, assays of biomarkers in cerebrospinal fluid and neuropsychological assessment, into degenerative forms, dementia of vascular type and dementia secondary to other conditions. It is very difficult to make a clear-cut diagnosis of the different types of dementia by means of clinical methods. However, many psychometric tests play a prominent role in screening and evaluation of patients with cognitive impairment. Some tools can help clinicians in differential diagnosis among the various forms of dementia such as the ones that assess clinical aspects, tests that focus on specific cognitive areas or behavioral inventories. Still nowadays, there is not a consensus about the best strategies for screening and assessment of cognitive impairment among elderly subjects. The purpose of this chapter is to make a review of the screening tools and psychometric test instruments that healthcare professionals can use for screening and neuropsychological assessment of geriatric individuals with cognitive disorders to help diagnosis of dementia and to make differential diagnosis of the most common forms of dementia

Composite intersection reinforcement

An assembly and method for manufacturing a composite reinforcement for unitizing a structure are provided. According to one embodiment, the assembly includes a base having a plurality of pins extending outwardly therefrom to define a structure about which a composite fiber is wound to define a composite reinforcement preform. The assembly also includes a plurality of mandrels positioned adjacent to the base and at least a portion of the composite reinforcement preform, and a cap that is positioned over at least a portion of the plurality of mandrels. The cap is configured to engage each of the mandrels to support the mandrels and the composite reinforcement preform during a curing process to form the composite reinforcement

Composite Intersection Reinforcement

An assembly and method for manufacturing a composite reinforcement for unitizing a structure are provided. According to one embodiment, the assembly includes a base having a plurality of pins extending outwardly therefrom to define a structure about which a composite fiber is wound to define a composite reinforcement preform. The assembly also includes a plurality of mandrels positioned adjacent to the base and at least a portion of the composite reinforcement preform, and a cap that is positioned over at least a portion of the plurality of mandrels. The cap is configured to engage each of the mandrels to support the mandrels and the composite reinforcement preform during a curing process to form the composite reinforcement