Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice.

Overtraining syndrome is a condition resulting from excessive training load associated with inadequate recovery and poor sleep quality, leading to performance decrements and fatigue. Here we hypothesized that vitamin D (VitD) deficiency is a lead factor in the development of the overtraining syndrome. To test this hypothesis, two groups of 60-week-old C57BL/6 mice followed a 16-week excessive eccentric-based overtraining by excessive downhill running with or without dietary VitD depletion (EX and EX-D- groups). Two control groups were trained by uphill running at the same load with or without VitD depletion (CX and CX-D- groups). Handgrip strength decreased throughout the protocol for all groups but the decrease was sharper in EX-D- group (VitD × training, p = 0.0427). At the end of the protocol, the mass of Triceps brachii muscle, which is heavily stressed by eccentric contractions, was reduced in eccentric-trained groups (training effect, p = 0.0107). This atrophy was associated with a lower concentration of the anabolic myokine IL-15 (training effect, p = 0.0314) and a tendency to a higher expression of the atrogene cathepsin-L (training effect, p = 0.0628). VitD depletion led to a 50% decrease of the fractional protein synthesis rate in this muscle (VitD effect, p = 0.0004) as well as decreased FGF21 (VitD effect, p = 0.0351) and increased osteocrin (VitD effect, p = 0.038) concentrations that would lead to metabolic defects. Moreover, the proportion of anti-inflammatory Th2 lymphocytes was significantly decreased by the combination of eccentric training with VitD depletion (vitD × training, p = 0.0249) suggesting a systemic inflammation. Finally, exploratory behavior time of mice was decreased by VitD depletion (VitD effect, p = 0.0146) suggesting a cognitive dysfunction. Our results suggest that VitD deficiency exacerbates the effects of overtraining.

The role of neuropsychological assessment in adults with attention deficit/hyperactivity disorders.

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and/or impulsivity. While ADHD was initially recognized as a childhood syndrome, scientific evidence accumulated to indicate that a significant proportion of ADHD children continue to experience symptoms of ADHD in adulthood. Moreover, the question of ADHD diagnosis can arise in adult patients who were not diagnosed in childhood. Currently, the diagnosis of ADHD in adulthood is based on the revised criteria described for children. However, their application for adults may be difficult for many reasons including compensation and comorbid disorders. To date, no clinical, neuropsychological, biological or imaging marker is available for the diagnosis of ADHD. Considering that ADHD is based on a neuropsychological model, in this article we will examine the usefulness of neuropsychological testing in the diagnosis in adults. We will first present diagnostic criteria of ADHD and the limits of their application in adults. We will then detail the neuropsychological data available in adult ADHD and the French and international clinical recommendations for neuropsychological assessment. Finally, we will explore the predictive value of neuropsychological scores in the diagnosis of ADHD and discuss key methodological points and perspectives for clinical research.

Complication risk factors related to central venous catheter in pediatric.

BACKGROUND: A prospective epidemiological study was carried out in the pediatric intensive care unit (ICU), at the Mayotte Hospital Center (MHC). The purpose of the study was to identify and to evaluate complications risk factors related to central venous catheterization. Improving side effects prevention and patients care was the second goal. METHOD: Data collection took place over a period of 10 months. The central approaches followed in the study were femoral, jugular and subclavian. Since the database is composed of qualitative and quantitative variables, the Chi2 test has been used to measure the association between two variables. RESULTS: The study was carried out on 101 patients. Five infectious risk factors on the 10 variables evaluated have been significantly highlighted: the number of punctures, the number of repair of the dressing, the duration of the catheterization, the exposure time and the parenteral nutrition administration. CONCLUSIONS: Evaluation of practices through audits, an appropriate training for the staff, the update and the standardization of procedures, development of standardized assembly of the devices should lower the incidence of complications related to the venous approach.

Inflammatory biomarkers in infective endocarditis: machine learning to predict mortality.

Infective endocarditis (IE) is the cardiac disease with the highest rates of mortality. New biomarkers that are able to identify patients at risk for death are required to improve patient management and outcome. This study aims to investigate if cytokines, chemokines and growth factors measured at IE diagnosis can predict mortality. Patients with definite IE, according to the Duke's modified criteria, were included. Using high-performance Luminex assay, 27 different cytokines, chemokines and growth factors were analyzed. Machine learning techniques were used for the prediction of death and subsequently creating a decision tree, in which the cytokines, chemokines and growth factors were analyzed together with C-reactive protein (CRP). Sixty-nine patients were included, 41 (59%) male, median age 54 [interquartile range (IQR) = 41-65 years] and median time between onset of the symptoms and diagnosis was 12 days (IQR = 5-30 days). The in-hospital mortality was 26% (n = 18). Proinflammatory cytokines interkeukin (IL)-15 and C-C motif chemokine ligand (CCL4) were found to predict death, adding value to CRP levels. The decision tree predicted correctly the outcome of 91% of the patients at hospital admission. The high-risk group, defined as CRP ≥ 72 mg/dL, IL-15 ≥ 5·6 fg/ml and CCL4 ≥ 6·35 fg/ml had an 88% in-hospital mortality rate, whereas the patients classified as low-risk had a mortality rate of 8% (P = < 0·001). Cytokines IL-15 and CCL4 were predictors of mortality in IE, adding prognostic value beyond that provided by CRP levels. Assessment of cytokines has potential value for clinical risk stratification and monitoring in IE patients.

Formulation, process conditions, and biological evaluation of dairy mixed gels containing fava bean and milk proteins: Effect on protein retention in growing young rats.

Food formulation and process conditions can indirectly influence AA digestibility and bioavailability. Here we investigated the effects of formulation and process conditions used in the manufacture of novel blended dairy gels (called "mixed gels" here) containing fava bean (Vicia faba) globular proteins on both protein composition and metabolism when given to young rats. Three mixed dairy gels containing casein micelles and fava bean proteins were produced either by chemical acidification (A) with glucono-δ-lactone (GDL) or by lactic acid fermentation. Fermented gels containing casein and fava bean proteins were produced without (F) or with (FW) whey proteins. The AA composition of mixed gels was evaluated. The electrophoretic patterns of mixed protein gels analyzed by densitometry evidenced heat denaturation and aggregation via disulfide bonds of fava bean 11S legumin that could aggregate upon heating of the mixtures before gelation. Moreover, fermented gels showed no particular protein proteolysis compared with gel obtained by GDL-induced acidification. Kinetics of acidification were also evaluated. The pH decreased rapidly during gelation of GDL-induced acid gel compared with fermented gel. Freeze-dried F, A, and FW mixed gels were then fed to 30 young (1 mo old) male Wistar rats for 21 d (n = 10/diet). Fermented mixed gels significantly increased protein efficiency ratio (+58%) and lean mass (+26%), particularly muscle mass (+9%), and muscle protein content (+15%) compared with GDL-induced acid gel. Furthermore, F and FW formulas led to significantly higher apparent digestibility and true digestibility (+7%) than A formula. Blending fava bean, casein, and whey proteins in the fermented gel FW resulted in 10% higher leucine content and significantly higher protein retention in young rats (+7% and +28%) than the F and A mixed gels, respectively. Based on protein gain in young rats, the fermented fava bean, casein, and whey mixed proteins gel was the most promising candidate for further development of mixed protein gels with enhanced nutritional benefits.

[Post-traumatic stress disorder in reaction to psychotic experience: A systematic revue]. / Le Trouble Stress Post-Traumatique secondaire à l'expérience de la psychose : une revue de littérature.

BACKGROUND: The update of the Post-Traumatic Stress Disorder (PTSD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM5) emphasizes the definition of psychological traumatism as an objective and external event. Nevertheless, the scientific debate about the criteriology of PTSD, its clinical pertinence for application and the role of subjective dimension appears still open. Although the relation between psychotrauma and psychosis has been well examined, in the way of trauma as a risk factor for the development of schizophrenia, the potential traumatism represented by the psychotic experience seems to be less known. OBJECTIVE: This paper aims to provide a state of the art about the PTSD in reaction to psychosis, defined as PTSD post psychosis (PTSD-PP), particularly in epidemiological and psychopathological terms. METHODS: We performed a bibliographic research on Pubmed using the keywords "post-traumatic stress disorder", "psychological trauma", "schizophrenia review", "psychosis", "first episode psychosis"« ¼, "recovery schizophrenia", with a first screening on titles and abstracts. An acute psychotic episode referred to a decompensation of any pathology of the DSM5-schizophrenia spectrum or other psychotic disorders or to a mood disorder with psychotic features. The articles exclusively interested in the traumatic impact of hospitalizations and treatment conditions were excluded. RESULTS: The literature noted that PTSD-PP affected about a quarter to a third of the psychotic patients interrogated during the recovery of an acute psychotic episode. The analytic epidemiology showed that the main validated risk factors for PTSD were also relevant in the development of PTSD-PP, including past traumatic history, childhood trauma and feeling of helplessness during the traumatic event. Criticizing the methodological heterogeneity through studies, the observational approach brought out the lack of clinical pertinence of the DSM5A criteria defining the traumatic event for PTSD. This criteriology failed to consider the subjective dimension of the threat to psychological integrity generated by a psychotrauma. Historical case studies presented a complete post-traumatic symptomatology in reaction to psychosis, suggesting that the supposed psychotic residual symptoms after acute phase could referr to actual traumatic reactions. The PTSD-PP process observed in descriptive research and patients' interviews appeared congruent with the cognitive model of PTSD elaborated by Ehlers and Clark. Indeed, psychotic patients developed negative appraisals about themselves, others and the world because of the occurrence and the content of their psychotic symptoms. Shame, fear of recurrence, intolerance to uncertainty and perception of losing control of one's mind were demonstrated as significantly related to PTSD-PP. A perception of current threat then settled, leading to adaptation strategies, possibly psychotic themselves, to avoid intrusions and others indices about their past psychotic episode. Thus, reliving syndrome, avoidance, emotional numbing could simulate a new psychotic exacerbation to an outer-observer. CONCLUSION: A psychotic experience could be traumatic for patients and lead to complete PTSD. Although it appears as a non-consensual clinical entity, from a likely epistemological slip of the definition of "psychotrauma", the consideration of potential PTSD-PP presents an undoubted clinical relevance. Indeed, it could help practioners to precise the semiological analysis of patients recovering from an acute psychotic episode; to impact the prognosis of psychosis, thinking about impairment on the quality of life and the affective and suicidal comorbidities; and to modify the therapeutic approach in the recovery of schizophrenia. In addition, the literature about psychotic recovery seems particularly related to the concept of "post-traumatic growth" (PTG). The inscription of a psychotic episode in a traumatic frame requires a clinical approach as close as possible to the subjectivity of the patient experience, beyond the evaluation of psychotic symptoms and its remission. The question of trauma-focused therapies applied to PTSD-PP opens the field for future research.

Effect of a specific exercise strategy on strength and proprioception in volleyball players with infraspinatus muscle atrophy.

Infraspinatus muscle atrophy is common in professional volleyball players, but it is unclear whether commonly observed strength and proprioception deficits can be reversed with training. Fifty-four participants were recruited into an infraspinatus atrophy group (IAG, n = 18) and a non-atrophy group (NAG, n = 18) of elite volleyballers plus a healthy non-athletic control group (CG, n = 18). IAG were trained with a progressive, specific shoulder external rotator strengthening routine for 32 sessions over 8 weeks. Shoulder external rotation peak torque (SERPT) and threshold to detect passive movement (TTDPM) and joint position sense (JPS) were measured before and after the intervention. At baseline, no significant difference was detected in strength or proprioception between the injured and control groups, but the normal athletes were stronger and had better proprioception than either IAG or CG (P < .001). IAG (d = 2.78) and NAG (d = 0.442) improved strength significantly after training. IAG improved TTDM and JPS (P < .001, d = -0.719 and -2.942, respectively) but were still worse than NAG (P < .001). Elite volleyball players with Infraspinatus muscle atrophy have strength and proprioception deficits which can be improved by a specific exercise program to normal but not elite athlete control levels.

Impairment of adipose tissue in Prader-Willi syndrome rescued by growth hormone treatment.

BACKGROUND: Prader-Willi syndrome (PWS) results from abnormalities in the genomic imprinting process leading to hypothalamic dysfunction with an alteration of growth hormone (GH) secretion. PWS is associated with early morbid obesity and short stature which can be efficiently improved with GH treatment. OBJECTIVES: Our aims were to highlight adipose tissue structural and functional impairments in children with PWS and to study the modifications of those parameters on GH treatment. SUBJECTS AND METHODS: Plasma samples and adipose tissue biopsies were obtained from 23 research centers in France coordinated by the reference center for PWS in Toulouse, France. Lean controls (n=33), non-syndromic obese (n=53), untreated (n=26) and GH-treated PWS (n=43) children were enrolled in the study. Adipose tissue biopsies were obtained during scheduled surgeries from 15 lean control, 7 untreated and 8 GH-treated PWS children. RESULTS: Children with PWS displayed higher insulin sensitivity as shown by reduced glycemia, insulinemia and HOMA-IR compared with non-syndromic obese children. In contrast, plasma inflammatory cytokines such as TNF-α, MCP-1 and IL-8 were increased in PWS. Analysis of biopsies compared with control children revealed decreased progenitor cell content in the stromal vascular fraction of adipose tissue and an impairment of lipolytic response to ß-adrenergic agonist in PWS adipocytes. Interestingly, both of these alterations in PWS seem to be ameliorated on GH treatment. CONCLUSION: Herein, we report adipose tissue dysfunctions in children with PWS which may be partially restored by GH treatment.

Role of proximal gut exclusion from food on glucose homeostasis in patients with Type 2 diabetes.

AIMS: To report Type 2 diabetes-related outcomes after the implantation of a duodenal-jejunal bypass liner device and to investigate the role of proximal gut exclusion from food in glucose homeostasis using the model of this device. METHODS: Sixteen patients with Type 2 diabetes and BMI <36 kg/m(2) were evaluated before and 1, 12 and 52 weeks after duodenal-jejunal bypass liner implantation and 26 weeks after explantation. Mixed-meal tolerance tests were conducted over a period of 120 min and glucose, insulin and C-peptide levels were measured. The Matsuda index and the homeostatic model of assessment of insulin resistance were used for the estimation of insulin sensitivity and insulin resistance. The insulin secretion rate was calculated using deconvolution of C-peptide levels. RESULTS: Body weight decreased by 1.3 kg after 1 week and by 2.4 kg after 52 weeks (P < 0.001). One year after duodenal-jejunal bypass liner implantation, the mean (sem) HbA(1c) level decreased from 71.3 (2.4) mmol/mol (8.6[0.2]%) to 58.1 (4.4) mmol/mol (7.5 [0.4]%) and mean (sem) fasting glucose levels decreased from 203.3 (13.5) mg/dl to 155.1 (13.1) mg/dl (both P < 0.001). Insulin sensitivity improved by >50% as early as 1 week after implantation as measured by the Matsuda index and the homeostatic model of assessment of insulin resistance (P < 0.001), but there was a trend towards deterioration in all the above-mentioned variables 26 weeks after explantation. Fasting insulin levels, insulin area under the curve, fasting C-peptide, C-peptide area under the curve, fasting insulin and total insulin secretion rates did not change during the duodenal-jejunal bypass liner implantation period or after explantation. CONCLUSIONS: The duodenal-jejunal bypass liner improves glycaemia in overweight and obese patients with Type 2 diabetes by rapidly improving insulin sensitivity. A reduction in hepatic glucose output is the most likely explanation for this improvement.

Exploring the genetic causes of isolated short stature. What has happened to idiopathic short stature?

Statural growth is underpinned by development of the growth plate during the process of endochondral ossification, which is strongly regulated by numerous local factors (intracellular, paracrine and extracellular matrix factors) and systemic factors (nutrition, hormones, proinflammatory cytokines and extracellular fluids). This explains why growth retardation can be associated with numerous pathologies, particularly genetic syndromes, hormonal or inflammatory conditions, or gastrointestinal disorders having a nutritional impact. However, in most cases (80%), no specific aetiology is found after clinical investigation and conventional additional tests have been carried out. In such cases, "idiopathic" short stature is diagnosed, which includes patients presenting with constitutional delay of growth and development and familial short stature, but also patients with very subtle constitutional skeletal dysplasia which are not easily identifiable. In recent years, new methods of genetic investigation (e.g. gene panels, exome or genome sequencing) have made it possible to identify many genetic variants associated with apparently isolated short stature. Indeed, it is still difficult to estimate the proportion of patients presenting with idiopathic short stature for which a molecular diagnosis of monogenic conditions could be made. This estimate varies hugely depending on the thoroughness of the clinical, laboratory and radiological assessments performed prior to molecular analysis, since retrospective analysis of positive cases usually reveals subtle signs of underlying syndromes or rare skeletal disorders. Molecular diagnosis in children is important to be able to offer genetic counselling and to organise patient management. Moreover, improved understanding of the molecular basis of these cases of short stature opens up numerous possibilities for more specific treatments targeting the growth plate. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

A linear-polymer-based lactoferrin-selective recognition element for an ELISA mimic: A proof of concept.

The synthesis of polymers with tailored properties for the recognition of macromolecules such as proteins is challenging. In this work, the synthesis of a new polymer format, a linear polymer (LP), as the selective recognition element for the globular protein lactoferrin (LF) is proposed as a proof-of-concept study. For the synthesis, a solid-phase strategy using the reversible deactivation radical polymerisation (RDRP) mechanism is proposed. This approach, which is usually used in molecular imprinting, involves the immobilisation of LF on the surface of a solid support, but, unlike classical imprinting, a cross-linker in the polymerisation mixture is not required. Consequently, the copolymer is soluble and flexible, thus overcoming the drawbacks associated with traditional synthetic polymers for macromolecule imprinting. This new polymer format has great potential for replacing natural antibodies in bioassays such as enzyme-linked immunosorbent assays (ELISA), dot blot, western blot, or pull-down. In our case, the linear polymer was used as a recognition element to replace natural antibodies in a LF-selective ELISA. The responses of the linear polymer between LF concentrations of 0.1 nM and 0.25 µM were studied, and a significant difference was observed between the non-specific signals and the signals measured in the presence of the polymeric material. Further, the response versus log concentration curves were fitted to a logistic equation, allowing estimation of the EC50 value: 11.8 ± 1.4 nM. We also confirmed the selective detection of LF using the competitive inhibition of the selective LF-biotin conjugate (LF-Bi) binding to the plastic receptor (LP) for closely related proteins (e.g. those having similar molecular weights or isoelectric points) such as human lysozyme, trypsin, and albumin, which are present in human body fluids. The system presents a cross-reactivity value or selectivity of 1.95% for lysozyme, 0.028% for trypsin, and 0.016% for albumin. The applicability of this method for the determination of urine LF levels in inflammatory and infectious diseases of the human urinary tract is also demonstrated.

Vitamin D and calcium intakes in general pediatric populations: A French expert consensus paper.

OBJECTIVES: Nutritional vitamin D supplements are often used in general pediatrics. Here, the aim is to address vitamin D supplementation and calcium nutritional intakes in newborns, infants, children, and adolescents to prevent vitamin D deficiency and rickets in general populations. STUDY DESIGN: We formulated clinical questions relating to the following categories: the Patient (or Population) to whom the recommendation will apply; the Intervention being considered; the Comparison (which may be "no action," placebo, or an alternative intervention); and the Outcomes affected by the intervention (PICO). These PICO elements were arranged into the questions to be addressed in the literature searches. Each PICO question then formed the basis for a statement. The population covered consisted of children aged between 0 and 18 years and premature babies hospitalized in neonatology. Two groups were assembled: a core working group and a voting panel from different scientific pediatric committees from the French Society of Pediatrics and national scientific societies. RESULTS: We present here 35 clinical practice points (CPPs) for the use of native vitamin D therapy (ergocalciferol, vitamin D2 and cholecalciferol, vitamin D3) and calcium nutritional intakes in general pediatric populations. CONCLUSION: This consensus document was developed to provide guidance to health care professionals on the use of nutritional vitamin D and dietary modalities to achieve the recommended calcium intakes in general pediatric populations. These CPPs will be revised periodically. Research recommendations to study key vitamin D outcome measures in children are also suggested.

Allergic contact dermatitis due to a PVC table cover.

BACKGROUND: Plastics are a common cause of occupational skin disorders such as irritant or allergic contact dermatitis (ACD). CASE REPORT: We report a case of occupational ACD due to a polyvinyl chloride (PVC) plastic table cover used as a mouse pad for which we performed patch tests and obtained positive patch tests for the PVC table cover. Composition testing revealed the presence of phthalates and phosphites, which may represent the specific allergens. CONCLUSIONS: Contact with some of the chemical components of the PVC table cover, together with a combination of sweating and friction, may have enhanced the allergenicity of these components. Workplace adjustment resulted in disappearance of the dermatitis.

Patellar tendinopathy outcome predictors in jumping athletes: feasibility of measures for a cohort study.

OBJECTIVES: The main aim was to assess feasibility by testing data collection procedures for a cohort study. Measurements validity and reliability were secondary objectives. DESIGN: Feasibility study. SETTING: Combination of remote contact, assessment in clinic and biomechanical evaluation. PARTICIPANTS: 36 jumping athletes (female:17, male:19) equally spread between those with patellar tendinopathy, other knee problems and controls. MAIN OUTCOME MEASURES: Measurements validity, reliability and feasibility. RESULTS: There was no systematic difference between administration methods for patient reported outcome measures and miscellaneous questions (range of d = -0.32 to 0.26) without any order effect (all p > 0.05) except KOOS-PF (p = 0.02). Questionnaires' inter-session reliability was moderate to excellent (ICCs = 0.68-0.93). Pain maps were 94% matched between methods. Training load recall percentage decreased until week-3 with only 20% maintaining a training diary completing the full 6 weeks. The graded loaded challenge was clinically applicable, biomechanically valid with increasing load through progression and reliable (ICCs = 0.63-0.98). CONCLUSION: The tested questionnaires were valid and reliable for online use, therefore being suitable for clinical and research purposes. A shorter survey to reduce burden and collecting training load using shorter recall duration should improve feasibility. Biomechanical measures were valid and reliable, and a graded loaded challenge, suitable for further testing, has been defined.

Guidelines for the management of children at risk of secondary bone fragility: Expert opinion of a French working group.

The current French national guidelines were elaborated by a working group consisting of experts in the field of pediatric endocrinology, rheumatology, hepatogastroenterology, nephrology, and pneumology. A systematic search was undertaken of the literature published between 2008 and 2018 and indexed in PubMed. The recommendations developed were then validated by an external evaluation group comprising representatives from the various highly specialized fields in pediatrics, representatives of the societies and groups supporting the development of the guidelines, and representatives of different healthcare professions. The objective of these guidelines was to detail the current optimal management of children at risk of secondary bone fragility.

Verbal Fluency Development Across Childhood: Normative Data from Brazilian-Portuguese Speakers and Underlying Cognitive Processes.

OBJECTIVE: Verbal fluency (VF) tasks are widely used to investigate children's lexical knowledge and executive functions skills. Consistency of measurement of the strategic retrieval components is still an issue and performance of Brazilian-Portuguese speaking children are currently not available. A cross-sectional study investigated the effects of age, school type (public × private) and the influence of language, memory and inhibitory control on VF. METHOD: We assessed 414 Brazilian children, aged 6-12, in the number of words produced and both clustering and switching components, with two measures of VF: letter (LVF) and semantic (SVF). RESULTS: Analysis of the number of words produced showed a significant increase between 6-8-year-olds, 9-10-year-olds and 11-12-year-olds in SVF, while in LVF, the differences were significant only in the later age group. In SVF, the numbers of clusters and switches increased with age, whereas in LVF, the number of switches increased in all age groups, but clusters increased only in the older group. Structural equation model analyses showed that oral and written language, verbal memory and inhibitory control are associated with VF performance and IQ, while age mediated VF performance. CONCLUSIONS: The results indicate a different development pattern between LVF and SVF in the number of words produced and in clustering and switching, with the latter predicting VF performance in words produced. VF development is shown to depend on language, memory and inhibitory control. Our results have important implications to clinical neuropsychology.

Neurophysiological changes after cognitive-motor tasks in Parkinson's disease patients with deep brain stimulation.

Chronic deep brain stimulation (CDBS) is a surgical treatment that reduces the cardinal signs of Parkinson's disease (PD). Although CDBS has been in use for a long time, very little has been reported on its supposed effects on cognition, particularly in relation to implants in the subthalamic nucleus. The results of the rare studies that do exist are controversial, and in many cases the studies have several design flaws. The present study compared cortical activation during three tasks (action execution, action observation and motor imagery) in PD patients with and without subthalamic implants. The study sample consisted of 36 volunteers, divided into three groups: healthy controls, PD patients with CDBS of the subthalamic nucleus, and PD patients without CDBS. Through a quantitative electroencephalogram assessment, absolute beta power was examined to observe the interaction between group and cognitive motor tasks. The electrodes at sites Fp1, Fp2, F7, F8, F3, Fz and F4, located in the prefrontal and frontal regions, were analyzed and a Group x Task interaction (p < 0.05) was observed for all of them. These findings suggest that CDBS of the subthalamic nucleus is efficient in reducing some of the effects of PD in these study tasks. At the same time, the dysfunctions found in several cortical areas, characteristic of PD, limited the effects of the CDBS. The results of this study suggest that CDBS of the subthalamic nucleus can modulate cognitive-motor aspects of PD.

Immunohistochemical localization of CB1 cannabinoid receptors in frontal cortex and related limbic areas in obese Zucker rats: effects of chronic fluoxetine treatment.

In the present study, we report on the application of two specific polyclonal antibodies to different intracellular domains of the CB1 cannabinoid receptor to define the expression of the neural CB1 cannabinoid receptor at the histochemical level in frontal cortex and related limbic areas of the obese Zucker rats. Higher levels of CB1 receptor expression in frontal, cingulated and piriform cortex, without differences in temporal, parietal and occipital cortex, were observed in obese Zucker rats, with respect to their lean littermates. CB1 phosphorylated receptor (CB1-P) levels were also higher in frontal, temporal, parietal and occipital cortex in obese rats with respect to lean controls. Potential involvement of brain cortical CB1 cannabinoid receptors in the long-term effects of fluoxetine was studied. Experimental animals were administered with fluoxetine (10 mg/kg, i.p.) daily for 3 weeks, whereas the control group was given 0.9% NaCl solution. In obese Zucker rats, a significant decrease in CB1 receptor levels, measured by western blot, was observed in brain cortex after fluoxetine treatment. Immunostaining for CB1 receptor expression was also carried out, showing a significant decrease in the density of neural cells positive for CB1 receptor in frontal, cingulate and piriform cortex, without changes in parietal, temporal and occipital regions. Regional prosencephalic immunostaining for CB1-P receptor level showed a significant decrease in the density of stained neural cells in frontal, temporal and parietal cortex, without changes in cingulated, piriform and occipital cortex. These results suggest the involvement of endocannabinoid system in the chronic effects of fluoxetine, especially in the frontal cortex.

[New molecular mechanisms of growth hormone insensitivity]. / Nouveaux mécanismes moléculaires impliqués dans l'insensibilité à l'hormone de croissance.

Growth hormone (GH), secreted by the anterior pituitary into the circulation, binds to membrane receptors in target tissues to stimulate body growth; most of its effects is mediated by the insulin-like growth factor 1 (IGF-1). In addition to promoting growth, GH has important metabolic actions. The syndrome of GH insensitivity (GHI) was first identified in 1966 by Laron et al. in three children with clinical phenotype characteristic of growth hormone deficiency but associated with elevated serum concentration of GH. Direct evidence of a GH receptor (GHR) abnormality was provided in 1989. More recently, molecular abnormalities in the postreceptor signalling mechanism were found. Mutations of signal transducer and activator of transcription 5b (Stat5b) were reported in patients with growth retardation and primary immunodeficiency. Mutations of the tyrosin phosphatase Shp2 were identified in patients affected by Noonan syndrome characterized by short stature, cardiopathy and increased risk of leukaemia. The unmasking of the molecular bases for these defects will contribute greatly to our future understanding of both normal and aberrant growth. Moreover, this knowledge should bring insight on cancerogenesis or immunodeficiency caused by cytokines resistance.