Current clinical management of CIDP with immunoglobulins in France: An expert opinion.

Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.

Clinical follow-up of 411 patients with relapsing and progressive multiple sclerosis 10 years after discontinuing mitoxantrone treatment: a real-life cohort study.

BACKGROUND AND PURPOSE: Mitoxantrone (MITOX) has been used to treat patients with aggressive multiple sclerosis (MS) for decades. We aimed to describe the effectiveness and adverse events over 10 years post-MITOX in patients with relapsing and progressive MS from an exhaustive real-life database. METHODS: Data from patients who received MITOX before 1 January 2006 were collected from the MS Lorraine registry. Expanded Disability Status Scale (EDSS) scores and annual relapse rates (ARRs) year by year during follow-up and the year prior to MITOX were compared. Time to the first relapse and a 1-point increase in EDSS score were used in Cox multivariate models to find associations with potential predictive factors. RESULTS: A total of 411 patients were included. The ARR for the 155 relapsing patients had decreased from 2.0 (SD 1.20) the year before treatment to 0.3 (SD 0.31) by year 10 (P < 0.0001). The EDSS score increased from 2.8 (SD 1.44) to 4.8 (SD 1.90) by year 10 (P < 0.0001). A high ARR at MITOX initiation was associated with a longer time to a 1-point increase in EDSS score (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99; P = 0.04). The EDSS score in 256 progressive patients increased from 5.0 (SD 1.33) to 6.5 (SD 1.26) by year 10 (P < 0.0001). We identified four cases of acute myeloid leukemias. CONCLUSIONS: Patients with the most active forms of MS are the most likely to benefit from MITOX in the long term.

Classification and diagnostic criteria for demyelinating diseases of the central nervous system: Where do we stand today?

The diagnosis of multiple sclerosis (MS) and other demyelinating diseases of the central nervous system is challenging, and although the currently available biological and imaging tools offer considerable support to physicians, these tools often fail to provide a simple and final answer at the time of a first event. Thus, sets of diagnostic criteria have been published and tested on patient cohorts, and are now used in clinical trials and in daily clinical practice. These criteria have evolved over time to take into account physicians' and patients' needs, along with emerging paraclinical tests. The different presentations of MS have given rise to the use of a common classification system to identify patient profiles and adapt care protocols accordingly. This article reviews the various classifications of the forms and diagnostic criteria of MS and related syndromes, including neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSDs), acute disseminated (demyelinating) encephalomyelitis (ADEM) and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Also discussed is their validity in the light of the currently available literature.

Interhemispheric inhibition in human wrist muscles.

The interhemispheric interactions between homologous wrist extensor and flexor muscles representations in the right and left primary cortex (M1) were studied using a paired-pulse transcranial magnetic stimulation in healthy subjects. The magnitude of interhemispheric inhibition (IHI) was studied in 9 right-handed subjects at short (10 ms, SIHI) and long (40 ms, LIHI) interstimulus intervals between the magnetic conditioning (CS) and test stimulus in the motor dominant to non-dominant cortex and vice versa, while the right or left hand was at rest or performing a unimanual sustained tonic contraction (holding a pen with the hand contralateral to the CS). A bidirectional powerful interhemispheric inhibition could be elicited at the short and long IHI phases (SIHI and LIHI) in wrist extensor and flexor muscles in most of the subjects at rest. SIHI but not LIHI was significantly bidirectionally reduced during unimanual contraction of the hand contralateral to the CS stimulation in comparison with rest. The amount of IHI after the stimulation of the "non-dominant" right hemisphere was not reduced in comparison with IHI after stimulation of the "dominant" left hemisphere whatever the active or resting condition. IHI directed to the wrist muscles had a similar level than IHI directed to digit muscles (FDI) at rest. Our data indicate that contralateral wrist muscles activity evokes a global, bidirectional reduction in IHI which was more pronounced for SIHI. These results provide additional evidence that changes in interhemispheric interactions between the M1s are involved in the control of unimanual movements including suppression of unwanted motor activity in the opposite limb during unilateral movements.

Absolute cross sections for vibrational excitations of cytosine by low energy electron impact.

The absolute cross sections (CSs) for vibrational excitations of cytosine by electron impact between 0.5 and 18 eV were measured by electron-energy loss (EEL) spectroscopy of the molecule deposited at monolayer coverage on an inert Ar substrate. The vibrational energies compare to those that have been reported from IR spectroscopy of cytosine isolated in Ar matrix, IR and Raman spectra of polycrystalline cytosine, and ab initio calculation. The CSs for the various H bending modes at 142 and 160 meV are both rising from their energy threshold up to 1.7 and 2.1 × 10(-17) cm(2) at about 4 eV, respectively, and then decrease moderately while maintaining some intensity at 18 eV. The latter trend is displayed as well for the CS assigned to the NH(2) scissor along with bending of all H at 179 meV. This overall behavior in electron-molecule collision is attributed to direct processes such as the dipole, quadrupole, and polarization contributions, etc. of the interaction of the incident electron with a molecule. The CSs for the ring deformation at 61 meV, the ring deformation with N-H symmetric wag at 77 meV, and the ring deformations with symmetric bending of all H at 119 meV exhibit common enhancement maxima at 1.5, 3.5, and 5.5 eV followed by a broad hump at about 12 eV, which are superimposed on the contribution due to the direct processes. At 3.5 eV, the CS values for the 61-, 77-, and 119-meV modes reach 4.0, 3.0, and 4.5 × 10(-17) cm(2), respectively. The CS for the C-C and C-O stretches at 202 meV, which dominates in the intermediate EEL region, rises sharply until 1.5 eV, reaches its maximum of 5.7 × 10(-17) cm(2) at 3.5 eV and then decreases toward 18 eV. The present vibrational enhancements, correspond to the features found around 1.5 and 4.5 eV in electron transmission spectroscopy (ETS) and those lying within 1.5-2.1 eV, 5.2-6.8 eV, and 9.5-10.9 eV range in dissociative electron attachment (DEA) experiments with cytosine in gas phase. While the ETS features are ascribed to shape resonances associated with the electron occupation of the second and third antibonding π-orbitals of the molecule in its ground state, the correspondence with DEA features suggests the existence of common precursor anion states decaying with certain probabilities into the vibrationally excited ground state.

The impact of environmental factors on the evolution of brain size in carnivorans.

The reasons why some animals have developed larger brains has long been a subject of debate. Yet, it remains unclear which selective pressures may favour the encephalization and how it may act during evolution at different taxonomic scales. Here we studied the patterns and tempo of brain evolution within the order Carnivora and present large-scale comparative analysis of the effect of ecological, environmental, social, and physiological variables on relative brain size in a sample of 174 extant carnivoran species. We found a complex pattern of brain size change between carnivoran families with differences in both the rate and diversity of encephalization. Our findings suggest that during carnivorans' evolution, a trade-off have occurred between the cognitive advantages of acquiring a relatively large brain allowing to adapt to specific environments, and the metabolic costs of the brain which may constitute a disadvantage when facing the need to colonize new environments.

[Fabry disease: A review]. / Maladie de Fabry : quand y penser ?

Fabry disease is the second most frequent lysosomal storage disorder. It is a X-linked genetic disease secondary to alpha-galactosidase A enzyme deficiency. This is a progressive and systemic disease that affects both males and females. Classical symptoms and organ involvements are acral pain crisis, cornea verticillata, hypertrophic cardiomyopathy, stroke and chronic kidney disease with proteinuria. Nevertheless, organ damages can be missing or pauci-symptomatic and other common symptoms are poorly recognised, such as gastrointestinal or ear involvement. In classical Fabry disease, symptoms first appear during childhood or teenage in males, but later in females. Patients may have non-classical or late-onset Fabry disease with delayed manifestations or with single-organ involvement. Recognition of Fabry disease is important because treatments are available, but it may be challenging. Diagnosis is easy in males, with dosage of alpha-galactosidase A enzyme activity into leukocytes, but more difficult in females who can express normal residual activity. Other plasmatic biomarkers, such as lyso-globotriaosylceramide (lyso-Gb3), are interesting in females, but need to be associated with GLA gene analysis. In this review, we aimed at summarize the main clinical manifestations of Fabry disease and propose a practical algorithm to know how to diagnose this complex disease.

Rapid elevation of Inos and decreases in abundance of other proteins at pupal diapause termination in the flesh fly Sarcophaga crassipalpis.

We analyzed changes in brain proteins 24 h after pupal diapause termination in Sarcophaga crassipalpis by a combination of 2-dimensional gel electrophoresis and mass spectrometry. The proteome analysis revealed significant changes in 20 proteins, 11 of which represented >or=2.5-fold changes. Three proteins were present only in the brains of diapausing pupae. Among the most abundant proteins that showed a change, 1 was more abundant, 7 were less abundant, and 2 were absent following diapause termination. The protein that increased in abundance following diapause termination showed highest identity to myo-inositol-1-phosphate synthase (Inos). Proteins that decreased at diapause termination included those showing highest identities to fatty acid binding protein, CG2331-PA, twinstar, catalase, and a histone. Proteins absent at diapause termination included ribosomal protein L17A and one unnamed protein. An increase of Inos protein level was confirmed using Western blot analysis. Attempts to terminate diapause by injection of several Inos-related metabolites failed, thus suggesting that the elevation of Inos at diapause termination is downstream of the physiological regulation that initiates development.

The molecular physiology of increased egg desiccation resistance during diapause in the invasive mosquito, Aedes albopictus.

Photoperiodic diapause is a crucial adaptation to seasonal environmental variation in a wide range of arthropods, but relatively little is known regarding the molecular basis of this important trait. In temperate populations of the mosquito Aedes albopictus, exposure to short-day (SD) lengths causes the female to produce diapause eggs. Tropical populations do not undergo a photoperiodic diapause. We identified a fatty acyl coA elongase transcript that is more abundant under SD versus long-day (LD) photoperiods in mature oocyte tissue of replicate temperate, but not tropical, A. albopictus populations. Fatty acyl CoA elongases are involved in the synthesis of long chain fatty acids (hydrocarbon precursors). Diapause eggs from a temperate population had one-third more surface hydrocarbons and one-half the water loss rates of non-diapause eggs. Eggs from a tropical population reared under SD and LD photoperiods did not differ in surface hydrocarbon abundance or water loss rates. In both a temperate and tropical population, composition of hydrocarbon chain lengths did not differ between eggs from SD versus LD conditions. These results implicate the expression of fatty acyl coA elongase and changes in quantity, but not composition, of egg surface hydrocarbons as important components of increased desiccation resistance during diapause in A. albopictus.

Absolute cross sections for electronic excitations of cytosine by low energy electron impact.

The absolute cross sections (CSs) for electronic excitations of cytosine by electron impact between 5 and 18 eV were measured by electron-energy-loss (EEL) spectroscopy of the molecule deposited at low coverage on an inert Ar substrate. The lowest EEL features found at 3.55 and 4.02 eV are ascribed to transitions from the ground state to the two lowest triplet 1 (3)A(')(π→π(∗)) and 2 (3)A(')(π→π(∗)) valence states of the molecule. Their energy dependent CSs exhibit essentially a common maximum at about 6 eV with a value of 1.84×10(-17) cm(2) for the former and 4.94×10(-17) cm(2) for the latter. In contrast, the CS for the next EEL feature at 4.65 eV, which is ascribed to the optically allowed transition to the 2 (1)A(')(π→π(∗)) valence state, shows only a steep rise to about 1.04×10(-16) cm(2) followed by a monotonous decrease with the incident electron energy. The higher EEL features at 5.39, 6.18, 6.83, and 7.55 eV are assigned to the excitations of the 3 (3,1)A(')(π→π(∗)), 4 (1)A(')(π→π(∗)), 5 (1)A(')(π→π(∗)), and 6 (1)A(')(π→π(∗)) valence states, respectively. The CSs for the 3 (3,1)A(') and 4 (1)A(') states exhibit a common enhancement at about 10 eV superimposed on a more or less a steep rise, reaching, respectively, a maximum of 1.27 and 1.79×10(-16) cm(2), followed by a monotonous decrease. This latter enhancement and the maximum seen at about 6 eV in the lowest triplet states correspond to the core-excited electron resonances that have been found by dissociative electron attachment experiments with cytosine in the gas phase. The weak EEL feature found at 5.01 eV with a maximum CS of 3.8×10(-18) cm(2) near its excitation threshold is attributed to transitions from the ground state to the 1 (3,1)A(")(n→π(∗)) states. The monotonous rise of the EEL signal above 8 eV is attributed to the ionization of the molecule. It is partitioned into four excitation energy regions at about 8.55, 9.21, 9.83, and 11.53 eV, which correspond closely to the ionization energies of the four highest occupied molecular orbitals of cytosine. The sum of the ionization CS for these four excitation regions reaches a maximum of 8.1×10(-16) cm(2) at the incident energy of 13 eV.

[French regulation of medical research]. / Réglementation de la recherche médicale en France.

In France, clinical research involving human beings is regulated by the Jardé's law since November 2016. The law distinguishes interventional and non-interventional studies. Both need to be authorized by a Persons Protection Committee. Studies performed on medical data collected during standard clinical care are not considered as studies involving human beings. Medical data are personal data. French Data Protection Authority National has an important role, guarantying the respect of regulation on personal data. We summarize in this article the different types of studies and the role of regulatory authorities.

[Mucopolysaccharidosis: A review]. / Mucopolysaccharidoses : quand y penser ?

Mucopolysaccharidosis are lysosomal storage diseases, secondary to the accumulation of mucopolysaccharides. Type 1 mucopolysaccharidosis is the most common form and affects between 0.69 and 1.66 newborns per 100,000. The severity of mucopolysaccharidosis is variable with lethal forms in utero and attenuated forms diagnosed in adults. The most common symptoms are short stature, facial dysmorphism, chronic articular pains that can mimic chronic inflammatory rheumatism, axial and peripheral bone involvement, hepatosplenomegaly and an early carpal tunnel. Depending on the type of mucopolysaccharidosis, corneal, cerebral or cardiac involvements are possible. Screening is based on the analysis of urinary glycosaminoglycans. The deficient enzyme assay and the gene analysis confirm the diagnosis. Mucopolysaccharidosis recognition is important for patient management and family screening. In addition, specific enzyme replacement therapy exists for certain types of mucopolysaccharidosis. Role of clinician is important to evoke and diagnose mucopolysaccharidosis.

Ultrastructural alterations in Fusarium sambucinum and Heterobasidion annosum treated with aluminum chloride and sodium metabisulfite.

Aluminum chloride (AlCl(3)) and sodium metabisulfite (Na(2)S(2)O(5)) have received increasing attention as antifungal agents for the control of plant diseases. In an effort to understand their toxic action on fungi, ultrastructural changes and membrane damage in Fusarium sambucinum (Ascomycota) and Heterobasidion annosum (Basidiomycota) in response to salt exposure was investigated using transmission electron microscopy. Conidial membrane damage was quantified using SYTOX Green stain, which only enters altered membranes. The results showed that mortality of the conidia was generally closely associated with SYTOX stain absorption in F. sambucinum treated with Na(2)S(2)O(5) and in H. annosum treated with AlCl(3) or Na(2)S(2)O(5), suggesting that these salts cause membrane alterations. For both fungi, ultrastructural alterations in conidia treated with AlCl(3) and Na(2)S(2)O(5) included membrane retraction, undulation, and invagination. At higher concentrations or exposure periods to the salts, loss of membrane integrity, cytoplasmic leakage, and cell rupture were observed. Ultrastructural alterations and increased SYTOX stain absorption in salt-treated conidia appear consistent with a mode of action where AlCl(3) and Na(2)S(2)O(5) alter membrane integrity and permeability.

[Very early and early systemic sclerosis: An update]. / Mise au point sur les sclérodermies très précoces et précoces.

Classification criteria for systemic sclerosis evolved over the last three decades, allowing an earlier classification. In the late 2000s, the EULAR Scleroderma Trials and Research Group validated very early and early systemic sclerosis criteria. Raynaud phenomenon, anti-nuclear antibody positivity and the puffy fingers are "Red flags" that must lead to refer the patient to a specialist and benefit from a capillaroscopy and the specific autoantibodies. At the stage of very early systemic sclerosis, pulmonary, cardiac and digestive involvements may be present and must be screened. Herein, we detail very early and early systemic sclerosis criteria, as well as the predictive factors of evolution towards a systemic sclerosis.

Metabolomics reveals unique and shared metabolic changes in response to heat shock, freezing and desiccation in the Antarctic midge, Belgica antarctica.

The midge, Belgica antarctica Jacobs, is subjected to numerous environmental stressors during its 2-year life cycle on the Antarctic Peninsula, and in response it has evolved a suite of behavioral, physiological, and life-cycle modifications to counter these stressors, but thus far only a limited number of biochemical adaptations have been identified. In this study, we use a metabolomics approach to obtain a broad overview of changes in energy metabolism, amino acids, and polyols in response to three of the midge's major stresses: heat, freezing, and desiccation. Using GC-MS analysis, a total of 75 compounds were identified. Desiccation (50% water loss) elicited the greatest physiological response (as determined by principal components analysis) when compared to untreated controls, with many elevated metabolites from pathways of central carbohydrate metabolism and a decrease in free amino acids. When larvae were frozen (6h at -10 degrees C), alanine and aspartate increased as well as urea. Freezing also increased three polyols (glycerol, mannitol, erythritol), while desiccation increased only two polyols (glycerol, erythritol). Heating the midges for 1h at 30 degrees C elevated alpha-ketoglutarate and putrescine while suppressing glycerol, glucose, and serine levels. Freezing and desiccation elicited elevation of four shared metabolites, whereas no shared metabolites were elevated by heat. All three treatments resulted in a reduction in serine, potentially identifying this amino acid as a marker for stress in this species. A number of metabolic changes, especially those in the sugar and polyol pools, are adaptations that have potential to enhance survival during both cold and desiccation.

Mechanisms to reduce dehydration stress in larvae of the Antarctic midge, Belgica antarctica.

The Antarctic midge, Belgica antarctica, is exposed to frequent periods of dehydration during its prolonged larval development in the cold and dry Antarctic environment. In this study, we determined the water requirements of the larvae and the mechanisms it exploits to reduce the stress of drying. Larvae lost water at an exceptionally high rate (>10%/h) and tolerated losing a high portion (>70%) of their water content. Larvae were unable to absorb water from subsaturated water vapor (< or = 0.98 a(v)) to replenish their water stores, thus this midge relies exclusively on the intake of liquid water to increase its pool of body water and maintain water balance. To reduce dehydration stress, the midge employed a variety of mechanisms. Behaviorally, the larvae suppressed water loss by clustering. In response to slow dehydration, glycerol concentration increased 2-fold and trehalose concentration increased 3-fold, responses that are known to decrease the rate of water loss and increase dehydration tolerance. No changes in the mass of cuticular lipids occurred in response to desiccation, but the observed shift to longer hydrocarbons likely contributes to reduced water loss as the larvae dehydrate. As the larvae dehydrated, their oxygen consumption rate dropped, resulting in a reduction of water loss by respiration. Lastly, one bout of slow dehydration also enhanced the larva's ability to survive subsequent dehydration, suggesting that the larvae have the capacity for drought acclimation. Thus, these hydrophilic midge larvae prevent dehydration by multiple mechanisms that collectively reduce the water loss rate and increase dehydration tolerance.

[Acute pancreatitis due to hypercalcemia revealing adult T-cell leukemia]. / Une pancréatite aiguë révélant une leucémie/lymphome T de l'adulte.

INTRODUCTION: Hypercalcemia frequently occurs in the course of Adult T-cell leukemia/lymphoma (ATLL). We report the first case of acute pancreatitis revealing ATLL. EXEGESIS: A 41-year-old woman, without medical history, presented with acute pancreatitis. Physical examination found recent loss of weight, hepatosplenomegaly and generalised lymphoadenopathy. Biochemical tests showed severe hypercalcemia and the peripheral white blood cell count revealed an atypical lymphocytosis. ATLL was diagnosed by immunophenotypic and morphological analysis of circulating lymphocytes, bone marrow and lymphatic node biopsy. Level of serum parathyroid hormone-related protein was not increased. We discuss the mechanism of hypercalcemia in this context. CONCLUSION: In spite of the high prevalence of hypercalcemia in ATLL, acute pancreatitis revealing this pathology is an exceptional condition.