1,064 research outputs found
Childhood Adrenocortical Tumours: a Review
Childhood adrenocortical tumour (ACT) is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6%) or mixed with Cushing's syndrome (42.0%) was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate
The Italian Consensus Conference on Pain in Neurorehabilitation
Pain is frequent in several neurological conditions, such as stroke, Parkinson’s disease, multiple sclerosis, diabetic neuropathy, but it is often underestimated and therefore untreated or not successfully treated. Pain reduces quality of life, it may be the cause of adaptive disorders (such as anxiety and depression) and, in patients undergoing rehabilitation, it may negatively impact rehabilitation procedures and hamper the outcome. Unfortunately, there are no significant data regarding the impact of pain in neurorehabilitation patients and what would be the impact of an appropriate pain treatment on rehabilitation outcome. Accordingly, there are no guidelines providing indications on how to treat pain in patients with pain during rehabilitation treatment and thereafter. Given this background, and to comply with the Italian law 38 released on 2010 by the Italian Ministry of Health to guarantee adequate care and treatment of patients with pain both in hospital and in primary care, the Italian Society for Neurological Rehabilitation (SIRN) along with the Italian Society for Physical and Rehabilitative Medicine (SIMFER), promoted a work-in-progress platform, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPNR)
MATHEMATICAL PLURALISM AND SOME GENERIC ABSOLUTENESS RESULTS IN SET THEORY: A PHILOSOPHICAL INQUIRY
The forcing technique was discovered by Paul Cohen in the early sixties. Since then forcing has appeared to be a very powerful tool to provide independence results in Set theory. Actually, because of the foundational role played by Set theory with regard to the rest of classical mathematics, and because of the possibility to mimic from the standard axiomatic basis of Set theory, ZFC, the proof of the existence of almost any mathematical object, forcing has been applied to different areas of mathematics revealing to us the undecidability of many different important questions connected with different branches of mathematics.
Given the pervasive presence of the independence phenomenon in Set theory determined by forcing, a natural philosophical question arises: is forcing the ultimate horizon of Set theory, or is it (as a source of undecidability) to be considered as a pathology that needs to be neutralised? A special kind of results in Set theory, known in literature as generic absoluteness results, give mathematical substance to the perspective that the real challenge that the discovery of the forcing technique places to the set theorist, as well as to the philosopher of mathematics, goes beyond the idea that the right answer to questions such as the Continuum Hypothesis is given by computing the precise extent of their undecidability. In fact, when it is possible to relieve generic absoluteness for a certain mathematical structure, a different framework appears where forcing can be exploited and, so we may say, integrated into the practice of the mathematician as a strong tool for proving theorems. In chapter 1 of my dissertation I recall some main aspects of the forcing technique developed following the Boolean valued-models approach introduced by Scott, Solovay, and Vopenka starting from 1965. In chapters 2 and 3 I analyze some main motivations behind Viale's and Woodin's alternative strategies for producing generic absoluteness for the structure at the level of the Continuum problem. I try to stress, in particular, the essential use of the so-called forcing axioms that is inherent Viale's generic absoluteness results and that, to some extent, conflicts with Woodin's choice to introduce a strong logic as the appropriate setting for studying the possibility of generic absoluteness at the level of the Continuum problem. In chapter 4 I open the philosophical discussion and I try to correlate the pure mathematical phenomenon of generic absoluteness described in chapters 2 and 3 to the more general philosophical debate concerning the question of Pluralism in Set theory and the search for new axioms. Insofar as we are interested in spell out Viale's and Woodin's absoluteness results in terms of the right axiomatisation for the structure theory where the Continuum problem is expressible, I try to sketch an argument according to which the possibility to unify the two distinct theories offered by Viale and Woodin emerges as one of notable philosophical importance
kinematic and neurophysiological models future applications in neurorehabilitation
This paper emphasizes the importance of developing kinematic and neurophysiological methods for evaluating motor and functional recovery in the field of neurorehabilitation. From a review of the literature, it is concluded that optoelectronic motion analysis and neurophysiological techniques, such as the study of nociceptive withdrawal reflex, might constitute useful applications for future research
Caracterização espectrorradiométrica de minerais e rochas sedimentares.
bitstream/item/33610/1/documento-172.pd
Morc1 knockout evokes a depression-like phenotype in mice
Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress
Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control.
Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache ( MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine ( EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings
Physical Exercise Affects Adipose Tissue Profile and Prevents Arterial Thrombosis in BDNF Val66Met Mice
Adipose tissue accumulation is an independent and modifiable risk factor for cardiovascular disease (CVD). The recent CVD European Guidelines strongly recommend regular physical exercise (PE) as a management strategy for prevention and treatment of CVD associated with metabolic disorders and obesity. Although mutations as well as common genetic variants, including the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, are associated with increased body weight, eating and neuropsychiatric disorders, and myocardial infarction, the effect of this polymorphism on adipose tissue accumulation and regulation as well as its relation to obesity/thrombosis remains to be elucidated. Here, we showed that white adipose tissue (WAT) of humanized knock-in BDNFVal66Met (BDNFMet/Met) mice is characterized by an altered morphology and an enhanced inflammatory profile compared to wild-type BDNFVal/Val. Four weeks of voluntary PE restored the adipocyte size distribution, counteracted the inflammatory profile of adipose tissue, and prevented the prothrombotic phenotype displayed, per se, by BDNFMet/Met mice. C3H10T1/2 cells treated with the Pro-BDNFMet peptide well recapitulated the gene alterations observed in BDNFMet/Met WAT mice. In conclusion, these data indicate the strong impact of lifestyle, in particular of the beneficial effect of PE, on the management of arterial thrombosis and inflammation associated with obesity in relation to the specific BDNF Val66Met mutation
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