Fact or fiction: Chronic cerebro-spinal insufficiency

Summary Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Its autoimmune origin has been recently challenged by a substantially different mechanism termed chronic cerebrospinal venous insufficiency (CCSVI), which has attracted worldwide attention in the scientific community, in the media and among MS patients. According to this hypothesis, a congestion of cerebrovenous outflow induces an increased intracranial pressure and a disintegration of the blood–brain barrier in perivenular regions promoting local iron deposition and activation of pro-inflammatory factors, ultimately leading to MS. After the initial report of a perfect association between CCSVI and MS, different independent groups were not able to replicate these results, casting doubts on the credibility of the CCSVI concept in MS. In spite of this, interventional procedures like venous angioplasty named the "liberation" treatment have been claimed as a cure of MS or at least as a major improvement of MS symptoms. As a result, an increasing number of MS patients are undergoing endovascular treatment, in spite of a lack of an evidenced-based benefit and recent reports of serious adverse events. This review represents a critical appraisal of the CCSVI hypothesis, discusses its basis, the diagnostic criteria and its relationship with MS

PulsaR design: CFD comparative study of speed-record Human Powered Vehicles

High speed Human Powered Vehicles (HPVs) are specifically designed in order to race at the World Human Powered Speed Challenge (WHPSC), an event taking place in Nevada, with the purpose of pushing streamlined bike technology to the limits. The poster shows the comparative CFD analysis made during the design process of PulsaR. The prototype was built in the 1st semester of 2015 and raced at the WHPSC in September after about 850 km of testing. Andrea Gallo achieved the Italian Speed Record at 116.19 km/h, becoming the 24th fastest rider in the history of this discipline

Alemtuzumab for multiple sclerosis: the new concept of immunomodulation

Abstract Alemtuzumab (Lemtrada®) is a humanized anti-CD52 IgG1 monoclonal antibody that depletes CD52-expressing cells from the circulation. Robust clinical and radiologic data, derived from clinical trials and long-term observational studies, indicate that alemtuzumab induces a marked immunosuppression related to the depletion of circulating T and B lymphocytes. However, recent advances suggest that the long-term clinical effects of alemtuzumab are probably due to unique qualitative changes in the process of lymphocyte repopulation of the immune system. This leads to a particular rebalancing of the immune system. In this paper we review the immunomodulatory mechanisms underlying the therapeutic effect of alemtuzumab in pre-clinical models and in patients with relapsing remitting multiple sclerosis (RRMS), and stress the importance of a monoclonal antibody-based immunosuppression for treating the severe forms of RRMS. Alemtuzumab has many features of the ideal immunomodulatory drug: rapid biological and clinical actions and and long-lasting benefit. Alemtuzumab can be used as rescue therapy or as first line drug in severe-onset MS. Thus, the availability of alemtuzumab constitutes a significant step forward in the therapy of MS

LÂ’utilizzo degli indicatori compositi nell'analisi congiunturale territoriale: un'applicazione all'economia del Veneto

This paper analyses the business cycle properties of 150 time series, including real and monetary variables, relevant to the regional economy. Following the methodology adopted by Altissimo, Marchetti and Oneto (2000), we propose new monthly coincident and leading composite indicators for the regional business cycle; the leading indicator anticipates the turning points of the coincident indicator on average by five months. With respect to the Italian indicator, recently proposed by ISAE and Bank of Italy, the regional indicator turns out to be particularly sensitive to the evolution of external conditions, revealing cyclical fluctuations not exhibited by the national one. The chronology confirms the peculiarity of the local economy, characterised by a very long expansion lasting from March 1993 to November 1996, tied to the depreciation of the exchange rate as a consequence of the exit from the EMS, and by two idiosyncratic fluctuations. The first one is a short and pronounced cycle occurred during the period 1990-91, coinciding with the Gulf war and the subsequent short recovery driven by the German fiscal expansion tied to the re-unification process. The second is characterised by the relevant recession occurred between February 1998 and April 1999, following the Asian currency and financial crisis.business cycle, coincident and leading indicator, Veneto Region

Effects of herd origin, AI stud and sire identification on genetic evaluation of Holstein Friesian bulls

The purpose of this study was to estimate the effects of herd origin of bull, AI stud and sire identification number (ID) on official estimated breeding values (EBV) for production traits of Holstein Friesian proven bulls. The data included 1,005 Italian Holstein-Friesian bulls, sons of 76 sires, born in 100 herds and progeny tested by 10 AI studs. Bulls were required to have date of first proof between September 1992 and September 1997, to be born in a herd with at least one other bull and to have sire and dam with official EBV when bull was selected for progeny testing. Records of sires with only one son were also discarded. The dependent variable analyzed was the official genetic evaluation for a “quantity and quality of milk” index (ILQ). The linear model to predict breeding values of bulls included the fixed class effects of herd origin of bull, AI testing organization, birth year of bull, and estimated breeding values of sire and dam, both as linear covariates. The R2of the model was 45% and a significant effect was found for genetic merit of sire (P < 0.001) and dam (P < 0.014), for herd origin of bull (P < 0.01) and for birth year of bull (P < 0.001). The effect of AI testing organization was not sig- nificant. The range of herd origin effect was 872 kg of ILQ. However, in this study, the causes of this result were not clear; it may be due to numerous factors, one of which may be preferential treatment on dams of bulls. Analyses of resid- uals on breeding value of proven bulls for ILQ showed a non significant effect of sire ID, after adjusting for parent aver- age, herd origin effect and birth year effect. Although the presence of bias in genetic evaluation of dairy bulls is not evi- dent, further research is recommended firstly to understand the reasons of the significant herd origin effect, secondly to monitor and guarantee the greatest accuracy and reliability of genetic evaluation procedures

Renal impairment and anemia during triple therapy

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Phagocytosis of haemozoin (malarial pigment) enhances metalloproteinase-9 activity in human adherent monocytes: Role of IL-1beta and 15-HETE

<p>Abstract</p> <p>Background</p> <p>It has been shown previously that human monocytes fed with haemozoin (HZ) or trophozoite-parasitized RBCs displayed increased matrix metalloproteinase-9 (MMP-9) enzyme activity and protein/mRNA expression and increased TNF production, and showed higher matrix invasion ability. The present study utilized the same experimental model to analyse the effect of phagocytosis of: HZ, delipidized HZ, beta-haematin (lipid-free synthetic HZ) and trophozoites on production of IL-1beta and MMP-9 activity and expression. The second aim was to find out which component of HZ was responsible for the effects.</p> <p>Methods</p> <p>Native HZ freshly isolated from <it>Plasmodium falciparum </it>(Palo Alto strain, Mycoplasma-free), delipidized HZ, beta-haematin (lipid-free synthetic HZ), trophozoites and control meals such as opsonized non-parasitized RBCs and inert latex particles, were fed to human monocytes. The production of IL-1beta by differently fed monocytes, in presence or absence of specific MMP-9 inhibitor or anti-hIL-1beta antibodies, was quantified in supernatants by ELISA. Expression of IL-1beta was analysed by quantitative real-time RT-PCR. MMP-9 activity and protein expression were quantified by gelatin zymography and Western blotting.</p> <p>Results</p> <p>Monocytes fed with HZ or trophozoite-parasitized RBCs generated increased amounts of IL-1beta and enhanced enzyme activity (in cell supernatants) and protein/mRNA expression (in cell lysates) of monocyte MMP-9. The latter appears to be causally related to enhanced IL-1beta production, as enhancement of both expression and enzyme activity were abrogated by anti-hIL-1beta Abs. Upregulation of IL-1beta and MMP-9 were absent in monocytes fed with beta-haematin or delipidized HZ, indicating a role for HZ-attached or HZ-generated lipid components. 15-HETE (15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid) a potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem-catalysis was identified as one mediator possibly responsible for increase of both IL-1beta production and MMP-9 activity.</p> <p>Conclusion</p> <p>Results indicate that specific lipoperoxide derivatives generated by HZ may play a role in modulating production of IL-1beta and MMP-9 expression and activity in HZ/trophozoite-fed human monocytes. Results may clarify aspects of cerebral malaria pathogenesis, since MMP-9, a metalloproteinase able to disrupt the basal lamina is possibly involved in generation of hallmarks of cerebral malaria, such as blood-brain barrier endothelium dysfunction, localized haemorrhages and extravasation of phagocytic cells and parasitized RBCs into brain tissues.</p