Il fatto educativo // The educational fact

O academicismo trancafiou a Universidade na sua autorreferencialidade. Raramente se acha um jovem licenciado que descreve a importância e a utilidade dos próprios estudos superiores nas contingências novas que a vida e o trabalho o levam a enfrentar: a Universidade é “diferente” da vida. As ciências da educação, se assumissem claramente, também a partir do próprio estatuto, a concepção de serem “instrumentos” a entregar a mãos competentes, a pessoas autênticas e com rosto humano, poderiam oferecer uma grande contribuição à pessoa-educador como auxílio para o discernimento dos modos e das possibilidades de companhia à pessoaeducando no seu crescimento e no seu caminho não sisífico em direção à meta ideal! Contrariamente, acontece de ter de constatar quanto inútil para tal fim seja a competência que adquirem, melhor, quanto perniciosa é a ação que sai destes “educadores especializados”: um endurecimento geral, um achatamento indolente no cotidiano, a perda de toda idealidade, a inversãode toda realidade! Então tudo está perdido na sociedade cientificada? A resposta, estranha para muitos, mas verdadeira: a destruição não aconteceu pela persistência nela de costumes morais tradicionais na vida cotidiana das pessoas reais, as pessoas continuam vivendo e manifestando o mal-estar existencial e o desejo de algo que parece ter fugido, mas que não está completamente perdido. Tudo é possível, então, se nos pomos na perspectiva de busca humilde, leal e apaixonada das molas capazes de lançar o homem a desejar ir além do seu próprio presente atual, buscando caracterizar a própria tarefa educativa, não como atuação inteligente e interesseira deteorias na prática quotidiana, mas como encontro pessoal e real no qual cada um cresce e amadurece a sua personalidade: o encontro com pessoas verdadeiras e autênticas faz surgir o amor por esta humanidade e o desejo de transcendê-la como ideal e caminho de vida. A experiência de um encontro entre humanidades verdadeiras pode fazer renascer o ideal e despertar o desejo de realizá-lo

Measles virus-specific CD4 T-cell activity does not correlate with protection against lung infection or viral clearance.

Acute measles in children can be prevented by immunization with the live attenuated measles vaccine virus. Although immunization is able to induce CD4 and CD8 T cells as well as neutralizing antibodies, only the latter have been correlated with protective immunity. CD8 T cells, however, have been documented to be important in viral clearance in the respiratory tract, whereas CD4 T cells have been shown to be protective in a mouse encephalitis model. In order to investigate the CD4 T-cell response in infection of the respiratory tract, we have defined a T-cell epitope in the hemagglutinin (H) protein for immunization and developed a monoclonal antibody for depletion of CD4 T cells in the cotton rat model. Although the kinetics of CD4 T-cell development correlated with clearance of virus, the depletion of CD4 T cells during the primary infection did not influence viral titers in lung tissue. Immunization with the H epitope induced a CD4 T-cell response but did not protect against infection. Immunization in the presence of maternal antibodies resulted in the development of a CD4 T-cell response which (in the absence of neutralizing antibodies) did not protect against infection. In summary, CD4 T cells do not seem to protect against infection after immunization and do not participate in clearance of virus infection from lung tissue during measles virus infection. We speculate that the major role of CD4 T cells is to control and clear virus infection from other affected organs like the brain

Heart Rate Fractality Disruption as a Footprint of Subthreshold Depressive Symptoms in a Healthy Population

Psychopathology (and depression in particular) is a cardiovascular risk factor independent from any co-occurring pathology. This link is traced back to the mind-heart-body connection, whose underlying mechanisms are still not completely known. To study psychopathology in relation to the heart, it is necessary to observe the autonomic nervous system, which mediates among the parts of that connection. Its gold standard of evaluation is the study of heart rate variability (HRV). To investigate whether any association exists between the HRV parameters and sub-threshold depressive symptoms in a sample of healthy subjects

Angiomyolipoma Have Common Mutations in TSC2 but No Other Common Genetic Events

Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both in association with Tuberous Sclerosis Complex (TSC) and independent of that disorder. Previous studies on the molecular genetic alterations that occur in angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen tissue was available from a consecutive surgical series. Seven of 8 samples subjected to RT-PCR-cDNA sequencing showed mutations in TSC2; none showed mutations in TSC1 or RHEB. Six of the seven mutations were deletions. We searched for 983 activating and inactivating mutations in 115 genes, and found none in these tumors. Similarly analysis for genomic regions of loss or gain, assessed by Affymetrix SNP6.0 analysis, showed no abnormalities. Loss of heterozygosity in the TSC2 region was commonly seen, except in patients with low frequency TSC2 mutations. We conclude that sporadic renal angiomyolipoma usually have mutations in TSC2, but not TSC1 or RHEB, and have no other common genomic events, among those we searched for. However, chromosomal translocations and gene fusion events were not assessed here. TSC2 inactivation by mutation is a consistent and likely necessary genetic event in the pathogenesis of most angiomyolipoma

Real-Time Monitoring of Tumorigenesis, Dissemination, & Drug Response in a Preclinical Model of Lymphangioleiomyomatosis/Tuberous Sclerosis Complex

Background: TSC2-deficient cells can proliferate in the lungs, kidneys, and other organs causing devastating progressive multisystem disorders such as lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC). Preclinical models utilizing LAM patient-derived cells have been difficult to establish. We developed a novel animal model system to study the molecular mechanisms of TSC/LAM pathogenesis and tumorigenesis and provide a platform for drug testing. Methods and Findings: TSC2-deficient human cells, derived from the angiomyolipoma of a LAM patient, were engineered to co-express both sodium-iodide symporter (NIS) and green fluorescent protein (GFP). Cells were inoculated intraparenchymally, intravenously, or intratracheally into athymic NCr nu/nu mice and cells were tracked and quantified using single photon emission computed tomography (SPECT) and computed tomography (CT). Surprisingly, TSC2-deficient cells administered intratracheally resulted in rapid dissemination to lymph node basins throughout the body, and histopathological changes in the lung consistent with LAM. Estrogen was found to be permissive for tumor growth and dissemination. Rapamycin inhibited tumor growth, but tumors regrew after the drug treatment was withdrawn. Conclusions: We generated homogeneous NIS/GFP co-expressing TSC2-deficient, patient-derived cells that can proliferate and migrate in vivo after intratracheal instillation. Although the animal model we describe has some limitations, we demonstrate that systemic tumors formed from TSC2-deficient cells can be monitored and quantified noninvasively over time using SPECT/CT, thus providing a much needed model system for in vivo drug testing and mechanistic studies of TSC2-deficient cells and their related clinical syndromes

Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672

ANIMAL MODELS FOR THE STUDY OF LEISHMANIASIS IMMUNOLOGY

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease

Alasdair MacIntyre: Persona e Personalismo

MacIntyre è il grande avversario lottatore contro modernità e post-modernità. Egli scopre, ed argomenta, che all'origine della affermazione "moderna" c'è una grande truffa fondata sulla presunzione di liberarsi dalla soggezione alla storia, intesa sia come Tradizione sia come metodo con una sua epistemologia per comprendere l'uomo e il suo operare. L'epilogo di tale pretesa è sotto gli occhi: un razionalismo autoreferenziale che non ha più contatto con la realtà e che proprio per questo si riduce a delirio di onnipotenza o di potenza decaduta per resistenza indebita di storia e tradizioni "portatrici solo di oscurantismo!". La realtà porta, invece, a scoprire l'identità dell'uomo come «io» contestualizzato, che nasce da una storia, una storia di amore, e si realizza in un contesto di condizioni e condizionamenti, con cui bisogna sempre fare i conti se si desidera essere lealmente attenti a cogliere le notizie che da essa provengono per comprendere chi è questo essere speciale e particolare. Anche altri filosofi hanno risposto alla "pretesa modernista", però spesso o con un atteggiamento di «falso irenismo», teorizzando un dialogo con cui, prendendo a prestito il metodo illuministico, si è cercato di asserirne "dialetticamente" la falsità, cercando di trattenerne, invece, "le cose buone"; oppure ponendosi come pensatori alternativi al pensiero "comunista" distruttore della «comunità» e della «persona». Secondo MacIntyre, l'errore di questi è nel non aver inteso che la falsità "moderna" è proprio nel suo metodo che ha posto come a-priori non negoziabile, in ogni riflessione e ricerca, il rifiuto della storia, della concretezza, del particolare, della tradizione, propugnando che solo la "spersonalizzazione", la "universalizzazione", insomma: solo il regno della "ragion pura" e auto-purificatasi ha ragione e dignità di essere l'a-priori per eccellenza nella ricerca filosofica. Il «personalismo», nella versione europea, non raramente è incorso in questa confusione.