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Near normal glycaemic control in diabetes consists to target daily glucose fluctuations and quarterly HbA1c oscillations in addition to overall glucose exposure. Consequently, the prerequisite is to define simple, and mathematically undisputable key metrics for the short- and long-term variability in glucose homeostasis. As the standard deviations (SD) of either glucose or HbA1c are dependent on their means, the coefficient of variation (CV = SD/mean) should be applied instead as it that avoids the correlation between the SD and mean values. A CV glucose of 36% is the most appropriate threshold between those with stable versus labile glucose homeostasis. However, when near normal mean glucose concentrations are achieved a lower CV threshold of <27 % is necessary for reducing the risk for hypoglycaemia to a minimal rate. For the long-term variability in glucose homeostasis, a CV HbA1c < 5 % seems to be a relevant recommendation for preventing adverse clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is a highly prevalent health condition in the aging population. Older adults with T2DM have higher risks of cardiovascular disease, heart failure (long underestimated) and premature death than those without diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven their ability to improve cardiovascular prognosis and reduce the risk of hospitalization for heart failure (hHF). However, several adverse events have been reported, whose incidence and severity might be increased in the elderly population. The aims of this comprehensive review were to analyze the benefit-risk ratio of SGLT2i therapy in older patients with T2DM by collecting data from (i) large prospective placebo-controlled cardiovascular outcome trials (including those dedicated to heart failure), using both original publications and dedicated post-hoc analyses across different age groups and (ii) observational cohort studies, describing the effects of SGLT2is versus other glucose-lowering agents on cardiovascular outcomes and hHF in elderly patients or these effects in different age groups. Overall, consistent results showed a similar relative risk reduction in cardiovascular mortality and hHF with SGLT2is independently of age. The absolute risk reduction may be greater in elderly because of a higher background risk in older versus younger patients. Similarly, the safety profile of SGLT2is appeared comparable in older versus younger patients. In conclusion, the benefit/risk balance favors the use of SGLT2is in older patients at risk of cardiovascular disease and/or heart failure. Caution may be required in very old frail patients, especially those exposed to an increased risk of volume depletion., (Copyright © 2023. Published by Elsevier Masson SAS.)

Objectives: The behavioral summarized evaluation scales, the BSE and its revised version the BSE-R, were developed and validated in the 1980-1990s. The BSE-R is still used daily by clinical teams in France and foreign countries, and it is recommended by the French Health Authority (2018). Having taken into account knowledge improvement in neurodevelopment and autism spectrum disorder (ASD) and the importance of observation by relatives in ecological context, the second version of the BSE was developed. This paper presents the construction and the validation study of the second version of the behavioral summarized evaluation scale, the BSE2 and the BSE2-P rated by parents., Methods: Construct validity of the BSE2 scale has been studied in a population of 244 children and adolescents with ASD according to DSM-5 criteria, aged from 30 months to 18 years. Discriminant validity has been analyzed using a population of 86 patients of the same age, with neurodevelopmental disorder (NDD) without comorbidity of ASD., Results: BSE2 comprises 30 items and is a two-dimensional scale as was BSE-R. Both dimensions, labelled "Interaction" (11 items) and "Modulation" (11 items), accounted for 41.7 % of the total variance. They describe autism severity and are in accordance with the two DSM-5 dimensions. Internal consistency (0.927 and 0.850 respectively) and inter-rater reliability (0.932 and 0.897 respectively) are good or excellent for both dimensions. Sensibility and specificity (0.758 and 0.767 respectively) range BSE2 among the tools with good psychometric properties. The parent version, BSE2-P, dedicated to ecological context is easily rated by parents., Conclusions: BSE2 scale for children and adolescents is a clinical tool with good psychometric properties. Its two-dimensional structure is in accordance with DSM-5 criteria. This scale covers all spectrum of ASD clinical forms in both children and adolescents. It can be used to identify ASD in complex neurodevelopmental disorders with several comorbidities and can help to distinguish autism symptomatology from other neurodevelopmental diagnoses. Furthermore, this scale allows to expand the rating context, involving parents to define and adjust the individualized therapeutic project. Thus the BSE2 is a valuable clinical tool for practitioners for both diagnosis and follow-up., (Copyright © 2021 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Adaptation to the sensory environment is essential in everyday life, to anticipate future events and quickly detect and respond to changes; and to distinguish vocal variations in congeners, for communication. The aim of the current study was to explore the effects of the nature (vocal/non-vocal) of the information to be encoded, on the establishment of auditory regularities. In electrophysiology, neural adaptation is measured by the 'Repetition Positivity' (RP), which refers to an increase in positive potential, with the increasing number of repetitions of a same stimulus. The RP results from the combined variation of several ERP components; the P1, the first positivity (∼100 ms) may reflect the onset of repetition effects. We recorded auditory evoked potentials during a roving paradigm in which trains of 4, 8 or 16 repetitions of the same stimulus were presented. Sequences of vocal and non-vocal complex stimuli were delivered, to study the influence of the type of stimulation on the characteristics of the brain responses. The P1 to each train length, and the RP responses were recorded between 90 and 200 ms, reflecting adaptation for both vocal and non-vocal stimuli. RP was not different between vocal and non-vocal sequences (in latency, amplitude and spatial organization) and was found to be similar to that found in previous studies using pure tones, suggesting that the repetition suppression phenomena is somehow independent of the nature of the stimulus. However, results showed faster stabilization of the P1 amplitude for non-vocal stimuli than for vocal stimuli, which require more repetitions. This revealed different dynamics for the establishment of regularity encoding for non-vocal and vocal stimuli, indicating that the richness of vocal sounds may require further processing before full neural adaptation occurs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

After years of intensive investigation, the definition of glycaemic variability remains unclear and the term variability in glucose homoeostasis might be more appropriate covering both short and long-term glycaemic variability. For the latter, we remain in the search of an accurate definition and related targets. Recent work leads us to consider that the within-subject variability of HbA1c calculated from consecutive determinations of HbA1c at regular time-intervals could be the most relevant index for assessing the long-term variability with a threshold value of 5% (%CV = SD of HbA1c/mean HbA1c) to separate stability from lability of HbA1c. Presently, no one can deny that short- and long-term glucose variability should be maintained within their lower ranges to limit the incidence of hypoglycaemia. Usually, therapeutic strategies aimed at reducing post-meal glucose excursions, i.e. the major contributor to daily glucose fluctuations, exert a beneficial effect on the short-term glucose variability. This explains the effectiveness of adjunct therapies with either GLP- receptor agonists or SGLT inhibitors in type 2 diabetes. In type 1 diabetes, the application of a CGM device alone reduces the short-term glycaemic variability. In contrast, sophisticated insulin delivery does not necessarily lead to such reductions despite marked downward shifts of 24-hour glycaemic profiles. Such contrasting observations raise the question as to whether the prolonged wear of CGM devices is or not the major causative factor for improvement in glucose variability among intensively insulin-treated persons with type 1 diabetes., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Restricted-calorie diets are the most worldwide used treatments for obesity. Although such strategies are based on the first law of thermodynamics, the real life clinical practice demonstrates that the observed weight losses are divergent from those theoretically predicted. Loosely adherence to recommendations is one of the main causes for the limited efficacy of dieting, but many additional factors can be involved in the hurdles to weight loss. According to the second law of thermodynamics any restriction in dietary energy intake results in energy sparing with a diminution in the basal metabolic rate and a concomitant loss in the lean body mass. This "thrifty" energetic adaptation is associated with a progressive reduction in the difference between levels of energy intake and expenditure, thus resulting in a drastic fall in weight loss rates on the medium and long-term regardless of the dietary carbohydrate/fat ratio. This loss of efficacy is aggravated by the misadaptation of the production and action of anti-obesity hormones such as leptin. During the latest past decades the discovery of changes in the gut microbiota of obese people referred to as "obese dysbiosis" has raised the question as to whether these alterations can participate to diet-resistance. Combined with the behavioral and psychological barriers to low-calorie diets, there is a broad physiologic spectrum of evidence indicating that weight loss is a hard challenge. Consequently, the answer would be primarily to prevent the development of obesity and at worst to avoid its ominous progression from metabolically healthy to unhealthy stages., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aim: Plasma levels of certain ceramides are increased in patients with ischemic heart disease (IHD). Many risk factors for IHD are also risk factors for chronic kidney disease (CKD), but it is currently uncertain whether plasma ceramide levels are increased in patients with CKD., Methods: We measured six previously identified high-risk plasma ceramide concentrations [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] in 415 middle-aged individuals who attended our clinical Cardiology and Diabetes services over a period of 9 months., Results: A total of 97 patients had CKD (defined as e-GFR CKD-EPI <60ml/min/1.73m 2 and/or urinary albumin-to-creatinine ratio≥30mg/g), 117 had established IHD and 242 had type 2 diabetes. Patients with CKD had significantly (P=0.005 or less) higher levels of plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) compared to those without CKD. The presence of CKD remained significantly associated with higher levels of plasma ceramides (standardized beta coefficients ranging from 0.124 to 0.227, P<0.001) even after adjustment for body mass index, smoking, hypertension, diabetes, prior IHD, plasma LDL-cholesterol, hs-C-reactive protein levels and use of any lipid-lowering medications. Notably, more advanced stages of CKD and abnormal albuminuria were both associated (independently of each other) with increased levels of plasma ceramides. These results were consistent in all subgroups considered, including patients with and without established IHD or those with and without diabetes., Conclusion: Increased levels of plasma ceramides are associated with CKD independently of pre-existing IHD, diabetes and other established cardiovascular risk factors., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aim: Emerging evidence suggests that specific plasma ceramides are involved in the pathophysiology of cardiovascular disease (CVD) and other inflammation-associated diseases. However, scarce information is currently available on the association between distinct plasma ceramides (that have been associated with increased cardiovascular morbidity and mortality) and plasma high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with type 2 diabetes mellitus (T2DM), a group of individuals at high risk of developing CVD and other chronic inflammation-related conditions., Methods: We measured six previously identified high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] in 92 postmenopausal women with T2DM attending the diabetes outpatient service over a 3-month period. Plasma ceramide levels were measured using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay., Results: Plasma hs-CRP levels were positively associated with all measured ceramides in univariable linear regression analyses. However, only plasma Cer(d18:1/16:0) (standard β coefficient: 0.27, P=0.015), Cer(d18:1/22:0) (standard β coefficient: 0.25, P=0.032) and Cer(d18:1/24:1) (standard β coefficient: 0.30, P=0.007) remained significantly associated with increased plasma hs-CRP levels after adjusting for age, adiposity measures, diabetes duration, HbA 1c , insulin resistance, smoking, hypertension, plasma LDL cholesterol, estimated glomerular filtration rate, preexisting ischaemic heart disease and use of lipid-lowering, antihypertensive, antiplatelet or hypoglycaemic drugs., Conclusion: In postmenopausal women with T2DM, elevated levels of specific plasma ceramides are associated with higher plasma hs-CRP levels independent of established cardiovascular risk factors, diabetes-related variables and other potential confounding factors., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Aim: Recent prospective studies have identified distinct plasma ceramides as strong predictors of major adverse cardiovascular events in patients with established or suspected coronary artery disease (CAD). Currently, it is uncertain whether higher levels of distinct plasma ceramides are associated with greater angiographic severity of coronary-artery stenoses in this patient population., Methods: We measured six previously identified high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD, who underwent urgent or elective coronary angiography., Results: Approximately 77% of patients had a significant stenosis (≥50%) in one or more of the main coronary arteries, the majority of whom (∼60%) had a significant stenosis in the left anterior descending (LAD) artery. Of the six measured plasma ceramides, higher levels of plasma Cer(d18:1/20:0) (adjusted-odds ratio 1.39, 95%CI 1.0-1.99), Cer(d18:1/22:0) (adjusted-odds ratio 1.57, 95%CI 1.08-2.29) and Cer(d18:1/24:0) (adjusted-odds ratio 1.59, 95%CI 1.08-2.32) were significantly associated with the presence of LAD stenosis≥50%, after adjustment for age, sex, smoking, pre-existing CAD, hypertension, diabetes, dyslipidaemia, lipid-lowering therapy, estimated glomerular filtration rate and plasma C-reactive protein levels. Almost identical results were found even after excluding patients (n=15) with acute ST-elevation myocardial infarction. Similar results were also found when patients were categorized according to the Gensini severity score., Conclusion: Our cross-sectional study shows for the first time that higher levels of specific plasma ceramides are independently associated with a greater severity of coronary-artery stenoses in the LAD artery in patients who had suspected or established CAD., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Introduction: Prevalence of postpartum depression (PPD) ranges from 10 to 15 % of parturients. The impact of the PPD is major on the maternal bond and the health of both mother and child. Its physiopathological mechanisms appear to differ from other types of depression. Today, pharmacotherapy is based on nonspecific treatment, and recent therapeutic advances in this field require a comprehensive approach of the implication of the GABAergic system in the development of PPD. Neurosteroid levels during pregnancy and after parturition and the GABA-A-r modulation are thought to be involved in PPD., Objective: To evaluate if the GABAergic approach is relevant in postpartum depression management., Methods: We conducted a systematic review of literature based on the MEDLINE database with the following Medical Subject Headings (MeSH): "postpartum depression", "GABA", "ganaxolone", "brexanolone", "allopregnanolone", prior to September 2019. We selected articles in English: preclinical and clinical studies, literature review, observational and therapeutic studies., Results: Preclinical models (mouse and rat) show changes in GABAergic inhibition in the peripartum period and correlation between allopregnanolone and GABA-A-r plasticity. This plasticity in the peripartum period maintains levels of inhibition adapted despite increased neurosteroid levels. KO models for the GABA-A-r δ subunit develop depression and anxiety symptoms in the postpartum period, and a change in the expression of the gene coding for the GABA-R alpha-4 subunit was found. Artificial inhibition of progesterone metabolism during post-partum increased depression symptoms. GABAergic fluctuation seems to be interrelated with other systems such as those of oxytocins. A synthetic neurosteroid (SGE-516) was tested on mouse models of PPD, KO for δ-GABA-A-r or KCC2, and showed decreased depressive symptoms and better mothering. Clinical studies confirm neurosteroid fluctuation and changes in the GABAergic system during the peripartum period. Allopregnanolone is the neurosteroid the most studied in PPD, and it is elevated in the brain during the pregnancy. Studies disagree on the presence of significant differences in allopregnanolone plasma levels during pregnancy or postpartum between women with PPD or not. Women with a history of PPD have greater susceptibility to neurosteroid withdrawal. Imagery and genetical data also show a link between allopregnanolone and PPD. The GABA-A-r may not recover in time following a reduced number during pregnancy, and this mismatch between neurosteroid levels and their receptor may trigger PPD. Several randomized controlled trials investigated brexanolone administrated IV, a synthetic formulation of allopregnanolone, and demonstrated a rapid and well tolerated reduction in depressive symptoms. In March 2019 brexanolone obtained FDA approval in PPD indication under the name Zulresso. However, there are differences in the time of beginning of PPD, which could constitute different subgroups of this disease, and which physiopathology could respond to different mechanisms. Prenatal depression does not respond to a GABAergic approach, but women without any risk factor or previous mood disorder developing PPD in the weeks following childbirth could be particularly responsive to this kind of treatment., Conclusion: Disability to modulate GABA-A-r expression during pregnancy and restore its previous state after parturition appears to trigger PPD. The GABAergic system is a promising pharmacotherapy target. From preclinical to clinical studies for about twenty years the GABAergic system has been incriminated and targeted in this challenging mental disease., (Copyright © 2019 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Psychomotor impairments in Autism Spectrum Disorders (ASD) have frequently been described in scientific literature. Such deficits impact upon the development of social motor function and interfere with the ability to adjust to everyday life. The inclusion of sensory-motor signs in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirms their importance in the diagnosis of ASD. Previous literature has shown the presence precocity of these signs, sometimes before the alteration of the social communication. To our knowledge, there are no existing clinical tools to measure sensory-psychomotor deficit, specifically in ASD. The current paper presents the construction and validation of a new scale, designed to evaluate sensory-psychomotor signs in Autism: 'the Sensory-psychomotor Particularities Scale in Autism' (SPSA)., Method: The scale is composed of 160 items describing common sensory-psychomotor signs in autism. These items are grouped into 20 variables: touch, nociception, vestibular sensitivity, proprioceptive sensitivity, vision, auditory, multimodality, tone, posture, balance, global coordination, manual dexterity, body schema, bodily self-consciousness, relational adjustment, emotional expression, use of objects, space, time and tonico-emotional regulation. For each item, the psychomotor therapist evaluated sensori-psychomotor signs according to a five-level Likert scale (0="the sign is never expressed by the person", 1="weakly expressed", 2="moderately expressed", 3="severely expressed" and 4="the sign is very characteristic of the person and very severely expressed"). This is completed by a family interview in order to assess the impact of these signs on everyday situations. The study included 111 children with autism. The presence of neurological and genetic diseases was exclusion criteria. For each child, a global developmental evaluation was carried out by an expert clinical team specializing in ASD. Standardized clinical tools were used: Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Behavior Summarized Evaluation scale (BSE-R), Repeated and Restricted Behavior scale (RRB), Movement Assessment Battery for Children (M-ABC), Motor Development Rating scale (MDR), Sensory Profile (SP). Developmental quotients (DQ) were evaluated using various tests depending on age and ability., Results: Factor analysis produced three clinically relevant factors: F1: "sensory-emotional synchronization", F2: "multisensory integration" and F3: "motor skills": each containing a similar quantity of items. They account for roughly equal percentages of variance (18.9%, 18.0%, 16.8%, respectively). The factorial structure does not change if the 26 children with comorbid developmental coordination disorder are removed. The three factors show good internal consistency and excellent inter-rater reliability. F1 is comprised of 6 items: touch, nociception, proprioceptive sensitivity, vision, emotional expression and tonico-emotional regulation. This factor is significantly associated with items of the Sensory Profile (touch processing, poor registration, sensory seeking). F2 is comprised of 5 items: multimodality, bodily self-consciousness, relational adjustment, use of objects and space. This factor is associated with ADOS, BSE-R and RRB scores, and the item "touch processing" of the Sensory Profile. F3 is comprised of 4 items: tone, posture, global coordination, manual dexterity. This factor is associated with the M-ABC, the MDR and the item "low endurance" of the Sensory Profile., Conclusion: The SPSA is a relevant clinical tool to assess the severity of sensory-psychomotor clinical signs in order to describe the individual profiles of children with ASD. It represents a critical step in advancing knowledge of the complex and heterogeneous pattern of psychomotor development in autism. It could make a valuable contribution to the field, both in research and clinical practice., (Copyright © 2019 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Chronic low-grade inflammation is a recognized key feature associated with type 2 diabetes mellitus (T2DM) and its complications. In prospective randomized trials, sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated benefits related to several cardiovascular and renal risk factors, including HbA 1c , blood pressure, body weight, renal hyperfiltration, and improvement of cardiorenal outcomes. SGLT2 inhibitors may improve adipose tissue function and induce decreases in serum leptin, TNF-α and IL-6 while increasing adiponectin. While data on high-sensitivity C-reactive protein and other inflammatory markers are relatively scarce in humans, in animals, a number of reports have shown reductions in cytokine and chemokine concentrations in parallel with protective effects against progression of atherosclerotic lesions. Experimental findings also suggest that part of the renoprotective effects of SGLT2 inhibition may be related to anti-inflammatory actions at the kidney level. Underlying mechanisms to explain this anti-inflammatory effect are multiple, but may involve weight loss, and reduction in adipose tissue inflammation, slight increase in ketone bodies and diminution of uric acid levels or attenuation of oxidative stress. However, further studies in diabetes patients with specific assessment of inflammatory markers are still necessary to determine the specific contribution of the anti-inflammatory action of SGLT2 inhibitors to the reduction of cardiovascular and renal complications and mortality observed with this class of antidiabetic drugs., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the K ATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs. various comparators as both mono- and combination therapy. Pioglitazone can prevent recurrence of stroke in patients with previous stroke, as already shown in PROactive, although results are less clear for first strokes. As for DPP-4 inhibitors, there was a non-significant trend towards benefit for stroke, whereas a possible increased risk of stroke with SGLT2 inhibitors-and in particular, empagliflozin in the EMPA-REG OUTCOME trial-has been suggested and requires clarification. Experimental results support a potential protective effect of GLP-1 receptor agonists against stroke that has, at least in part, been translated to clinical benefits in T2D patients in the LEADER and SUSTAIN-6 trials. Further interventional studies are now warranted to confirm the effects of glucose-lowering agents on risk of stroke in patients with T2D. In summary, the effects of antidiabetic drugs on risk of stroke appear to be heterogeneous, with some therapies (pioglitazone, GLP-1 receptor agonists) conferring possible protection against ischaemic stroke, other classes showing a neutral impact (DPP-4 inhibitors, insulin) and some glucose-lowering agents being associated with an increased risk of stroke (sulphonylureas, possibly SGLT2 inhibitors, high-dose insulin in the presence of insulin resistance)., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Interstitial lung disease, cutaneous rash and elevated serum angiotensin converting enzyme (ACE) may suggest diagnoses other than sarcoidosis., Patients and Methods: A 58-year-old man had presented dyspnoea for 2 years with increased angiotensin-converting enzyme, as well as an interstitial syndrome and micronodules. The possibility of sarcoidosis was raised. Systemic corticosteroids resulted in improvement of the dyspnoea although it recurred on dose reduction. We noted fluctuating eczematous macules of the limbs with a histology of aspecific folliculitis. The identification of Mycobacterium avium complex (MAC) in the bronchoalveolar wash prompted us to initiate antimycobacterial therapy, but this was to no avail. Review of the CT-scan and questioning of the patient (daily use of a Jacuzzi for 7 years) resulted in diagnosis of hypersensitivity pneumonitis due to MAC. The cutaneous lesions were taken to indicate "hot tub folliculitis". Discontinuation of hot-tub use and a short course of oral corticosteroids resulted in healing within 4 months, with no recurrence at 2 years., Discussion: HTL is a form of hypersensitivity pneumonitis due to the presence of MAC in the water of Jacuzzis. This condition regresses spontaneously without treatment on discontinuation of Jacuzzi use. Hot-tub folliculitis due to Pseudomonas aeruginosa (PA) presents as macules and papules on covered skin areas (swimsuit) within 48hours of bathing and often declines within 2 weeks., Conclusion: Our case is original as regards the concomitant lung and cutaneous involvement associated with Jacuzzi use, with an immunoallergic mechanism for the MAC and probably an infectious mechanism for the PA., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Aim: Adiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population., Methods: Two polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n=5212) and people with T2D in the DIABHYCAR study (n=3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n=230), and in controls who remained normoglycaemic (n=226) throughout., Results: In a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04-1.18; P=0.001) and 0.92 (95% CI: 0.87-0.98; P=0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P=0.03) and HbA 1c (P=0.006), and lower plasma adiponectin levels (P=0.03) in the D.E.S.I.R., Participants: Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P=0.03), HbA 1c (P=0.02) and Fatty Liver Index (FLI; P≤0.01), and higher plasma adiponectin levels (P=0.002). Associations with HbA 1c , FLI and adiponectin levels persisted after adjusting for BMI., Conclusion: CDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: Functional gastrointestinal disorders (FGID) such as diarrhoea and constipation can reflect intestinal dysfunction, especially with regard to intestinal microbiota, which, in turn, have been associated with chronic conditions, including obesity and insulin resistance. However, little is known of the association between FGID and type 2 diabetes (T2D) risk., Design and Methods: This analysis aimed to determine the influence of diarrhoea, constipation and alternating bouts of diarrhoea/constipation on T2D risk in 62,683 women from the prospective E3N-EPIC cohort., Results: A total of 1795 T2D cases were recorded during follow-up. Compared with women who had normal gastrointestinal transits, women with chronic diarrhoea or alternating diarrhoea/constipation were at increased risk of T2D (HR: 1.29, 95% CI: 1.00-1.65 vs. HR: 1.32, 95% CI: 1.15-1.52, respectively), whereas women with constipation had a decreased risk (HR: 0.67, 95% CI: 0.57-0.78). There was no interaction between FGID and body mass index for risk of T2D. Also, these associations were independent of dietary habits such as coffee, fruit and vegetable consumption, and even of the use of laxatives and psychotropic drugs., Conclusion: The present analysis showed, for the first time, a limited association between FGID and T2D risk in a large prospective cohort, and supports the hypothesis of a relationship between gastrointestinal function and diabetes. The presence of gastrointestinal transit disorders may assist in screening for subjects at higher risk of diabetes beyond the conventional risk factors., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Orbital tumors are a rather frequent pathology. Their diagnosis and treatment may be difficult. They can be benign or malignant. All the tissues of the orbit can give rise to a tumor, resulting in their large number. Among the benign tumors, we have meningiomas and cavernous hemangiomas, and for the malignant tumors, lymphomas, metastasis, ENT tumors and lacrimal gland tumors in the adult. Usually the signs are nonspecific, with proptosis, oculomotor disturbance, inflammatory signs, pain and sometimes a mass. Imaging (CT, MRI and color Doppler ultrasound) shows the tumor, its location, extent and possible metastases. Biopsy and anatomic and cytopathologic examination confirm the type of benign or malignant tumor. Based on these three elements: clinical appearance, imaging and histology, the tumor will be treated, usually by a surgical approach according to the recommendations of a multidisciplinary tumor conference. Radiation therapy and chemotherapy may supplement the treatment., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Aim: The aim of this study was to assess interactions between glucose and iron homoeostasis in the adipose tissue (AT) of obese subjects., Methods: A total of 46 obese patients eligible for bariatric surgery were recruited into the study. Anthropometric and biochemical characteristics were assessed, and biopsies of subcutaneous (SCAT) and visceral adipose tissue (VAT) performed. The mRNA levels of genes involved in iron and glucose homoeostasis were measured in their AT and compared with a pool of control samples., Results: Gene expression of hepcidin (HAMP) was significantly increased in the SCAT and VAT of obese patients, while transferrin receptor (TFRC) expression was reduced, compared with non-obese controls, suggesting a higher iron load in obese patients. Also, mRNA levels of adiponectin (ADIPOQ) were decreased in both SCAT and VAT in obese patients, and correlated negatively with hepcidin expression, while adiponectin expression was positively correlated with TFRC expression in both SCAT and VAT. Interestingly, TFRC expression in VAT correlated negatively with several metabolic parameters, such as fasting blood glucose and LDL cholesterol., Conclusion: Iron content appears to be increased in the SCAT and VAT of obese patients, and negatively correlated with adiponectin expression, which could be contributing to insulin resistance and the metabolic complications of obesity., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Aim: Patients with diabetes are at greater risk of cardiovascular events. Insulin resistance (IR) and hyperinsulinaemia are both related to an increased cardiovascular risk, but whether IR predicts coronary heart disease (CHD) independently of other risk factors in patients with type 2 diabetes (T2D) is a topic of considerable controversy. The aim of the present study was to evaluate the prospective relationship of fasting insulin, HOMA-IR, fasting plasma glucose (FPG) and 2-h post-load glucose (2hPG) load with CHD incidence among such patients., Methods: A total of 2607 patients with T2D were enrolled in a community-dwelling cohort and followed for an average of 7.2 years. Conventional CHD risk factors, FPG, 2hPG, fasting insulin levels and HOMA-IR index were measured at baseline. Cox regression hazard ratios (HRs) were used to assess CHD risk., Results: A total of 299 'hard' CHD events were registered (in 114 women and 185 men). Increasing levels of fasting insulinaemia were positively associated with CHD incidence. This correlation persisted after controlling for gender, body mass index, blood pressure, lipid profile, medication use and HbA1c [HR for each increase in quartile (fully adjusted model): 1.18 (95% CI: 1.06-1.32); P<0.01]. 2hPG showed a non-linear association with incident CHD [HR of highest vs lowest quartile: 1.64 (95% CI: 1.03-2.61)]. Fasting glycaemia was not associated with CHD risk, whereas HOMA-IR had a direct and independent correlation with CHD risk [HR for each one-quartile increase: 1.19 (95% CI: 1.07-1.34); P<0.01]., Conclusion: Fasting insulin levels are positively associated with incidence of CHD in T2D. Furthermore, 2hPG appears to be a significant predictor of incident CHD independently of other risk factors, including HbA1c. These findings suggest that strategies targeting the reduction of insulinaemia and post-load glycaemia may be useful for preventing cardiovascular complications., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: Teenagers and adults with intellectual disabilities are nowadays "over-handicapped", often due to lack of care in self-sufficiency and continued learning, two essential domains for living in a community. Their cognitive limits, particularly on the executive functions, could be an obstacle to their involvement in the daily life activities, through their difficulties to plan, anticipate, shift and maintain information in working memory. These high level mental functions can be taught with the CRT program (Cognitive Remediation Therapy - Wykes and Reader 2005) developed in other pathologies and providing an adaptation regarding the developmental level of the person., Methods: Firstly, it is essential to determine cognitive developmental levels of the teenager or the adult, using standard tools, such as Wechsler scales. Secondly, functional and/or adaptative levels have to be assessed using specific tools, such as the Vineland Adaptative Behavior Scale 2nd Edition (VABS-II, Sparrow et al., 2005) and the Functional Intervention Scale (EFI, Willaye et al., 2005). Finally, in order to clearly distinguish what are the preserved and impaired cognitive domains, standard tools assessing executive functions such as the Wisconsin Card Sorting Test, the Tower of London, Stroop Test and BADS are used if possible for the patient. The setting of cognitive remediation programs, previously developed for schizophrenic patients, requires adaptation for teenagers and adults with intellectual disabilities, taking into account the limitation of their cognitive abilities. In this paper, we will show that the CRT method for cognitive remediation is particularly relevant for subjects with intellectual disabilities. This method is hence focused on strategies and exercises to improve working memory, categorization and moreover executive functions. Of course this method might need adaptations, with examples based on simplification of the different tasks, notably for verbal materials, and with variations of the media used. These sessions will be part of a wider individualized caring project, allowing the person to transfer the cognitive acquisitions to his/her daily life., Conclusion: The use of cognitive programs adapted to people with intellectual disabilities can provide benefits in the development of autonomy and daily life activities, leading to a better quality of life and self-esteem., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Abstinence from eating and drinking from dawn to sunset characterizes the holy month of Ramadan. For the 50 million Muslims worldwide with diabetes who adhere to this religious fast, the practice results in marked changes in glucose homoeostasis. The sunset meal (Iftar) that breaks the fasting state is followed by exaggerated surges in blood glucose and sustained overnight hyperglycaemia in cases of nocturnal overfeeding. The predawn meal (Suhoor) frequently results in prolonged glucose decay over the daylight hours. These glycaemic disturbances are particularly marked in insulin-treated patients, in those with unsatisfactory diabetes control during the pre-Ramadan period and in patients who are poorly compliant with lifestyle recommendations. Whether such patients should be exempt from the Islamic fast remains an open debate, which might be partially resolved by long-term controlled studies using the technology of continuous glucose monitoring in large populations of patients with diabetes., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Aim: The prevalence and risk factors associated with symptoms of anxiety and depression were determined in African people with diabetes., Methods: This cross-sectional study involved 491 outpatients with type 2 diabetes (T2D) recruited from four diabetes clinics (Conakry, Labé, Boké and Kankan) in Guinea. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate symptoms of anxiety and depression. Logistic regression analysis stratified by gender was performed to identify the associated risk factors., Results: Anxiety and depression symptoms were present in 58.7% and 34.4%, respectively, of the 491 patients with T2D (62.7% women, mean±SD age: 57.9±10.2years). Odds ratios (95% CI) of risk factors independently associated with anxiety were urban residence [2.98 (1.81-4.89)] in women, and low socioeconomic status [0.19 (0.05-0.70)] and HbA1c≥9.0% [2.61 (1.0-6.39)] in men. Factors associated with depression were urban residence [2.13 (1.27-3.58)], older age [1.03 (1.01-1.06)], low socioeconomic status [2.21 (1.34-3.66)] and no previous measurement of HbA1c [12.45 (1.54-100.34)] in women, and insulin therapy [2.28 (1.05-4.92)] and HbA1c≥9.0% [3.85 (1.02-14.48)] in men., Conclusion: Anxiety and depression symptoms in people with type T2D are common in Guinea. Urban residence, low socioeconomic status and high levels of HbA1c were significantly associated with a greater risk of anxiety and depression, highlighting the psychological burden related to diabetes in Africa., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

For millennia, the syndrome that has become known as diabetes was considered to be primarily a disease of the urinary system and, by association, of dysfunction in the kidneys (recognized as the source of urine). In the last decade, there has been renewed interest in the role of the kidneys in the development and maintenance of high glucose levels. This has led to the development of novel agents to inhibit sodiumglucose cotransporter 2 (SGLT-2) as a means to control glucose levels and augment calorie-wasting leading to weight loss. However, beyond actions on glycaemic control, inhibition of proximal glucose absorption via SGLT-2 has significant direct effects to attenuate hyperfiltration and reduce renal hypertrophy. Increased distal sodium delivery may also act to suppress the intrarenal renin-angiotensin-aldosterone system, although systemic activity may be modestly increased due to osmotic diuresis. Reducing proximal glucose reabsorption may also protect the tubular cells from exposure to excess glucose and glucose-induced reactive oxygen species. On the other hand, distal glucose delivery following inhibition of SGLT-2 may increase glycogen deposition, the significance of which is unclear. However, subjects with familial glycosuria appear to have a benign renal prognosis. Some studies have demonstrated significant reductions in albumin excretion in various experimental models and as post-hoc observations in clinical trials. Whether these reflect renoprotection or are simply the result of intraglomerular haemodynamic changes remains unclear. Although promising, such actions remain to be established by comprehensive clinical trials with a renal focus, many of which are currently in progress., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimalizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180mg/dL (10.0mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140mg/dL (7.77mmol/L) during follow-up. The recommended blood glucose target is 140-180mg/dL (7.7-10mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c)≥8%) or severe/repeated hypoglycaemia., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aim: The prevalence of diabetes in the French West Indies is three times higher than in mainland France. We aimed to assess the associations between vitamin D deficiency, vitamin D receptor (VDR) gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes (T2D)., Methods: In this cross-sectional study of 277 patients, 25-hydroxyvitamin D was measured by radioimmunoassay. FokI, BsmI, ApaI and TaqI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. Analysis of covariance and logistic regression were performed., Results: The study included 76 patients of Indian descent and 201 patients of African descent. The prevalence of vitamin D deficiency (<20 ng/mL) was 42.6%. When patients were classified into groups with (G1) and without (G2) vitamin D deficiency, there were no significant differences in age, systolic blood pressure, low-density lipoprotein cholesterol and HbA(1c), although body mass index was significantly higher in G1. Vitamin D deficiency was significantly associated with increased diastolic blood pressure and triglyceride levels, and reduced high-density lipoprotein cholesterol (P<0.05). Prevalence of vitamin D deficiency was decreased in patients carrying the f allele of FokI (OR: 0.52; P=0.02) and the aa genotype of ApaI (OR: 0.46; P=0.05). BsmI and TaqI SNPs were not associated with vitamin D deficiency., Conclusion: The rate of vitamin D deficiency was high in our T2D patients, and was associated with the VDR gene FokI and ApaI polymorphisms and cardiovascular risk profile. Measurements of vitamin D may help to detect T2D patients with cardiovascular risk, and VDR polymorphisms might explain why vitamin D deficiency is so frequently seen in some T2D patients., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Autistic syndrome is defined by several abnormalities, mainly affecting social interaction skills. Disorders of the processes of processing facial and emotional stimuli, and particularly avoidance of gaze, have also been reported in this disorder. Some authors have suggested that these abnormalities may be explained, or at least contributed to, by the social disorder observed in this syndrome. The aim of this study was therefore to improve the understanding of the processes involved in perception AND the representation of faces expressing emotion in subjects with autism spectrum disorders (ASDs)., Methods: Eleven children with ASDs (mean developmental age 7 years 11 months) and eleven normally developing children (mean age 7 years 9 months) took part in three experiments. The first involved overall discrimination of emotions using photographs of faces expressing six basic emotions, the second required local emotional discrimination on the basis of isolated elements of the face (photographs of eyes and mouths isolated from the rest of the face), and for the third the children were asked to create faces expressing emotions by means of a jig-saw puzzle format, using photographs of isolated elements of the face (overall representation necessitating local discrimination)., Results: Our findings revealed that the normally developing children had difficulties with the process of local discrimination of emotions: their performance improved when overall perception was possible. In contrast, and astonishingly, the children with ASD were more able to discriminate isolated eyes expressing emotion than the controls, but their performance declined when overall processing was required., Discussion: Our results suggested that the emotional disorders observed in ASDs might be explained by greater skills in the processing of local information. This might explain the inability of children with ASDs to achieve coherent perception of their social environment and might also lead to the withdrawal that is characteristic of this disorder. These results also suggest that the gaze avoidance that is characteristic of individuals with ASDs is eliminated when eyes are presented alone. This gaze avoidance therefore seems to be related to the complexity and variability of this type of stimulus and not to the social nature of the stimulus., (Copyright © 2010 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Aim: Parity is associated with an increased risk of coronary heart disease and type 2 diabetes, possibly mediated by long-term modification of metabolic health. Studying associations between the number of children with health and disease in men in addition to women allows for differentiation between the social and lifestyle influences of child-rearing, and the biological influences of childbearing. We sought to determine whether the number of children is associated with the incidence of raised fasting glucose (fasting plasma glucose≥6.1 mmol/L) and changes in glucose, insulin, insulin resistance and β-cell function over 9-years., Methods: Analysis of 1798 women and 1737 men from the DESIR study., Results: The number of children was associated with change in fasting glucose for women (P(trend)=0.02) and men (P(trend)=0.03), and increased incidence of raised fasting glucose by 30% (95% CI: 15, 47%) per child for men, but not women (3% [95% CI: -8, 15%]). There was a J-shaped association between number of children and change in insulin (P=0.01) and insulin resistance (P=0.005) for women, and a reduction in β-cell function in parous women (P=0.07). Men with children had increases in insulin (P=0.02), insulin resistance (P=0.02), and β-cell function (P=0.07)., Conclusions: The number of children a person has is associated with changes in metabolic health indices long after childbirth for both men and women. The distinct gender differences in deterioration of metabolic health indices emphasize that childbearing and child-rearing are likely to have differential influences on metabolic health., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established., Literature Findings: To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of "Broad Autism Phenotype" related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However, strategies useful to characterize such phenotypic markers (for example, electrophysiological markers) have to take into account that autism is an early neurodevelopmental disorder occurring during childhood when brain development and maturation are in process., Conclusion: Recent genetic results have improved our knowledge in genetic basis in autism. Nevertheless, correspondences with phenotypic markers remain challenging according to phenotypic and genotypic heterogeneity., (Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Dyslexia is a complex neurodevelopemental disorder that affects 5 to 10% of school-age children. This condition consists in a specific learning disability with a neurological origin. These learning difficulties are unexpected in relation to other cognitive abilities and the provision of efficient classroom instruction. A range of neurobiological investigations suggests that disruption of the parieto-temporo-occipital systems underlies a failure of skilled reading to develop. The observation that dyslexia is both a familial and heritable problem was made early on and was confirmed by twin studies. They also suggested that both genetic and environmental factors are involved. Several loci have been implicated in dyslexia, notably on chromosomes 2, 3, 6, 15 and 18 and some candidate genes have been proposed, but no functional mutation has yet been identified., Literature Review: Dyslexia seldom appears isolated and dyslexic people are very likely to present other kinds of learning disabilities or psychiatric disorders. Specific language impairment, often with a mild outcome, is the most frequently associated with dyslexia. Indeed, late language development is often reported by dyslexic patients and also occurs more frequently among their siblings. Genetic linkage studies suggest some common genetic factor underlying this comorbidity. Dyscalculia is associated with dyslexia in 25% of cases, but most people with dyscalculia do not have any sign of dyslexia. The question of whether dyscalculia associated with dyslexia and dyscalculia itself rely on the same cognitive impairment is still controversial. Impaired motor development is also a common feature that affects nearly 50% of dyslexics and dyslexia is frequent among dyspraxic patients. This association raises the discussion on the role of motor impairment in dyslexia's physiopathology and the cerebellar theory of dyslexia. Beyond its link with other learning disorders, the study of dyslexia's comorbidity highlights psychopathological issues. ADHD is the most frequent psychiatric disorder associated with dyslexia. Underpinnings of this link between the two disorders seem to rely on common cognitive and genetic factors. Some authors have proposed a candidate gene ADRA2A to determine the condition including ADHD and dyslexia. In addition, dyslexics are exposed to a higher risk of anxiodepressive and behavioural disorders. Dyslexic children experience three times more behavioural disorders and one third of children with behavioural problems turn out to be affected by dyslexia. The literature study reveals inconsistent findings about depressed mood among dyslexics, but evidence of a persistent increase in the rate of anxiety disorders. The authors put forward the impact of environmental factors to explain these psychiatric comorbidities., Conclusion: This review emphasizes dyslexia's comorbidities because they represent an important issue, both from a scientific and clinical point of view. Indeed, for clinicians, children showing multiple learning disabilities have specific reeducation and educational needs and dyslexics have a higher risk of emotional and behavioural disorders. On the other hand, dyslexia's comorbidity study provides a powerful method for researchers to investigate the still unknown physiopathology of dyslexia., (2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

We used event-related potentials to investigate how aging affects local contextual processing. Local context was defined as the occurrence of a short predictive series of visual stimuli before delivery of a target event. Stimuli were presented to either the left or right visual field and consisted of 15% targets (downward facing triangle) and 85% of equal numbers of three types of standards (triangles facing left, upwards and right). Recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a three-standard predictive sequence signaling the occurrence of a subsequent target event. Subjects pressed a button in response to targets. Predictive local context affected target detection by reducing the duration of stimulus evaluation compared to detection of non-predictive random targets comparably for both young and older adults, as shown by a P3b latency shift. The peak of an earlier latency context positivity, which was seen only in the predicted compared to the random target condition, was prolonged in the older population compared to young adults. Finally, older subjects elicited a late sustained positivity in the predictive condition, not seen in the younger subjects. Taken together, these findings suggest that local contextual effects on target detection processes are altered with age., (Copyright 2009 Elsevier Srl. All rights reserved.)

CT dacryocystography, performed under sterile technique and following local anesthesia, is well tolerated by patients. It is the imaging technique of choice in patients with persistent tearing following clinical examination with non-invasive procedures when patency of the lacrimal drainage system remains uncertain, when a dacryolith or tumor is suspected or following unsuccessful dacryocystorhinostomy. Two techniques are available: instillation or direct cannulation, either initially or after non-visualization of the nasolacrimal system after contrast instillation. Non-specific idiopathic stenosis at the mid portion of the nasolacrimal duct is the most frequent etiology in patients over 50 years old; dacryoliths are present in 5 to 20% of cases of nasolacrimal duct stenosis. CT dacryocystography also allows evaluation of surrounding structures (medicolegal) to identify variants and anomalies when surgery is contemplated to avoid potential complications.

Aim: Insulin resistance needs to be identified as early as possible in its development to allow targeted prevention programmes. Therefore, we compared various fasting surrogate indices for insulin sensitivity using the euglycaemic insulin clamp in an attempt to develop the most appropriate method for assessing insulin resistance in a healthy population., Methods: Glucose, insulin, proinsulin, glucagon, glucose tolerance, fasting lipids, liver enzymes, blood pressure, anthropometric parameters and insulin sensitivity (Mffm/I) using the euglycaemic insulin clamp were obtained for 70 normoglycaemic non-obese individuals. Spearman's rank correlations were used to examine the association between Mffm/I and various fasting surrogate indices of insulin sensitivity. A regression model was used to determine the weighting for each variable and to derive a formula for estimating insulin resistance. The clinical value of the surrogate indices and the new formula for identifying insulin-resistant individuals was evaluated by the use of receiver operating characteristic (ROC) curves., Results: The variables that best predicted insulin sensitivity were the HDL-to-total cholesterol ratio, the fasting NEFA and fasting insulin. The use of the lipid-parameter-based formula Mffm/I=12x[2.5x(HDL-c/total cholesterol)-NEFA] - fasting insulin appeared to have high clinical value in predicting insulin resistance. The correlation coefficient between Mffm/I and the new fasting index was higher than those with the most commonly used fasting surrogate indices for insulin sensitivity., Conclusion: A lipid-parameter-based index using fasting samples provides a simple means of screening for insulin resistance in the healthy population.