This review summarizes recent advances in the area of tribology based on the outcome of a Lorentz Center workshop surveying various physical, chemical and mechanical phenomena across scales. Among ...the main themes discussed were those of rough surface representations, the breakdown of continuum theories at the nano- and microscales, as well as multiscale and multiphysics aspects for analytical and computational models relevant to applications spanning a variety of sectors, from automotive to biotribology and nanotechnology. Significant effort is still required to account for complementary nonlinear effects of plasticity, adhesion, friction, wear, lubrication and surface chemistry in tribological models. For each topic, we propose some research directions.
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•Rasmussen Encephalitis has an autoimmune pathogenesis, but the only definitive treatment is functional hemispherectomy•Agents interfering with the immune system are used to treat patients with a ...slow progression or not eligible for surgery•There is no sufficient evidence to support a specific immunosuppressive agent for RE, as the clinical experience is limited•Knowledge progress on RE pathogenesis, featuring a T CD8 cell response, has optimized the use of immunosuppressive agents•The use of T-targeted treatments represents a promising alternative for the treatment of patients suffering from RE
Rasmussen encephalitis (RE) is a unilateral hemispheric encephalitis whose main clinical features include refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Despite the autoimmune pathogenesis of RE, the only definitive therapeutic option is currently represented by surgery.
We review the clinical features, the immune pathogenesis, and the available therapeutic options for RE, with special focus on immunosuppressive agents. The research includes systematic reviews, meta-analyses, observational studies, clinical trials, cases series and reports, until 2020.
The use of immunosuppressive agents in RE is supported by the evidence of an autoimmune involvement of the central nervous system in this condition. Although often insufficient to modify the disease course and to achieve symptomatic control, immune therapy can be effective in patients with slow disease progression or in patients in which surgery is not applicable. Moreover, the documentation of T-cell involvement in the pathogenesis of RE, with a specific cytokine pattern, opens a window of opportunity for the use of T-targeted therapies and biologic drugs (i.e. anti-TNFα agents) in the treatment of this disease.
Summary
22q11.2 deletion syndrome (22q11.2DS) is characterized by a heterogeneous phenotype, including alterations in phospho‐calcium metabolism and immunodeficiency. We analyzed vitamin D status and ...the immune assessment, focusing on T cell subpopulations and dendritic cells (DCs) in a cohort of 17 pediatric 22q11.2DS patients and 17 age‐matched healthy subjects. As antigen‐presenting cells, DCs are the main target of vitamin D, promoting a tolerogenic T cell response. Patients were subdivided into three groups according to the parameters of phospho‐calcium metabolism and serum levels of 25OHD: normal values, vitamin D deficiency and hypoparathyroidism. Different degrees of T cell deficiency, ranging from normal to partial T cell numbers, were observed in the cohort of patients. The group with vitamin D deficiency showed a significant reduction of naive T cells and a significant increase of central memory T cells compared to controls. In this group the number of circulating DCs was significantly reduced. DC decrease affected both myeloid and plasmacytoid DC subsets (mDCs and pDCs), with the most relevant reduction involving pDCs. A direct correlation between 25OHD levels and recent thymic emigrant (RTE) and DC number was identified. Despite the limited cohort analyzed, our results show that deficiency of the pDC subset in patients with 22q11.2DS may be included among the causative factors of the progressive increase of risk of autoimmune diseases in these patients. As most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, we suggest a potential role of vitamin D supplementation in preventing autoimmune or proinflammatory diseases in 22q11.2DS.
This study analyzes vitamin D status and the immune assessment in patients with 22q11.2 deletion syndrome (22q11.2DS), with the main focus on dendritic cells (DCs). Patients with vitamin D deficiency show a significant reduction of DCs number, with the most relevant decrease observed in plasmacytoid DCs (pDCs). As most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, we suggest that the pDC defect could be contributing to the progressive risk of autoimmune diseases in patients with 22q11.2DS. A potential role of vitamin D supplementation in preventing autoimmune or pro‐inflammatory diseases in these patients is discussed.
Status epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged ...seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam. IL-1β signal blockade with Anakinra has shown promising results in avoiding seizure recurrence and generalization in inflammatory refractory epilepsy. Inhibiting the IL-1β converting enzyme (ICE)/caspase-1 is also being investigated as a possible target for managing drug-resistant epilepsies. Targeting the ATP-P2X7R signal, which activates the NLRP3 inflammasome and triggers inflammatory molecule release, is another avenue of research. Interestingly, astaxanthin has shown promise in attenuating neuroinflammation in SE by inhibiting the ATP-P2X7R signal. Furthermore, IL-6 blockade using tocilizumab has been effective in RSE and in reducing seizures in patients with febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include the ketogenic diet, which may modulate pro-inflammatory cytokine production, and the use of cannabidiol (CBD), which has demonstrated antiepileptic, neuroprotective, and anti-inflammatory properties, and targeting HMGB1-TLR4 axis. Clinical experience with anti-cytokine agents such as Anakinra and Tocilizumab in SE is currently limited, although promising. Nonetheless, Etanercept and Rituximab have shown efficacy only in specific etiologies of SE, such as autoimmune encephalitis. Overall, targeting inflammatory pathways and cytokines shows potential as an innovative therapeutic option for drug-resistant epilepsies and SE, providing the chance of directly addressing its underlying mechanisms, rather than solely focusing on symptom control.
Purpose
46, XY disorders (or differences) of sex development (DSD) are a group of clinical conditions with variable genetic background; correct diagnosis is often difficult, but it permits to ...optimize the management. The aim of this study is to identify clinical and genetics features of a group of women with 46, XY DSD to define some issues characterizing people with 46, XY DSD in Italy.
Methods
Retrospective analysis of girls and women with 46, XY DSD and female phenotype evaluated between year 2000 and 2016, performed by anonymised database, focusing on the clinical features and management, including presentation, first diagnostic suspect, gonadal surgery and molecular diagnostic delay.
Results
A total of 84 records were collected (mean age at clinical presentation: 9.1 ± 7.9 years; mean age at definitive diagnosis: 20.1 ± 15.0 years). Complete androgen insensitivity syndrome was the most common diagnosis (60%). Only 12 patients (14.3%) did not receive a molecular diagnosis. Early misdiagnoses frequently occurred; diagnostic delay was 10.2 ± 11.2 years, being reduced in patients presenting from 2007 to 2016. The discordance between genotypic and phenotypic sex during pregnancy or at birth determined early reason for referral in a considerable percentage (4.9%).
Conclusion
Misdiagnosis and long diagnostic delays are present in females with 46, XY DSD in Italy, but the new genetic techniques permit faster right diagnoses in the last years. The centralization in dedicated third level units permits to reduce the number of patients without a molecular diagnosis, allowing better clinical management and appropriate genetic counselling.
In this paper, we present an FP-like approach, named class point, which was conceived to estimate the size of object-oriented products. In particular, two measures are proposed, which are ...theoretically validated showing that they satisfy well-known properties necessary for size measures. An initial, empirical validation is also performed, meant to assess the usefulness and effectiveness of the proposed measures to predict the development effort of object-oriented systems. Moreover, a comparative analysis is carried out, taking into account several other size measures.
Terminal deletions of long arm of chromosome 13 are rare and poorly characterized by cytogenetic studies, making for difficult genotype-phenotype correlations. We report two siblings presenting ...generalized epilepsy, intellectual disability, and genitourinary tract defects. Array CGH detected a 1.3 Mb deletion at 13q34; it contains two protein-coding genes, SOX1 and ARHGEF7, whose haploinsufficiency can contribute to the epileptic phenotype.
Rasmussen syndrome (RS) is a chronic encephalopathy with uncertain etiology and immune-mediated pathogenesis. The only definitive treatment is represented by functional hemispherectomy. We describe ...the case of a 6.5-year-old female patient who developed several episodes of focal, unilateral clonic seizures. Following laboratory and instrumental investigations, the patient was diagnosed as having RS. A treatment with corticosteroids, intravenous immunoglobulin, and the antiseizure medication (carbamazepine and levetiracetam) did not completely control the seizures. Therefore, the patient was treated with mycophenolate mofetil (MMF), showing a good clinical response, with reduction of the seizures, and stability of the radiological findings. This case suggests the potential utility of MMF in the immune approach to RS.
•Rasmussen encephalitis (RE) is an immune-mediated disease of unknown etiology.•Current definitive treatment for RE is represented by hemispherectomy.•The immune approach of RE has been performed with several agents.•In this case, mycophenolate mofetil was successfully used in a patient with RE.
Monitoring Online Tests through Data Visualization Costagliola, G.; Fuccella, V.; Giordano, M. ...
IEEE transactions on knowledge and data engineering,
06/2009, Letnik:
21, Številka:
6
Journal Article
Recenzirano
We present an approach and a system to let tutors monitor several important aspects related to online tests, such as learner behavior and test quality. The approach includes the logging of important ...data related to learner interaction with the system during the execution of online tests and exploits data visualization to highlight information useful to let tutors review and improve the whole assessment process. We have focused on the discovery of behavioral patterns of learners and conceptual relationships among test items. Furthermore, we have led several experiments in our faculty in order to assess the whole approach. In particular, by analyzing the data visualization charts, we have detected several previously unknown test strategies used by the learners. Last, we have detected several correlations among questions, which gave us useful feedbacks on the test quality.
An important step in the design of visual languages is the specification of the graphical objects and the composition rules for constructing feasible visual sentences. The presence of different ...typologies of visual languages, each with specific graphical and structural characteristics, yields the need to have models and tools that unify the design steps for different types of visual languages. To this aim, in this paper we present a formal framework of visual language classes. Each class characterizes a family of visual languages based upon the nature of their graphical objects and composition rules. The framework has been embedded in the Visual Language Compiler–Compiler (VLCC), a graphical system for the automatic generation of visual programming environments.
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