Nouveau spectre des troubles cognitifs liés à l'infection par le VIH à l'ère des trithérapies [New spectrum of HIV-associated cognitive disorders in the HAART era]

Highly active anti-retroviral therapy (HAART) has almost abolished HIV-related mortality and serious opportunistic diseases; among them, AIDS-related dementia. However, minor forms of cognitive dysfunction, have not disappeared, and even increased in frequency. Ageing of HIV+ patients, insufficient penetration of anti-viral drugs into the brain with continuous low-grade viral production and inflammation may play a role. Minor cognitive dysfunction in HIV infection shares some clinical and pathophysiological features with neuro-degenerative diseases, in particular Alzheimers disease. It can thus be postulated that, such in Alzheimer disease, anti-cholinesterase drugs might also be efficacious in AIDS-related minor cognitive dysfunction. This hypothesis has not been tested yet however A clinical trial using ravistigmine is starting this spring in patients with HIV-associated cognitive dysfunction in Geneva and Lausanne.

3D noise power spectrum applied on clinical mdct scanners: effects of reconstruction algorithms and reconstruction filters

The noise power spectrum (NPS) is the reference metric for understanding the noise content in computed tomography (CT) images. To evaluate the noise properties of clinical multidetector (MDCT) scanners, local 2D and 3D NPSs were computed for different acquisition reconstruction parameters.A 64- and a 128-MDCT scanners were employed. Measurements were performed on a water phantom in axial and helical acquisition modes. CT dose index was identical for both installations. Influence of parameters such as the pitch, the reconstruction filter (soft, standard and bone) and the reconstruction algorithm (filtered-back projection (FBP), adaptive statistical iterative reconstruction (ASIR)) were investigated. Images were also reconstructed in the coronal plane using a reformat process. Then 2D and 3D NPS methods were computed.In axial acquisition mode, the 2D axial NPS showed an important magnitude variation as a function of the z-direction when measured at the phantom center. In helical mode, a directional dependency with lobular shape was observed while the magnitude of the NPS was kept constant. Important effects of the reconstruction filter, pitch and reconstruction algorithm were observed on 3D NPS results for both MDCTs. With ASIR, a reduction of the NPS magnitude and a shift of the NPS peak to the low frequency range were visible. 2D coronal NPS obtained from the reformat images was impacted by the interpolation when compared to 2D coronal NPS obtained from 3D measurements.The noise properties of volume measured in last generation MDCTs was studied using local 3D NPS metric. However, impact of the non-stationarity noise effect may need further investigations.

Clinical spectrum of tuberculous optic neuropathy.

PURPOSE: Tuberculous optic neuropathy may follow infection with Mycobacterium tuberculosis or administration of the bacille Calmette-Guerin. However, this condition is not well described in the ophthalmic literature. METHODS: Ophthalmologists, identified through professional electronic networks or previous publications, collected standardized clinical data relating to 62 eyes of 49 patients who they had managed with tuberculous optic neuropathy. RESULTS: Tuberculous optic neuropathy was most commonly manifested as papillitis (51.6 %), neuroretinitis (14.5 %), and optic nerve tubercle (11.3 %). Uveitis was an additional ocular morbidity in 88.7 % of eyes. In 36.7 % of patients, extraocular tuberculosis was present. The majority of patients (69.4 %) had resided in and/or traveled to an endemic area. Although initial visual acuity was 20/50 or worse in 62.9 % of 62 eyes, 76.7 % of 60 eyes followed for a median of 12 months achieved visual acuities of 20/40 or better. Visual field defects were reported for 46.8 % of eyes, but these defects recovered in 63.2 % of 19 eyes with follow-up. CONCLUSION: Visual recovery from tuberculous optic neuropathy is common, if the diagnosis is recognized and appropriate treatment is instituted. A tuberculous etiology should be considered when evaluating optic neuropathy in persons from endemic areas.

Mapping the human connectome at multiple scales with diffusion spectrum MRI.

The global structural connectivity of the brain, the human connectome, is now accessible at millimeter scale with the use of MRI. In this paper, we describe an approach to map the connectome by constructing normalized whole-brain structural connection matrices derived from diffusion MRI tractography at 5 different scales. Using a template-based approach to match cortical landmarks of different subjects, we propose a robust method that allows (a) the selection of identical cortical regions of interest of desired size and location in different subjects with identification of the associated fiber tracts (b) straightforward construction and interpretation of anatomically organized whole-brain connection matrices and (c) statistical inter-subject comparison of brain connectivity at various scales. The fully automated post-processing steps necessary to build such matrices are detailed in this paper. Extensive validation tests are performed to assess the reproducibility of the method in a group of 5 healthy subjects and its reliability is as well considerably discussed in a group of 20 healthy subjects.

Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders.

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament.

Prevalence, prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe.

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990-2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100,000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.

Fully Distributed Cooperative Spectrum Sensing for Cognitive Radio Networks

Cognitive radio networks (CRN) sense spectrum occupancy and manage themselves to operate in unused bands without disturbing licensed users. The detection capability of a radio system can be enhanced if the sensing process is performed jointly by a group of nodes so that the effects of wireless fading and shadowing can be minimized. However, taking a collaborative approach poses new security threats to the system as nodes can report false sensing data to force a wrong decision. Providing security to the sensing process is also complex, as it usually involves introducing limitations to the CRN applications. The most common limitation is the need for a static trusted node that is able to authenticate and merge the reports of all CRN nodes. This paper overcomes this limitation by presenting a protocol that is suitable for fully distributed scenarios, where there is no static trusted node.

Spectrum Sharing Models in Cognitive Radio

Spectrum scarcity demands thinking new ways tomanage the distribution of radio frequency bands so that its use is more effective. The emerging technology that can enable this paradigm shift is the cognitive radio. Different models fororganizing and managing cognitive radios have emerged, all with specific strategic purposes. In this article we review the allocation spectrum patterns of cognitive radio networks andanalyse which are the common basis of each model.We expose the vulnerabilities and open challenges that still threaten the adoptionand exploitation of cognitive radios for open civil networks.

Personality traits are associated with acute major depression across the age spectrum.

Objectives: Psychological predictors, such as personality traits, have aroused growing interest as possible predictors of late-life depression outcome in old age. It remains, however, unclear whether the cross-sectional relationship between personality traits and depression occurrence reported in younger samples is also present in the elderly. Methods: Comparisons amongst 79 outpatients with DSM-IV major depression and 102 healthy controls included assessment of the five-factor model of personality (NEO PI-R), socio-demographic variables, physical health status, as well as depression features. Two sub-groups were considered, defined as young (25-50 years) and old (60-85 years) patients. Results: Depressed patients showed significantly higher levels of Neuroticism and lower levels of Extraversion, Openness to Experience and Conscientiousness compared to controls. Sequential logistic regression models confirmed that the combination of increased physical burden, levels of dependency, and increased Neuroticism strongly predicts the occurrence of acute depressive symptoms. In contrast, the levels of Neuroticism did not allow for differentiating late-life from young age depression. Increased physical burden and decreased depression severity were the main predictors for this distinction. Conclusion: Our data indicate that personality factors and depression are related, independently of patients' age. Differences in this relationship are mainly due to the intensity of depressive symptoms rather than the patients' life period. They also stress the need to consider physical health, level of dependency and severity of symptoms when studying the relationship between personality traits and mood disorders.

Spectrum of ocular digoxin toxicity in the elderly: A case report

Introduction: We report a case of digoxin intoxication with severe visual symptoms. Patients (or Materials) and Methods: Digoxin 0.25 mg QD for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 mL/min. Within 2 to 3 weeks, she developed nausea, vomiting, and dysphagia, and began complaining of snowy and blurry vision, photopsia, dyschromatopsia, aggravated bedtime visual and proprioceptive illusions (she felt as being on a boat), and colored hallucinations. She consulted her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, impaired autonomy led her to be admitted to the emergency department. Results: Digoxin intoxication was confirmed by a high plasma level measured on admission (5.7 μg/L; reference range, 0.8-2 μg/L). After stopping digoxin, general symptoms resolved in a few days, but visual symptoms persisted. Ophtalmologic care and follow-up diagnosed digoxin intoxication superimposed on pre-existing left eye (LE) cataract, dry age-related macular degeneration (DMLA), and Charles Bonnet syndrome. Visual acuity was 0.4 (right eye, RE) and 0.5 (LE). Ocular fundus was physiologic except for bilateral dry DMLA. Dyschromatopsia was confirmed by poor results on Ishihara test (1/13 OU). Computerized visual field results revealed nonspecific diffuse alterations. Full-field electroretinogram (ERG) showed moderate diffuse rod and cone dysfunction. Visual symptoms progressively improved over the next 2 months, but ERG did not. Complete resolution was not expected due to the pre-existing eye disease. The patient was finally discharged home after a 5-week hospital stay. Conclusion: Digoxin intoxication can go unrecognized by clinicians, even in a typical presentation. The range of potential visual symptoms is far greater than isolated xanthopsia (yellow vision) classically described in textbooks. Newly introduced drugs and all symptoms must be actively sought after, because they significantly affect quality of life and global functioning, especially in the elderly population, most liable not to mention them.

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in seven unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits, thereby interfering with integrin maturation and/or function. Our study extends knowledge of GT and the pathophysiology of an integrin.