Unraveling the functional attributes of the language connectome: crucial subnetworks, flexibility and variability.

Language processing is a highly integrative function, intertwining linguistic operations (processing the language code intentionally used for communication) and extra-linguistic processes (e.g., attention monitoring, predictive inference, long-term memory). This synergetic cognitive architecture requires a distributed and specialized neural substrate. Brain systems have mainly been examined at rest. However, task-related functional connectivity provides additional and valuable information about how information is processed when various cognitive states are involved. We gathered thirteen language fMRI tasks in a unique database of one hundred and fifty neurotypical adults (InLang [Interactive networks of Language] database), providing the opportunity to assess language features across a wide range of linguistic processes. Using this database, we applied network theory as a computational tool to model the task-related functional connectome of language (LANG atlas). The organization of this data-driven neurocognitive atlas of language was examined at multiple levels, uncovering its major components (or crucial subnetworks), and its anatomical and functional correlates. In addition, we estimated its reconfiguration as a function of linguistic demand (flexibility) or several factors such as age or gender (variability). We observed that several discrete networks could be specifically shaped to promote key functional features of language: coding-decoding (Net1), control-executive (Net2), abstract-knowledge (Net3), and sensorimotor (Net4) functions. The architecture of these systems and the functional connectivity of the pivotal brain regions varied according to the nature of the linguistic process, gender, or age. By accounting for the multifaceted nature of language and modulating factors, this study can contribute to enriching and refining existing neurocognitive models of language. The LANG atlas can also be considered a reference for comparative or clinical studies involving various patients and conditions.

Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France.

OBJECTIVES: To assess the prevalence of resistance to rilpivirine and mutations at position 138 in reverse transcriptase and to identify associated epidemiological and biological characteristics. METHODS: This retrospective study included 238 patients with available HIV-1 nucleotide sequences analysed at the Laboratory of Virology at the University Hospital of Nancy between January 2011 and June 2013. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was evaluated according to the ANRS algorithm (version 23) and correlated with clinico-epidemiological and therapeutic data. The virus strains were analysed by evaluating the distance and distribution of the phylogenetic tree (MEGAv5). RESULTS: Among previously treated patients (111/238, 46.6%), 68/111 (61.3%) had received NNRTIs; all were rilpivirine-naive. The prevalence of rilpivirine resistance in the whole cohort was 12.6% (30/238), and was 10.2% (13/127) and 15.3% (17/111) in naive and pre-treated patients, respectively. The E138A mutation was the most frequent mutation associated with resistance to rilpivirine (P < 0.0001). The prevalence of the E138A mutation tended to increase over time, from 3.6% (2/55) during the first half of 2011 to 9.3% (4/43) during the first half of 2013 (P = 0.0614). Seven viral strains from seven naive male patients positive for the E138A mutation appeared in the same cluster. CONCLUSIONS: In our cohort of patients, we observed significantly increased resistance to rilpivirine, mostly because of the E138A mutation, probably due to an E138A strain circulating in newly diagnosed men who have sex with men. Taken together, our results emphasize the need to investigate the prevalence of rilpivirine resistance-associated mutations in the coming years both in France and abroad.

Large agminated cellular 'plaque-type' blue nevus surrounding the ear: a case and review.

Large or giant cellular blue nevi are usually congenital and represent a challenge for the physician. Close anatomic structures may be altered by the size of the moles. In this article, we report the case of an uncommon large, agminated, cellular blue nevus of the 'plaque type' in a 42-year-old female. Due to the risks of malignant melanoma development on a large or giant blue nevus, we highlight the importance of proper histopathological diagnosis. Furthermore, because of the possibility that the nevus may invade the bone and cerebral tissues, we discuss the indication of a radiological diagnosis. The accurate correlation to clinical and histopathological findings and appropriate multidisciplinary management can save the lives of patients.

HLA-B*51:79 is a novel allele associated with a conserved haplotype.

The B*51:79 allele displays a conserved haplotype association with HLA-A*68:01, C*01:02, DRB1*14:01 and DQB1*05:03.

[Management of basal cell carcinoma]. / Prise en charge du carcinome basocelulaaire.

Basal cell carcinoma is a major public health problem, because its incidence is high and due to its relationship to sun exposure. Early detection is pivotal in reducing its morbidity and an adequate therapeutic approach enables definitive healing of the disease in most cases. Conventional and micrographic surgery both are gold standard for non-superficial forms of the tumor. Other therapies are available or are under investigation, ranging from radiotherapy to modalities based on the understanding of molecular events leading to tumor development.

Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI.

Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.

Non-linear elastic properties of the lingual and facial tissues assessed by indentation technique. Application to the biomechanics of speech production.

This paper aims at characterizing the mechanical behavior of two human anatomical structures, namely the tongue and the cheek. For this, an indentation experiment was provided, by measuring the mechanical response of tongue and cheek tissues removed from the fresh cadaver of a 74 year old woman. Non-linear relationships were observed between the force applied to the tissues and the corresponding displacements. To infer the mechanical constitutive laws from these measurements, a finite element (FE) analysis was provided. This analysis aimed at simulating the indentation experiment. An optimization process was used to determine the FE constitutive laws that provided the non-linear force/displacements observed during the indentation experiments. The tongue constitutive law was used for simulations provided by a 3D FE biomechanical model of the human tongue. This dynamical model was designed to study speech production. Given a set of tongue muscular commands, which levels correspond to the force classically measured during speech production, the FE model successfully simulated the main tongue movements observed during speech data.

Unusual association of myasthenia gravis and ulcerative colitis in a 14-year-old boy.

Ulcerative colitis (UC) is a chronic inflammatory condition. Its incidence is 0.8 per 100,000 children per year and median age at diagnosis is 14.1 years in the pediatric population. Extradigestive manifestations are frequent in inflammatory bowel disease (IBD), but neurologic disorders are rarely associated. We report the case of a 14-year-old boy who was diagnosed with UC and thereafter autoimmune hepatitis with primary sclerosing cholangitis. Two months later, he also developed myasthenia gravis, another autoimmune disease. Physicians should be aware of the possibility of an association between several autoimmune diseases in patients with IBD in order to improve disease outcomes.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

Evidence of mitochondrial impairment during cardiac allograft rejection.

NADH laser fluorimetry and mitochondrial oxigraphy were used to study myocardial oxidative energy metabolism during cardiac allograft rejection. Heterotopic cardiac transplantation was performed on Lewis rats; allografts (with Fischer rat donors) were compared with isografts (with Lewis rat donors). In vivo and in vitro assays were performed six days after transplantation. Myocardial NADH fluorescence was recorded in vivo from grafted hearts, at baseline; during brief, complete ischemia; and during reperfusion. Oxygen consumption of mitochondria isolated from both native and grafted hearts was determined. Neither baseline levels nor maximum ischemic levels of NADH fluorescence (F0 = k[NADH]) were found to be significantly different between allografts (0.45 +/- 0.05 to 0.87 +/- 0.10) and isografts (0.45 +/- 0.04 to 1.11 +/- 0.05). During recovery, the rate of fluorescence decrease was significantly lower in allografts than in isografts (0.024 +/- 0.001 vs. 0.038 +/- 0.002 delta F0.s-1, P less than 10(-3], indicating a lower rate of NADH reoxidation. In the presence of malate and glutamate substrates, mitochondrial O2 consumption was significantly lower in allografts than in isografts (30 +/- 9 vs. 100 +/- 15 nanoatoms O2. min-1.mg prot-1, P less than 10(-2]. These results indicate that mitochondrial oxidative metabolism was impaired during the rejection process. Such energy production disturbances may contribute to the dysfunction of rejecting hearts.

Regulation of the chemokine system at the level of chemokine receptor expression and signaling activity.

The chemokine system is highly influenced by the microenvironmental context. Regulation of the chemokine system occurs not only at the level of agonist production, but also at the level of chemokine receptor expression. This review provides examples of regulation of the system at the receptor level by modulation of receptor expression in canonical cellular targets (tuning of the system), and induction of novel receptors (shaping of the system), with particular attention to dendritic cells as a cellular model. Receptor signaling activity represents a further potential level of regulation of the system. Finally, chemokines can also influence the microenvironment by modulating gene expression in target cells.

Quantitative assessment of the effect of some excipients on nitrazepam stability in binary powder mixtures.

The decomposition rate constants, normalized for dilution and relative specific surface effects. Of nitrazepam in simple binary powder mixtures with talcum, lactose-H2O, microcrystalline cellulose, corn starch, mannitol, and saccharose are shown to be linearly related to the nitrogen adsorption energy of the excipients.

Coronary artery restenosis following transluminal coronary angioplasty.

Morphological changes are described in a case of coronary restenosis occurring three and ten months after transluminal coronary angioplasty. The lesions consisted of severe narrowing of the previously mechanically dilated coronary segments. This narrowing was produced by fibrocellular intimal hyperplasia associated with rupture of the media whereas the atheromatous plaque was not involved. This suggests that medial injury associated with healing intimal hyperplasia could be the major factor resulting in late coronary restenosis.

In vivo evaluation of a trileaflet mechanical heart valve.

Design goals for a mechanical heart valve include duplicating the hemodynamic performance of the natural valve, eliminating the need for anticoagulants, and maintaining safety. The Lapeyre-Dassault (Dassault-Aviation, Paris, France) prosthetic valve, undergoing development, addresses these goals. The unique trileaflet design consists of a solid titanium ring and three leaflets. Prototypes of the valve fabricated with Delrin leaflets were implanted in the mitral position in six calves (70-90 kg). Four calves (Studies 1, 2, 3, 5) had long-term survival of 165, 158, 219, and 281 days, respectively. Two calves were killed, one on Day 37 and one on Day 39, after complications unrelated to the valve developed. In all calves heparin was given intravenously to maintain partial thromboplastin time at 1.5 to 2.0 x baseline for approximately 1 week. In Studies 1 and 2 full anticoagulation and antiplatelet therapy was given (orally administered sodium warfarin to maintain prothrombin time at 1.5 to 2.0 x baseline, along with aspirin (1 g/day) and dipyridamole 400 mg/day). In Study 3, all anticoagulation and antiplatelet therapy was discontinued at 1 month after implant. In Study 5, no anticoagulation therapy was given after the initial week of intravenous heparin; however, antiplatelet therapy was started on the fifth postoperative month and maintained until the study's end at 9 months. At 1, 2, 3, and 5 months, the mean plasma free hemoglobin level in the four long-term animals was 5.0 +/- 2.16, 6.0 +/- 3.83, 8.5 +/- 4.93, and 11.3 +/- 6.74 mg/dl, respectively. Hemolysis was not a problem. Valve performance during normal activity was excellent in all the calves, as evidenced by echocardiography and the overall appearance of good health. In the four completed long-term studies, left heart catheterization showed a mean valve pressure gradient of 11.57 +/- 1.26 mmHg and no apparent valvular regurgitation. Histopathologic examination of major organs showed no evidence of thromboembolic events. This study shows that the innovative design of this trileaflet valve performed well in initial in vivo testing, justifying further development.

Variation in anticipatory coarticulation with changes in clarity and rate.

This study tests the hypothesis that the relative timing, or coarticulation, of articulatory movements at VC and CV boundaries is influenced by both the listener's requirement for clarity and the speaker's strategy to economize effort. Movement and acoustic data were collected from 7 subjects who spoke in three conditions: normal, clear, and fast. It was predicted that fast speech would show more coarticulation and clear speech would show less coarticulation than normal speech. The speech materials were designed to investigate coarticulation in the movements of the upper lip and tongue. They consisted of repetitions of [iC(n)u] utterances embedded in carrier phrases, where the number of consonants, n, ranged from 1 to 3. Analyses focused on kinematic measures and the amount of coarticulation (overlap) of the /i-u/ transition movement with the acoustic interval of the /i/. The consonant-string duration was longest in the clear speaking condition and shortest in the fast condition. Compared to the normal condition, peak velocities were higher in the fast and clear speaking conditions, indicating increased effort. The influences of speaking condition on coarticulation and on the formants of the /i/ were small. Thus, even though there was evidence of increased effort in the clear and fast conditions, the hypothesized effects of a trade-off between clarity and economy of effort were minimally evident in formant values for /i/ and measures of coarticulation.

[Reoperations after surgical correction of tetralogy of Fallot]. / Réopérations après correction chirurgicale de tétralogie de Fallot.

Between 1970 and 1981, 40 patients (6%) were reoperated after surgical correction of Fallot's tetralogy. The average age of these patients was 7,5 years (range 2 months to 37 years). The usual anatomical form was present in 30 cases and severe forms accounted for the other 10 cases (pulmonary atresia with septal defect were excluded). The 40 patients were divided into 3 groups according to the anatomical lesions corrected at reoperation: Group I: 16 patients with a residual isolated VSD; Group II: 14 patients with one or two residual right heart anomalies (RRHA) but without a septal defect; Group III: 10 patients with a residual VSD and RRHA. The only clinical difference between the patients of these 3 groups was the delay of onset of symptoms: the patients with residual VSD (Groups I and III) often developed cardiac failure immediately, whilst in those without residual VSD (Group II) cardiac failure was usually observed secondarily. Four patients (10%) died early after reoperation (less than 1 month). Three others died later, two during a third operation. The total mortality was similar in the three groups. The surgical result was assessed clinically after an average follow-up of 4,5 +/- 3 years: patients with a residual isolated VSD (Group I) had the best long-term results. In 12 patients, M mode and 2D echocardiography showed normal left ventricular function but the ratio of end diastolic right ventricular and left ventricular dimensions was increased to an average of 0,72 +/- 0,2.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of skin improvement treatment efficacy using the photograding of mechanically-accentuated macrorelief of thigh skin.

The assessment of the efficacy of skin improvement treatments could be obtained by several different instrumental tests. In parallel to these techniques, a visual evaluation more closely related to the consumer's considerations would be of value for the assessment of slimming treatments efficacy. A method of macrorelief scoring of skin has been developed as an alternative to usual clinical assessment. It consisted of acquiring macroscopic views of the most representative areas of women's cellulite. Photographs were taken after application of a gripping system around the thigh, used to increase the orange peel look of the skin over a restricted area (200 cm(2)) and then classified by observers according to reference groups of cellulite intensity. This publication presents the validation of this photograding method and the results of the first 2-month double-blind placebo-controlled clinical study performed on 30 subjects with this technique associated with: (i) B mode ultrasound imaging in order to correlate scorings with instrumental measurements of thigh adipose tissue thickness variations and (ii) self-evaluation questionnaire aiming at evaluating the overall appraisal and attitude towards the two products. The results clearly showed that the effects of 'slimming products' on the skin's macrorelief improvement could be evaluated objectively using this photograding technique. Moreover, the method described here allows delayed scoring of cellulite intensity from a restricted examination area independent of whole-subject appearance, thus decreasing subjectivity.

[HLA and familial multiple sclerosis]. / HLA et scléroses en plaques familiales.

Some data suggest an environmental perhaps a viral factor but also of a genetic factor in the etiology of multiple sclerosis. Among the latter is the notably increased risk for a twin when the other twin has the disease, a risk further increased if they are monozygotic. There is also a greater than chance frequency of common HLA haplotypes in 2 affected siblings. The frequency of familial forms of multiple sclerosis is estimated at approximately 6 p. 100. We have studied 14 families of which 12 included 2 members with multiple sclerosis and 2 with 3 affected members. Parental relation between patients was parent to child (7 cases), brother to sister (5 cases), sister to sister including two pairs of twins (4 cases) and cousin to cousin on the mother's side (2 cases). When compared with non-familial multiple sclerosis there were no particular features in clinical disorders or course: 4 forms were progressive, the others evolving by episodes. In 26 patients in whom HLA antigens were determined, the DR2 antigen was present 19 times, the B7 antigen 9 times and the A3 antigen 7 times. In the 8 pairs of siblings with multiple sclerosis, 2 were HLA-identical and 5 semi-identical. One pair had no common haplotype. Grouping of HLA in 22 healthy members allowed 8 genealogic trees to be established. If a gene for susceptibility to multiple sclerosis exists, it is of low penetration, of dominant transmission and of limited frequency. It probably lies close to the region D of chromosome 6, because of the disequilibrium of crossed linking with A3, B7 and DR2 antigens.

[Association of sarcoidosis and hemorrhagic rectocolitis in an insulin-dependent diabetic]. / Association d'une sarcoïdose et d'une rectocolite hémorragique chez un diabétique insulino-dépendant.

Ulcerative colitis and sarcoidosis are seldom associated. A 33-year-old diabetic man developed simultaneously a rectitis and a non-productive cough leading to the diagnosis of ulcerative colitis and sarcoidosis. These diagnoses are discussed because of the possible gastrointestinal lesions from sarcoidosis or the respiratory disorders due to ulcerative colitis. Some pathophysiological evidence can be found in this case in favor of a non-fortuitous association.

[Population genetics, immunologic evaluation and Buerger's disease. Projection through a personal study comprising 127 cases of juvenile arteriopathy]. / Génétique des populations, bilan immunitaire et maladie de Buerger. Projection à travers une étude personnelle regroupant 127 cas d'artériopathies juvéniles.

The analysis of anamnestic, clinical and arteriographic parameters in 127 young patients with arterial disease of the lower limbs allowed a definite distinction between thromboangiitis obliterans (TAO) and early-onset atheroma, even if the etiopathogenic of TAO is still obscure. The HLA gene frequency has been determined in 54 patients (14 TAO, 40 early atheroma) and has been compared with local blood donors and with caucased subjects from the IXth Workshop. The results (higher frequency of HLA A28, AX, B53 and BX in the TAO group) have, however, a dubious significance. Furthermore, there were no differences between TAO and early atheroma in a comparative study of immunological parameters (anti-nuclear antibodies, circulating immune complexes, C3, C4 and CH50, cryoglobulin) in 72 patients (22 TAO, 50 early atheroma). So, neither a genetic predisposition nor a dysimmunity could be involved in the pathogenesis of TAO.