Considerazioni inattuali (?) sulla crisi della storia e della cultura umanistica

Untimely (?) meditations on the crisis of history and humanities.Moving from the debate on the usefulness of history which took place after World War II, this article discusses the present crisis of humanistic culture. At that time Lucien Febvre answered back to the request that history had to be «useful for life» -as Nietzsche said -objecting that «a serving history is a servile history» and that, on the contrary, history is necessary for facing present problems, but only if it is a free construction of a critical method and thinking. Developing Marc Bloch’s thesis on the light of the experiences of the second half of the 20th century, the author confirms the fundamental role of historical consciousness for the formation of democracy and European civilization as well as for their future, being it the only possible antidote against short breath lectures of a present crisis, including the economic one, which is first of all a cultural crisis, and an indispensable tool for thinking and orienting the change

Stochastic Resonance as a tool to optimize Perceptual Learning in neurovisual rehabilitation: An exploratory study

openLa ricerca pilota descritta in questo elaborato mirava ad esplorare il fenomeno controintuitivo del miglioramento percettivo indotto dal rumore nella percezione visiva umana. Questo fenomeno, noto come Risonanza Stocastica, potrebbe risultare particolarmente utile per ottimizzare il Perceptual Learning visivo, su cui si basano diversi protocolli di riabilitazione visiva. L’obiettivo principale di questa ricerca era pertanto la produzione di un’ulteriore evidenza della SR nella percezione visiva umana, e in particolare in un compito utilizzato da un protocollo di riabilitazione visiva chiamato Neural Restoration Therapy. A questo scopo, sono stati condotti tre studi comportamentali con partecipanti normo-vedenti in cui sono stati manipolati i livelli di intensità di rumore visivo casuale, aggiunto agli stimoli visivi, in un compito di discriminazione temporale (2-IFC) di stimoli Gabor Patches. Il primo studio comprendeva 10 condizioni diverse tra loro per intensità di rumore aggiunto agli stimoli, proporzionale al valore di luminanza di ogni pixel dello stimolo. Nel secondo e nel terzo studio il rumore era aggiunto in maniera casuale al 50% dei pixel del riquadro di presentazione degli stimoli, per un totale di 6 condizioni e 5 condizioni, rispettivamente. I risultati dei tre studi hanno mostrato nessun fenomeno di risonanza stocastica. In particolare, nello studio 1 il rumore non aveva alcun effetto sulla prestazione, mentre vi era un effetto della posizione dello stimolo. Nello studio 2 la prestazione era inversamente proporzionale ai livelli di rumore, mentre nello studio 3 non è stato osservato nessun effetto del rumore. Complessivamente, questi risultati suggeriscono che il metodo psicofisico adattivo delle staircase impiegato dal protocollo NRT non porta alla manifestazione della SR. Pertanto, questo fenomeno psicofisico potrebbe non essere utilizzabile nei protocolli riabilitativi visivi basati sul Perceptual Learning.The pilot study described in this paper aimed to explore the counterintuitive phenomenon of perceptual improvement induced by noise in human visual perception. This phenomenon, known as Stochastic Resonance (SR), could prove to be particularly useful for optimizing visual perceptual learning, which forms the basis of various visual rehabilitation protocols. The main objective of this research was to provide further evidence of SR in human visual perception, particularly in a task used by a visual rehabilitation protocol called Neural Restoration Therapy (NRT). To achieve this goal, three behavioral studies were conducted with normally sighted participants in which the levels of random visual noise added to visual stimuli were manipulated in a two-interval forced-choice (2-IFC) task involving Gabor Patches stimuli. The first study included 10 different conditions varying in the intensity of noise added to the stimuli, proportional to the luminance value of each pixel in the stimulus. In the second and third studies, noise was randomly added to 50% of the pixels in the stimulus presentation frame, resulting in a total of 6 and 5 conditions, respectively. The results of the three studies showed no Stochastic Resonance phenomenon. Specifically, in Study 1, noise had no effect on performance, while there was an effect of stimulus location. In Study 2, performance was inversely proportional to noise levels, while in Study 3, no noise effect was observed. Overall, these results suggest that the adaptive psychophysical method used by the NRT protocol, employing staircases, does not lead to the manifestation of SR. Therefore, this psychophysical phenomenon may not be applicable in visual rehabilitation protocols based on Perceptual Learning

Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin

Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease that affects primarily patients older than 60 years. The majority of BP cases are spontaneous, but BP can also be triggered by certain drugs’ exposures. Since 2011, a growing number of observations has been reporting cases of BP in Type 2 diabetic patients. These forms have been linked to the use of a new category of anti-diabetic drugs called dipeptidyl peptidase inhibitors (DPP-4i) or gliptins, but to date, the exact pathophysiological mechanisms underlying this association are not completely elucidated. Although conventional and gliptin-associated BP are thought to share similar clinical and histopathological features, our thorough review of the most recent literature, shows that these 2 forms are quite distinct: DPP-4-i-associated BP seems to appear at an earlier age than spontaneous BP, it may manifest either as a noninflammatory or inflammatory phenotype, while the conventional form presents with a typical inflammatory phenotype. Additionally, an important distinctive histological feature was recently shown in Gliptin-associated BP: these forms may present a less significant eosinophils infiltrate in the upper dermis of peri-blister lesions compared to the skin of patients with spontaneous BP, and this seems a specific feature of the clinically non-inflammatory forms. In accordance with previous literature, we found that the direct immunofluorescence (DIF) gives identical findings in both DPP-4i-associated and conventional forms of BP which is an IgG and complement C3 deposition as a linear band at the dermal–epidermal junction in perilesional skin. Indirect immunofluorescence shows the presence of IgG circulating autoantibodies in the patient's serum which titer does not differ between spontaneous and DPP-4i-associated BP, while the specificity of these autoantibodies, may be different in spontaneous, induced non-inflammatory and induced inflammatory forms, epitope spreading phenomenon seems to play a role in determining these specificities. Further research, based on integrated epidemiological, clinical, histo-immunological and pharmacogenomic approaches, may give more insight into these forms of BP. This combined approach will allow to better define BP endotypes and to unveil the mechanism of spontaneous or drug-induced breakage of the immunotolerance to skin self-antigens

Measuring Hospital Performance Using Mortality Rates: An Alternative to the RAMR

Background The risk-adjusted mortality rate (RAMR) is used widely by healthcare agencies to evaluate hospital performance. The RAMR is insensitive to case volume and requires a confidence interval for proper interpretation, which results in a hypothesis testing framework. Unfamiliarity with hypothesis testing can lead to erroneous interpretations by the public and other stakeholders. We argue that screening, rather than hypothesis testing, is more defensible. We propose an alternative to the RAMR that is based on sound statistical methodology, easier to understand and can be used in large-scale screening with no additional data requirements. Methods We use an upper-tail probability to screen for hospitals performing poorly and a lower-tail probability to screen for hospitals performing well. Confidence intervals and hypothesis tests are not needed to compute or interpret our measures. Moreover, unlike the RAMR, our measures are sensitive to the number of cases treated. Results To demonstrate our proposed methodology, we obtained data from the New York State Department of Health for 10 Inpatient Quality Indicators (IQIs) for the years 2009-2013. We find strong agreement between the upper tail probability (UTP) and the RAMR, supporting our contention that the UTP is a viable alternative to the RAMR. Conclusion We show that our method is simpler to implement than the RAMR and, with no need for a confidence interval, it is easier to interpret. Moreover, it will be available for all hospitals and all diseases/conditions regardless of patient volum

The pathogenesis of Charcot neuroarthropathy: current concepts

The pathogenesis of Charcot neuroarthropathy (CN) has been poorly understood by clinicians and scientists alike. Current researchers have made progress toward understanding the cause of CN and possible treatment options. The authors review the current literature on the pathogenesis of this debilitating disorder and attempt to explain the roles of inflammation, bone metabolism, and advanced glycation end products

Toxicity of Bothrops jararacussu (jararacuçu) snake venom and bothropstoxin in rat isolated right atria

Orientador: Stephen HyslopDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Serpentes do gênero Bothrops são a principal causa de acidentes ofídicos no Brasil. Acidentes envolvendo a Bothrops jararacussu (jararacuçu) resultam em envenenamento moderado e grave, devido principalmente à grande quantidade de peçonha injetada por esta espécie. Entre os efeitos observados, o quadro de hipotensão e de choque são fatores importantes a serem considerados. Neste trabalho, avaliamos as alterações cardíacas causadas pela peçonha de B. jararacussu em átrio direito isolado de rato. A incubação das preparações com peçonha (0,025, 0,050, 0,1 e 0,2 mg/ml) resultou em uma marcada contratura atrial em altas concentrações que levou a uma redução progressiva da força contrátil e a freqüência atrial, especialmente na maior concentração utilizada (0,2 mg/ml). A maior concentração da peçonha também causou uma marcada liberação de CK-BM e desorganização das fibras musculares atriais. A peçonha aquecida (100°C, 20 min) aboliu esta atividade enquanto a diálise não alterou significativamente essas respostas. O fracionamento da peçonha de B. jararacussu em cromatografia por gel filtração e troca iônica nos forneceu a fração (III3) que reproduziu todas as alterações funcionais e morfológicas vistas com a peçonha bruta. SDS-PAGE da fração III3, na presença e ausência de ditiotreitol e ß-mecaptoetanol revelaram uma massa molecular de ~28 KDa e 14 KDa, respectivamente, semelhantes às bothropstoxinas, as principais PLA2 miotóxicas desta peçonha. Os antivenenos comerciais utilizados (botrópico e botrópico/crotálico) se mostraram eficientes em neutralizar os efeitos produzidos pela peçonha bruta tanto na força e freqüência atriais como na liberação de CK-MB e nas alterações histológicas. A pré-incubação com antagonistas farmacológicos (bloqueadores de receptores adrenérgicos, histaminérgicos, muscarínicos, e inibidores da ciclooxigenase e óxido nítrico sintase) não afetou significativamente as alterações induzidas pela peçonha. Estes resultados indicam que as alterações induzidas pela peçonha de B. jararacussu estão envolvidas diretamente com o dano a fibra muscular atrial mediada provavelmente através da atividade das PLA2 miotóxicas.Abstract: The genus Bothrops is the principal cause of snakebite in Brazil. Bites by Bothrops jararacussu (jararacuçu) result in moderate to severe envenoming partly because of the large amount of venom injected by this species. Hypotension and circulatory shock are important systemic manifestations associated with bites by this species. In this work, we examined the cardiac alterations caused by B. jararacussu venom in rat isolated right atria. Incubation of atria with venom (0.025, 0.050, 0.1 and 0.2 mg/ml) resulted in marked muscle contracture at high concentrations that led to a progressive decrease in contractile force and beating rate, especially at the highest concentration (0.2 mg/ml). The highest venom concentrations also caused a marked release of CK-MB and disorganization of atrial muscle fibers. Heating the venom (100ºC, 20 min) abolished this activity whereas dialysis did not significantly alter the responses. Fractionation of B. jararacussu venom by gel filtration and ion exchange chromatographies yielded a peak (III-3) that reproduced all of the morphological and functional changes seen with the venom. SDS-PAGE of the peak III-3 protein in the absence and presence - mercaptoethanol revealed a molecular mass of ~28 KDa and 14 KDa, respectively, similar to bothropstoxins, the main myotoxic PLA2 of this venom. Bothropic and bothropic/crotalic antivenoms prevented the venom (0.2 mg/ml)-induced decrease in contractile force and atrial rate, as well as the tissue damage (CK-MB release and histological alterations). Pre-incubation with adrenergic, histaminergic and muscarinic receptor antagonists, or with cyclooxygenase and nitric oxide synthase inhibitors, did not significantly affect the venom-induced changes. These results indicate that the B. jararacussu venom-induced alterations probably involve direct to atrial muscle fibers mediated by venom myotoxic PLA2.MestradoMestre em Farmacologi

Measuring Hospital Performance Using Mortality Rates: An Alternative to the RAMR

Abstract Background: The risk-adjusted mortality rate (RAMR) is used widely by healthcare agencies to evaluate hospital performance. The RAMR is insensitive to case volume and requires a confidence interval for proper interpretation, which results in a hypothesis testing framework. Unfamiliarity with hypothesis testing can lead to erroneous interpretations by the public and other stakeholders. We argue that screening, rather than hypothesis testing, is more defensible. We propose an alternative to the RAMR that is based on sound statistical methodology, easier to understand and can be used in large-scale screening with no additional data requirements. Methods: We use an upper-tail probability to screen for hospitals performing poorly and a lower-tail probability to screen for hospitals performing well. Confidence intervals and hypothesis tests are not needed to compute or interpret our measures. Moreover, unlike the RAMR, our measures are sensitive to the number of cases treated. Results: To demonstrate our proposed methodology, we obtained data from the New York State Department of Health for 10 Inpatient Quality Indicators (IQIs) for the years 2009-2013. We find strong agreement between the upper tail probability (UTP) and the RAMR, supporting our contention that the UTP is a viable alternative to the RAMR. Conclusion: We show that our method is simpler to implement than the RAMR and, with no need for a confidence interval, it is easier to interpret. Moreover, it will be available for all hospitals and all diseases/conditions regardless of patient volume

A System of ODEs for Representing Trends of CGM Signals

Diabetes Mellitus is a metabolic disorder which may result in severe and potentially fatal complications if not well-treated and monitored. In this study, a quantitative analysis of the data collected using CGM (Continuous Glucose Monitoring) devices from eight subjects with type 2 diabetes in good metabolic control at the University Polyclinic Agostino Gemelli, Catholic University of the Sacred Heart, was carried out. In particular, a system of ordinary differential equations whose state variables are affected by a sequence of stochastic perturbations was proposed and used to extract more informative inferences from the patients' data. For this work, Matlab and R programs were used to find the most appropriate values of the parameters (according to the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC)) for each patient. Fitting was carried out by Particle Swarm Optimization to minimize the ordinary least squares error between the observed CGM data and the data from the ODE model. Goodness of fit tests were made in order to assess which probability distribution was best suitable for representing the waiting times computed from the model parameters. Finally, both parametric and non-parametric density estimation of the frequency histograms associated with the variability of the glucose elimination rate from blood were conducted and their representative parameters assessed from the data. The results show that the chosen models succeed in capturing most of the glucose fluctuations for almost every patient