Aseptic Meningitis in Oral Medicine: Exploring the Key Elements for a Challenging Diagnosis: A Review of the Literature and Two Case Reports

Aseptic meningitis (AM) is a potentially severe and life-threatening disease characterized by meningeal inflammation, usually with mononuclear pleocytosis. It represents a challenging and controversial issue in medicine for multiple etiologies, classification, and difficult diagnosis in the face of nonspecific sets of signs and symptoms. In the area of interest of oral medicine, in specific clusters of patients, even if rare, the occurrence of aseptic meningitis can pose a diagnostic and management dilemma in the following potential etiologies: (i) systemic diseases with oral and meningeal involvement, which include Behçet’s disease and Sjögren syndrome; (ii) drug-induced aseptic meningitis; (iii) aseptic viral meningitis, mostly related to herpes simplex virus infection and hand, foot, and mouth disease, caused by enteroviruses. In this review, clinical manifestations, diagnostic methodologies, incidence, treatment, and prognosis for each of these clinical entities are provided. Furthermore, two illustrative case reports are described: a patient suffering from recurrent oral ulcers, in which a sudden onset of AM allows us to diagnose Neuro Behçet’s disease, and a patient affected by pemphigus vulgaris, manifesting a drug-induced AM. Exploring this complex clinical entity scenario, it is clear that an oral medicine specialist has a place on any multidisciplinary team in making such a challenging diagnosis

A HPC and Grid enabling framework for genetic linkage analysis of SNPs

Understanding the structure, function and development of the human genome is a key factor to improve the quality of life. In order to achieve this goal developing and using a modern ICT infrastructure is essential, and can exploit next generation High Performance Computing (HPC) systems beyond the Petaflop scale in a collaborative and efficient way. The genetic linkage analysis of Single Nucleotide Polymorphism (SNP) markers has recently become a very popular approach for genetic epidemiology and population studies, aiming to discover the genetic correlation in complex diseases. The high computational cost and memory requirements of the major algorithms proposed in the literature make analyses of medium/large data sets very hard on a single CPU. A Grid based facility has hence been set up upon a high-performance infrastructure, the EGEE Grid, in order to create a tool for achieving whole-genome linkage analysis

A HPC and Grid enabling framework for genetic linkage analysis of SNPs

Understanding the structure, function and development of the human genome is a key factor to improve the quality of life. In order to achieve this goal developing and using a modern ICT infrastructure is essential, and can exploit next generation High Performance Computing (HPC) systems beyond the Petaflop scale in a collaborative and efficient way. The genetic linkage analysis of Single Nucleotide Polymorphism (SNP) markers has recently become a very popular approach for genetic epidemiology and population studies, aiming to discover the genetic correlation in complex diseases. The high computational cost and memory requirements of the major algorithms proposed in the literature make analyses of medium/large data sets very hard on a single CPU. A Grid based facility has hence been set up upon a high-performance infrastructure, the EGEE Grid, in order to create a tool for achieving whole-genome linkage analysis

A study of gas contaminants and interaction with materials in RPC closed loop systems

Resistive Plate Counters (RPC) detectors at the Large Hadron Collider (LHC) experiments use gas recirculation systems to cope with large gas mixture volumes and costs. In this paper a long-term systematic study about gas purifiers, gas contaminants and detector performance is discussed. The study aims at measuring the lifetime of purifiers with unused and used cartridge material along with contaminants release in the gas system. During the data-taking the response of several RPC double-gap detectors was monitored in order to characterize the correlation between dark currents, filter status and gas contaminants

Genetic constraints for thermal coadaptation in Drosophila subobscura

<p>Abstract</p> <p>Background</p> <p>Behaviour has been traditionally viewed as a driver of subsequent evolution because behavioural adjustments expose organisms to novel environments, which may result in a correlated evolution on other traits. In <it>Drosophila subobscura</it>, thermal preference and heat tolerance are linked to chromosomal inversion polymorphisms that show parallel latitudinal clines worldwide, such that "cold-climate" ("warm-climate") chromosome arrangements collectively favour a coherent response to colder (warmer) settings as flies carrying them prefer colder (warmer) conditions and have lower (higher) knock out temperatures. Yet, it is not clear whether a genetic correlation between thermal preference and heat tolerance can partially underlie such response.</p> <p>Results</p> <p>We have analyzed the genetic basis of thermal preference and heat tolerance using isochromosomal lines in <it>D. subobscura</it>. Chromosome arrangements on the O chromosome were known to have a biometrical effect on thermal preference in a laboratory temperature gradient, and also harbour several genes involved in the heat shock response; in particular, the genes <it>Hsp68 </it>and <it>Hsp70</it>. Our results corroborate that arrangements on chromosome O affect adult thermal preference in a laboratory temperature gradient, with cold-climate O_stcarriers displaying a lower thermal preference than their warm-climate O₃₊₄and O₃₊₄₊₈counterparts. However, these chromosome arrangements did not have any effect on adult heat tolerance and, hence, we putatively discard a genetic covariance between both traits arising from linkage disequilibrium between genes affecting thermal preference and candidate genes for heat shock resistance. Nonetheless, a possible association of juvenile thermal preference and heat resistance warrants further analysis.</p> <p>Conclusions</p> <p>Thermal preference and heat tolerance in the isochromosomal lines of <it>D. subobscura </it>appear to be genetically independent, which might potentially prevent a coherent response of behaviour and physiology (i.e., coadaptation) to thermal selection. If this pattern is general to all chromosomes, then any correlation between thermal preference and heat resistance across latitudinal gradients would likely reflect a pattern of correlated selection rather than genetic correlation.</p

Knowledge of Brazilian dentists and students in treating dentine hypersensitivity

Objective: To evaluate knowledge of undergraduates and qualified dentists from a Brazilian Dental School in treating Dentine Hypersensitivity (DH). Methodology: Data obtained from a 22-item questionnaire were analysed and arranged in distribution figures. Results: Of 100 respondents, 66.3% indicated that up to 25% of their patients had DH; 41.7%, that the duration of discomfort was up to eight weeks; 78.4%, that they examined a patient with DH within the last two-four weeks; and 70.4%, that this was done after the patient initiated the conversation on DH. Most of participants responded DH affects patients’ quality of life, and its aetiology was attrition, exposed dentine, occlusal interference, gingival recession or abrasion. The most common ways to diagnose DH were sensitivity history analysis, clinical examination, clinical testing and probing; and conflicting conditions were fractured restoration, bleaching sensitivity, marginal leakage, chipped tooth and periodontal disease. Furthermore, 82.5% and 78.7% of respondents indicated they were confident in diagnosing DH and providing advice to patients, but only 38.8% identified hydrodynamic theory as its underlying mechanism. To evaluate pain from DH they considered self-assessment, dental examination, dietary analysis and thermal assessment; and as recommendations, the use of desensitizing dentifrices, education on toothbrushing, in-office application of desensitizing products, and restorations. Conclusion: There is still confusion concerning the aetiology, the diagnosis and the subsequent management of DH, and both students and qualified dentists need better education

Role of combined DWIBS/3D-CE-T1w whole-body MRI in tumor staging: Comparison with PET-CT

Objectives: To assess the diagnostic performance of whole-body magnetic resonance imaging (WB-MRI) by diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in malignant tumor detection and the potential diagnostic advantages in generating fused DWIBS/3D-contrast enhanced T1w (3D-CE-T1w) images. Methods: 45 cancer patients underwent 18F-FDG PET-CT and WB-MRI for staging purpose. Fused DWIBS/3D-CE T1w images were generated off-line. 3D-CE-T1w, DWIBS images alone and fused with 3D-CE T1w were compared by two readers groups for detection of primary diseases and local/distant metastases. Diagnostic performance between the three WB-MRI data sets was assessed using receiver operating characteristic (ROC) curve analysis. Imaging exams and histopathological results were used as standard of references. Results: Areas under the ROC curves of DWIBS vs. 3D-CE-T1w vs. both sequences in fused fashion were 0.97, 0.978, and 1.00, respectively. The diagnostic performance in tumor detection of fused DWIBS/3DCE- T1w images were statistically superior to DWIBS (p < 0.001) and 3D-CE-T1w (p ≤ 0.002); while the difference between DWIBS and 3D-CE-T1w did not show statistical significance difference. Detection rates of malignancy did not differ between WB-MRI with DWIBS and 18F-FDG PET-CT. Conclusion: WB-MRI with DWIBS is to be considered as alternative tool to conventional whole-body methods for tumor staging and during follow-up in cancer patients

The effect of acute exercise on cognitive performance in children with and without ADHD

Background: Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder that affects approximately 11% of children in the United States. Research supports that a single session of exercise benefits cognitive performance by children, and a limited number of studies have demonstrated that these effects can also be realized by children with ADHD. The purpose of this study was to examine the effect of acute exercise on cognitive performance by children with and without ADHD. Methods: Children with and without ADHD were asked to perform cognitive tasks on 2 days following treatment conditions that were assigned in a random, counterbalanced order. The treatment conditions consisted of a 30-min control condition on 1 day and a moderate intensity exercise condition on the other day.Results Exercise significantly benefited performance on all three conditions of the Stroop Task, but did not significantly affect performance on the Tower of London or the Trail Making Test. Conclusion: Children with and without ADHD realize benefits in speed of processing and inhibitory control in response to a session of acute exercise, but do not experience benefits in planning or set shifting

Unraveling the effect of proliferative stress in vivo in hematopoietic stem cell gene therapy mouse study

The hematopoietic system of patients enrolled in hematopoietic stem cells (HSC) gene therapy (GT) treatments is fully reconstituted upon autologous transplantation of engineered stem cells. HSCs highly proliferate up to full restoration of homeostasis and compete for niche homing and engraftment. The impact of the proliferation stress in HSC on genetic instability remains an open question that cured patients advocate for characterizing long-term safety and efficacy. The accumulation of somatic mutations has been widely used as a sensor of proliferative stress. Vector integration site (IS) can be used as a molecular tool for clonal identity, inherited by all HSC progeny, to uncover lineage dynamics in vivo at single-cell level. Here we characterized at single-clone granularity the proliferative stress of HSCs and their progeny over time by measuring the accumulation of mutations from the DNA of each IS. To test the feasibility of the approach, we set-up an experimental framework that combines tumor-prone Cdkn2a-/- and wild type (WT) mouse models of HSC-GT and molecular analyses on different hematopoietic cell lineages after transplantation of HSCs transduced with genotoxic LV (LV.SF.LTR) or GT-like non-genotoxic LV (SIN.LV.PGK). The Cdkn2a-/- mouse model provided the experimental conditions to detect the accumulation of somatic mutations, since the absence of p16INK4A and p19ARF enhances the proliferative potential of cells that have acquired oncogenic mutations. As expected, mice transplanted with Cdkn2a-/- Lin- cells marked with LV.SF.LTR (N=24) developed tumors significantly earlier compared to mock (N=20, p&lt;0.0001), while mice treated with SIN. LV.PGK (N=23) did not. On the other side, mice that received WT Lin- cells treated with LV.SF.LTR (N=25) or SIN.LV.PGK (N=24) vector have not developed tumors. Given this scenario, we expect that Cdkn2a-/- Lin- cells transduced with LV.SF.LTR are associated with higher mutation rates compared to the SIN.LV.PGK group and wild type control mice. The composition of peripheral blood, lymphoid (B and T) and myeloid compartments was assessed by FACS on samples collected every 4 weeks and IS identification. More than 200,000 IS have been recovered. To identify the presence of somatic mutations, the genomic portions of sequencing reads flanking each different IS were analyzed with VarScan2. The accumulation rates of mutations have been evaluated by our new Mutation Index (MI) which normalizes the number of mutations by clones and coverage. Considering that a large portion of IS has been discarded since not covered by a minimum number of 5 unique reads (genomes), the remaining number of IS contained &gt;90% of reads in each group. The MI increased over time in both LV.SF.LTR groups, with higher values for the Cdkn2a-/-. On the other hand, treatment with SIN.LV.PGK resulted in lower MI in both groups compared to LV.SF.LTR groups, reflecting the higher clonal composition of the cells treated with the SIN.LV.PGK and the phenomenon of insertional mutagenesis in the LV.SF.LTR. Moreover, the higher MI values of the SIN.LV.PGK Cdkn2a-/- group compared with the WT group proved the induction of DNA fragility. Our results showed that the analysis of the accumulation of somatic mutations at single clone unraveled HSC proliferation stress in vivo, combining for the first time the analysis of acquired mutations with IS. We are now applying our model to different clinical trials, and studying HSCs sub- clonal trees by symmetric divisions, previously indistinguishable by IS only. Our study will open the doors to in vivo long-term non-invasive studies of HSC stability in patients