PARK20 caused by SYNJ1 homozygous Arg258Gln mutation in a new Italian family

SYNJ1 has been recently identified by two independent groups as the gene defective in a novel form of autosomal recessive, early-onset atypical parkinsonism (PARK20). Two consanguineous families were initially reported (one of Sicilian and one of Iranian origins), with the same SYNJ1 homozygous mutation (c.773G > A, p.Arg258Gln) segregating with a similar phenotype of early-onset parkinsonism and additional atypical features. Here, we report the identification of the same SYNJ1 homozygous mutation in two affected siblings of a third pedigree. Both siblings had mild developmental psychomotor delay, followed, during the third decade of life, by progressive parkinsonism, dystonia, and mild cognitive impairment. One sibling suffered one episode of generalized seizures. Neuroimaging studies revealed severe nigrostriatal dopaminergic defects, mild striatal and very mild cortical hypometabolism. Treatment with dopamine agonists and anticholinergics resulted in partial improvements. Genetic analyses revealed in both siblings the SYNJ1 homozygous c.773G > A (p.Arg258Gln) mutation. Haplotype analysis suggests that the mutation has arisen independently in this family and the Sicilian PARK20 family previously described by us, in keeping with the hypothesis of a mutational hot spot. This is the third reported family with autosomal recessive, early-onset parkinsonism associated with the SYNJ1 p.Arg258Gln mutation. This work contributes to the definition of the genetic and clinical aspects of PARK20. This newly recognized form must be considered in the diagnostic work-up of patients with early-onset atypical parkinsonism. The presence of seizures might represent a red flag to suspect PARK20.

Sliding windows over uncertain data streams

Uncertain data streams can have tuples with both value and existential uncertainty. A tuple has value uncertainty when it can assume multiple possible values. A tuple is existentially uncertain when the sum of the probabilities of its possible values is $$<$$<1. A situation where existential uncertainty can arise is when applying relational operators to streams with value uncertainty. Several prior works have focused on querying and mining data streams with both value and existential uncertainty. However, none of them have studied, in depth, the implications of existential uncertainty on sliding window processing, even though it naturally arises when processing uncertain data. In this work, we study the challenges arising from existential uncertainty, more specifically the management of count-based sliding windows, which are a basic building block of stream processing applications. We extend the semantics of sliding window to define the novel concept of uncertain sliding windows and provide both exact and approximate algorithms for managing windows under existential uncertainty. We also show how current state-of-the-art techniques for answering similarity join queries can be easily adapted to be used with uncertain sliding windows. We evaluate our proposed techniques under a variety of configurations using real data. The results show that the algorithms used to maintain uncertain sliding windows can efficiently operate while providing a high-quality approximation in query answering. In addition, we show that sort-based similarity join algorithms can perform better than index-based techniques (on 17 real datasets) when the number of possible values per tuple is low, as in many real-world applications. © 2014, Springer-Verlag London

Low-grade periprosthetic knee infection: diagnosis and management

Diagnosis and management of low-grade periprosthetic knee infection are still controversial and debatable. The diagnosis of low-grade infection after total knee arthroplasty is often complex, as clinical symptomatology and diagnostic studies are highly conflicting and knees often exhibit well-fixed components. Although the criterion standard for staged reimplantation is interim placement of an antibiotic-loaded spacer, less-invasive surgical procedures have been advocated for managing infections caused by low-virulence bacteria. Debridement with polyethylene exchange and single-stage reimplantation could offer advantages, such as fewer surgeries, reduced potential for intraoperative complications, and lower direct social costs. The aim of this narrative review was to analyze the literature to evaluate the effectiveness of different surgical procedures in managing low-grade periprosthetic knee infections. Additionally, the most reliable investigations for diagnosing total knee infection caused by low-virulence bacteria were reviewed.

In-Depth Oral Presentations and Oral Communications

Vertebral body compression fracture after percutaneous pedicle screw removal in a young man

Hazards and potential complications associated with pedicle screw insertions have been reported. In contrast, complications due to implant removal are rarely described. An unreported case of acute vertebral body compression fracture following pedicle screw removal in a young man occurred during an episode of forceful coughing. Spinal implants need to be removed in cases of complications, pain or tissue irritation, and removal is mandatory when fixation involves L2 or the lower segments. Complications associated with spinal implant removal are rare but possible, and patients must be informed of this potential risk.

Photodynamic Therapy with 5-Aminolevulinic Acid InducesApoptosis and Caspase Activation in Malignant T Cells

Background: Preliminary studies have suggested that photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) can improve psoriasis and mycosis fungoides, two diseases where normal or malignant T cells play a central role. Objectives: To determine if ALA-PDT induces apoptosis and caspase activation in Jurkat cells, a malignant T-cell line. Methods: Jurkat cells were incubated with ALA in the presence of [14C]-thymidine followed by red light exposure. DNA fragmentation was measured 24 hours later with a DNA elution assay. The influence on DNA fragmentation of ALA concentration, time between ALA addition and light exposure, as well as light fluence were studied. The occurrence of oligonucleosome-sized DNA fragmentation was also studied with DNA electrophoresis. Caspase-3-like activity was monitored by measuring Ac-DEVD-AMC hydrolysis. Results: DNA fragmentation as high as 88% was observed 24 hours after ALA-PDT. The percentage of DNA fragmentation increased with increasing doses of ALA, red light fluence, as well as longer incubation time with ALA. DNA fragmentation was observed as early as 3 hours after ALA-PDT. The presence of apoptosis after ALA-PDT was confirmed by DNA electrophoresis. An increase in caspase-3-like activities was detected following ALA-PDT. Conclusion: ALA-PDT induces apoptosis and caspase-3-like activation in Jurkat cells.

Computational modelling of emboli travel trajectories in cerebral arteries: influence of microembolic particle size and density

Ischaemic stroke is responsible for up to 80% of stroke cases. Prevention of the reoccurrence of ischaemic attack or stroke for patients who survived the first symptoms is the major treatment target. Accurate diagnosis of the emboli source for a specific infarction lesion is very important for a better treatment for the patient. However, due to the complex blood flow patterns in the cerebral arterial network, little is known so far of the embolic particle flow trajectory and its behaviour in such a complex flow field. The present study aims to study the trajectories of embolic particles released from carotid arteries and basilar artery in a cerebral arterial network and the influence of particle size, mass and release location to the particle distributions, by computational modelling. The cerebral arterial network model, which includes major arteries in the circle of Willis and several generations of branches from them, was generated from MRI images. Particles with diameters of 200, 500 and 800 μm and densities of 800, 1,030 and 1,300 kg/m(3) were released in the vessel's central and near-wall regions. A fully coupled scheme of particle and blood flow in a computational fluid dynamics software ANASYS CFX 13 was used in the simulations. The results show that heavy particles (density large than blood or a diameter larger than 500 μm) normally have small travel speeds in arteries; larger or lighter embolic particles are more likely to travel to large branches in cerebral arteries. In certain cases, all large particles go to the middle cerebral arteries; large particles with higher travel speeds in large arteries are likely to travel at more complex and tortuous trajectories; emboli raised from the basilar artery will only exit the model from branches of basilar artery and posterior cerebral arteries. A modified Circle of Willis configuration can have significant influence on particle distributions. The local branch patterns of internal carotid artery to middle cerebral artery and anterior communicating artery can have large impact on such distributions.

Training and wages of older workers in Europe

The financial deficits of many social security systems caused by ageing populations and stagnating economies are forcing workers to retire later from the labour market. An extended working life, combined with rapid technological progress in many sectors, is likely making older workers' skills obtained in school obsolete. In this context, lifelong investment in training is widely recognised among the international research and policy community as a key element to increase or at least limit the decline in productivity of older workers. This paper investigates the relationship between training undertaken by European older workers and their wages, relying on the Survey of Health, Ageing and Retirement in Europe. There is no evidence of training wage premium for older workers residing in many European countries including Denmark, Sweden, Belgium, the Netherlands, and Switzerland. Very high premiums are instead found for Austria, Germany, Greece and Italy. It is, however, likely that these high premiums are overestimated due to training endogeneity and sample selection bias.

Measuring Adherence by Visual Inspection of Returned Empty Gel Applicators in the CAPRISA 004 Microbicide Trial

In the CAPRISA 004 trial, adherence was estimated as the proportion of reported sex acts covered by two gel doses, which was assessed by counting returned empty gel applicators. The returned empty applicators were inspected visually in a standardized manner for residue on the outside of the applicator, as an indicator of vaginal insertion. Over 15 months, spanning 11,839 study visits by 838 women, a total of 59,800 returned empty applicators were inspected. By visual assessment, 77.5 % of these applicators appeared to have been inserted. To test the accuracy of the assessment we fitted a Cox model and found that the risk for HIV infection was doubled when less than half of the returned empty applicators had been assessed as not inserted in the vagina. Visual inspection enhanced both the accuracy of the adherence measurement and aided identification of mechanical problems with applicator use experienced by women in the trial.

Monitoring Microbicide Gel Use with Real-Time Notification of the Container’s Opening Events: Results of the CAPRISA Wisebag Study

Accurate estimation of the effectiveness of a microbicide for HIV prevention requires valid measurement of adherence to product use. A microbicide gel applicator container (Wisebag), fitted with cell phone technology to transmit opening events and text message reminders, was developed to monitor each opening event of the container as a proxy for gel use and adherence. Ten women were enrolled in a pilot study and followed for up to 4 months. Wisebag opening (WBO) dates and times were recorded and correlated with self-reported sex acts and gel applicator returns. During the 33 monthly follow-up visits, 47.8 % (77/161) of the recorded number of WBO events were concordant with the number of empty (used) applicators returned. The discrepancies were likely due to removal of more than one applicator during a single opening event. When the date and time of the WBO event data was assessed in relation to three different self-report adherence measures, agreement was fairly modest. The Wisebag was found to be acceptable as a storage container and the cell phone reminders generated were useful in supporting the dosing strategy. We recommend that the Wisebag be considered for larger scale and lengthier testing in microbicide trials.