The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

Out-of-Frame Mutations in ACTN2 Last Exon Cause a Dominant Distal Myopathy With Facial Weakness

Background and Objectives To clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles. Methods Two families with a novel form of actininopathy were identified. Patients had been followed up over 10 years. Their molecular genetic diagnosis was not clear after extensive investigations, including analysis of candidate genes and FSHD1-related D4Z4 repeats. Results Patients shared a similar clinical phenotype and a common pattern of muscle involvement. They presented with a very slowly progressive myopathy involving anterior lower leg and facial muscles. Muscle MRI finding showed complete fat replacement of anterolateral compartment muscles of the lower legs with variable involvement of soleus and gastrocnemius but sparing thigh muscles. Muscle biopsy showed internalized nuclei, myofibrillar disorganization, and rimmed vacuoles. High-throughput sequencing identified in each proband a heterozygous single nucleotide deletion (c.2558del and c.2567del) in the last exon of the ACTN2 gene. The deletions are predicted to lead to a novel but unstructured slightly extended C-terminal amino acid sequence. Discussion Our findings indicate an unusual form of actininopathy with specific molecular and clinical features. Actininopathy should be considered in the differential diagnosis of distal myopathy combined with facial weakness.Peer reviewe

Out-of-Frame Mutations in ACTN2 Last Exon Cause a Dominant Distal Myopathy With Facial Weakness

Background and ObjectivesTo clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles.MethodsTwo families with a novel form of actininopathy were identified. Patients had been followed up over 10 years. Their molecular genetic diagnosis was not clear after extensive investigations, including analysis of candidate genes and FSHD1-related D4Z4 repeats.ResultsPatients shared a similar clinical phenotype and a common pattern of muscle involvement. They presented with a very slowly progressive myopathy involving anterior lower leg and facial muscles. Muscle MRI finding showed complete fat replacement of anterolateral compartment muscles of the lower legs with variable involvement of soleus and gastrocnemius but sparing thigh muscles. Muscle biopsy showed internalized nuclei, myofibrillar disorganization, and rimmed vacuoles. High-throughput sequencing identified in each proband a heterozygous single nucleotide deletion (c.2558del and c.2567del) in the last exon of the ACTN2 gene. The deletions are predicted to lead to a novel but unstructured slightly extended C-terminal amino acid sequence.DiscussionOur findings indicate an unusual form of actininopathy with specific molecular and clinical features. Actininopathy should be considered in the differential diagnosis of distal myopathy combined with facial weakness.</p

From food defence to food supply chain integrity

Purpose – Consumer confidence in the European food industry has been shaken by a number of recent scandals due to food fraud and accidental contamination, reminding the authors that deliberate incidents can occur. Food defence methods aim to prevent or mitigate deliberate attacks on the food supply chain but are not a legal requirement. The purpose of this paper is to discuss how proactive and reactive food defence practices can help prevent or mitigate malicious attacks on the food chain and also food fraud, food crime and food safety. The authors look at how food defence differs from food safety and how it contributes to food supply chain integrity. Design/methodology/approach – Food defence has been the focus of two different EU FP7 security projects, EDEN and SNIFFER. Food industry stakeholders participated in workshops and demonstrations on food defence and relevant technology was tested in different food production scenarios. Findings – Food industry end-users reported a lack of knowledge regarding food defence practices. They wished for further guidelines and training on risk assessment as well as access to validated test methods. Novel detection tools and methods showed promise with authentication, identification, measurement, assessment and control at multiple levels of the food supply chain prior to distribution and retail. Practical implications – The prevention of a contamination incident, prior to retail, costs less than dealing with a large foodborne disease outbreak. Food defence should therefore be integral to food supply chain integrity and not just an afterthought in the wake of an incident. Originality/value – It is argued that food defence practices have a vital role to play across the board in unintentional and intentional food contamination incidents. The application of these methods can help ensure food supply chain integrity.European Union (EU) Seventh Framework Programme projects (FP7/2007-2013): EDEN: End-User Driven Demo for CBRNe, under Grant 61 Food supply chain integrity Downloaded by UNIVERSIDAD DE BURGOS At 07:57 06 January 2017 (PT) Agreement no. 313077, and SNIFFER: Sensory devices network for food supply chain security, under Grant Agreement no. 312411

Planning for Temporally Extended Goals in Pure-Past Linear Temporal Logic

We study classical planning for temporally extended goals expressed in Pure-Past Linear Temporal Logic (PPLTL). PPLTL is as expressive as Linear-time Temporal Logic on finite traces (LTLf), but as shown in this paper, it is computationally much better behaved for planning. Specifically, we show that planning for PPLTL goals can be encoded into classical planning with minimal overhead, introducing only a number of new fluents that is at most linear in the PPLTL goal and no spurious additional actions. Based on these results, we implemented a system called Plan4Past, which can be used along with state-of-the-art classical planners, such as LAMA. An empirical analysis demonstrates the practical effectiveness of Plan4Past, showing that a classical planner generally performs better with our compilation than with other existing compilations for LTLf goals over the considered benchmarks

Age-related changes in conventional, magnetization transfer, and diffusion-tensor MR imaging findings: study with whole-brain tissue histogram analysis.

PURPOSE: To investigate the influence of aging on conventional magnetic resonance (MR) imaging-, magnetization transfer MR imaging-, and diffusion-tensor MR imaging-derived measurements. MATERIALS AND METHODS: Dual-echo T1-weighted magnetization transfer and diffusion-tensor MR images of the brain were obtained in 89 healthy subjects. Normalized brain parenchymal volume (NBV) was measured by using a fully automated technique. Magnetization transfer ratio (MTR), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) histograms were created for the whole brain (MTR values) or for a large representative portion of it (ADC and FA values). Bivariate correlations were assessed by using the Spearman rank correlation coefficient. A stepwise selection procedure was used to identify the combination of variables that were most influenced by subject age in a multivariate regression model. RESULTS: Significant correlations were found between subject age and the following variables: number of hyperintense areas in the brain at T2-weighted MR imaging (r = 0.63, P <.001), NBV (r = -0.79, P <.001), mean ADC (r = 0.34, P =.001), ADC peak height (r = -0.34, P =.001), and FA peak height (r = -0.57, P <.001). NBV correlated significantly with number of hyperintense areas (P <.001), MTR peak height (P <.001), mean ADC (P =.001), ADC peak height (P =.001), and FA peak height (P <.001). The final multivariable regression model included NBV and number of hyperintense areas at T2-weighted MR imaging as independent predictors of subject age. CONCLUSION: In addition to the extent of T2-weighted MR imaging hyperintense areas and the measurement of NBV, diffusion-tensor MR imaging provides additional in vivo information about microstructural age-related brain tissue changes