RISPOSTA TERAPEUTICA A TETRAIDROCANNABINOLO/CANNABIDIOLO NELLA SPASTICITA' ASSOCIATA A SCLEROSI MULTIPLA

Sativex® è un spray oromucosale atto alla terapia della spasticità in corso di sclerosi multipla. Esso contiene due principi attivi, il Δ9-tetraidrocannabinolo (THC) e il cannabidiolo (CBD), entrambi derivati dalla pianta di Cannabis Sativa, i quali agiscono modulando il sistema endocannabinoide umano. L'obiettivo della nostra analisi retrospettiva è stato quello di valutare la risposta terapeutica a tale farmaco in 35 pazienti, che non avevano precedentemente risposto ad altri trattamenti antispastici. Per tale valutazione, ci siamo avvalsi di 4 parametri (NRS per la spasticità, EDSS, Ambulation Index, test dei 10 metri), valutati prima e dopo un periodo di terapia di 4 settimane. Tale analisi ha mostrato efficacia nel ridurre l'NRS per la spasticità (riduzione del 26,6% nei responders), ma scarsa efficacia sugli altri paramentri. Il farmaco ha inoltre dimostrato una discreta efficacia sul dolore associato alla spasticità. Inoltre, valutando la terapia nel lungo termine, si è notato che tale trattamento mantiene la sua efficacia anche dopo molti cicli di terapia. Sativex® is a oromucosal spray for the treatment of spasticity in course of multiple sclerosis. It contains Δ9 - tetrahydrocannabinol (THC) and cannabidiol (CBD) , both derived from the plant "Cannabis sativa". The aim of our retrospective analysis was to evaluate the therapeutic response to Sativex® in 35 patients , who had not previously responded to other antispasticity agents .For this evaluation , we used four parameters ( NRS for spasticity , EDSS , Ambulation Index, tests of 10 meters ) , checked before and after a treatment period of 4 weeks .This analysis has shown effectiveness in reducing NRS for spasticity (26.6% reduction in responders) , but little effect on other parameters . The drug also showed a fairly effective on pain, associated with spasticity. Moreover , considering the long-term therapy , it has been noted that such treatment remains effective

The quality of student dialogue in citizenship education

This study investigates the relationship between the quality of student dialogue and students’ ability to justify their viewpoints on a moral issue. A curriculum unit for dialogic citizenship education was developed and implemented in the 8th grade of secondary education. In the final lesson, students discussed a moral issue and then wrote an essay on it. The results show that students who made more value-related utterances during the discussion also referred more often and more explicitly in their individually written essays to moral values. This study indicates that the quality of the content of students’ dialogue is important for their ability to substantiate their opinion on moral issues with value-laden argumentation. Approaches to citizenship education in which dialogue is a central element should, therefore, pay specific attention to the validation of ideas in student dialogue

A proportion of mutations fixed in the genomes of in vitro selected isogenic drug-resistant Mycobacterium tuberculosis mutants can be detected as minority variants in the parent culture.

We studied genomic variation in a previously selected collection of isogenic Mycobacterium tuberculosis laboratory strains subjected to one or two rounds of antibiotic selection. Whole genome sequencing analysis identified eleven single, unique mutations (four synonymous, six non-synonymous, one intergenic), in addition to drug resistance-conferring mutations, that were fixed in the genomes of six monoresistant strains. Eight loci, present as minority variants (five non-synonymous, three synonymous) in the genome of the susceptible parent strain, became fixed in the genomes of multiple daughter strains. None of these mutations are known to be involved with drug resistance. Our results confirm previously observed genomic stability for M. tuberculosis, although the parent strain had accumulated allelic variants at multiple locations in an antibiotic-free in vitro environment. It is therefore likely to assume that these so-called hitchhiking mutations were co-selected and fixed in multiple daughter strains during antibiotic selection. The presence of multiple allelic variations, accumulated under non-selective conditions, which become fixed during subsequent selective steps, deserves attention. The wider availability of 'deep' sequencing methods could help to detect multiple bacterial (sub)populations within patients with high resolution and would therefore be useful in assisting in the detailed investigation of transmission chains

Overcoming the barriers to implementing urban road user charging schemes

Urban road user charging offers the potential to achieve significant improvements in urban transport, but is notoriously difficult to implement. Cities need guidance on the range of factors to be considered in planning and implementing such schemes. This paper summarises the results of a 3 year programme which has collated evidence on the issues of most concern to cities. A state of the art report has provided evidence on 14 themes, ranging from objectives and design to implementation and evaluation. A set of 16 case studies has reviewed experience in design and implementation across Europe. The paper summarises their findings, provides references to more detailed information, presents the resulting policy recommendations to European, national and local government, and outlines the areas in which further research is needed

Pyrazinamide resistance-conferring mutations in pncA and the transmission of multidrug resistant TB in Georgia.

BACKGROUND: The ongoing epidemic of multidrug-resistant tuberculosis (MDR-TB) in Georgia highlights the need for more effective control strategies. A new regimen to treat MDR-TB that includes pyrazinamide (PZA) is currently being evaluated and PZA resistance status will largely influence the success of current and future treatment strategies. PZA susceptibility testing was not routinely performed at the National Reference Laboratory (NRL) in Tbilisi between 2010 and September 2015. We here provide a first insight into the prevalence of PZA resistant TB in this region. METHODS: Phenotypic susceptibility to PZA was determined in a convenience collection of well-characterised TB patient isolates collected at the NRL in Tbilisi between 2012 and 2013. In addition, the pncA gene was sequenced and whole genome sequencing was performed on two isolates. RESULTS: Out of 57 isolates tested 33 (57.9%) showed phenotypic drug resistance to PZA and had a single pncA mutation. All of these 33 isolates were MDR-TB strains. pncA mutations were absent in all but one of the 24 PZA susceptible isolate. In total we found 18 polymorphisms in the pncA gene. From the two major MDR-TB clusters represented (94-32 and 100-32), 10 of 15, 67.0% and 13 of 14, 93.0% strains, respectively were PZA resistant. We also identified a member of the potentially highly transmissive clade A strain carrying the characteristic I6L substitution in PncA. Another strain with the same MLVA type as the clade A strain acquired a different mutation in pncA and was genetically more distantly related suggesting that different branches of this particular lineage have been introduced into this region. CONCLUSION: In this high MDR-TB setting more than half of the tested MDR-TB isolates were resistant to PZA. As PZA is part of current and planned MDR-TB treatment regimens this is alarming and deserves the attention of health authorities. Based on our typing and sequence analysis results we conclude that PZA resistance is the result of primary transmission as well as acquisition within the patient and recommend prospective genotyping and PZA resistance testing in high MDR-TB settings. This is of utmost importance in order to preserve bacterial susceptibility to PZA to help protect (new) second line drugs in PZA containing regimens

ESPEN Guidelines on Enteral Nutrition: Wasting in HIV and other chronic infectious diseases

Summary Undernutrition (wasting) is still frequent in patients infected with the human immunodeficiency virus (HIV), despite recent decreases in the prevalence of undernutrition in western countries (as opposed to developing countries) due to the use of highly active antiretroviral treatment. Undernutrition has been shown to have a negative prognostic effect independently of immunodeficiency and viral load. These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) in HIV-infected patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. Nutritional therapy is indicated when significant weight loss (45% in 3 months) or a significant loss of body cell mass (45% in 3 months) has occurred, and should be ARTICLE IN PRES

Australians’ views on carbon pricing before and after the 2013 federal election

As climate policies change through the legislative process, public attitudes towards them may change as well. Therefore, it is important to assess how people accept and support controversial climate policies as the policies change over time. Policy acceptance is a positive evaluation of, or attitude towards, an existing policy; policy support adds an active behavioural component1, 3. Acceptance does not necessarily lead to support. We conducted a national survey of Australian residents to investigate acceptance of, and support for, the Australian carbon pricing policy before and after the 2013 federal election, and how perceptions of the policy, economic ideology, and voting behaviour affect acceptance and support. We found acceptance and support were stable across the election period, which was surprising given that climate policy was highly contentious during the election. Policy acceptance was higher than policy support at both times and acceptance was a necessary but insufficient condition of support. We conclude that acceptance is an important process through which perceptions of the policy and economic ideology influence support. Therefore, future climate policy research needs to distinguish between acceptance and support to better understand this process, and to better measure these concepts