Volumetric MRI changes, cognition and personality traits in old age depression.

BACKGROUND: The presence of cognitive and structural deficits in euthymic elderly depressed patients remains a matter of debate. Integrative aetiological models assessing concomitantly these parameters as well as markers of psychological vulnerability such as persistent personality traits, are still lacking for this age group. METHODS: Cross-sectional comparisons of 38 elderly remitted patients with early-onset depression (EOD) and 62 healthy controls included detailed neuropsychological assessment, estimates of brain volumes in limbic areas and white matter hyperintensities, as well as evaluation of the Five-Factor personality dimensions. RESULTS: Both cognitive performances and brain volumes were preserved in euthymic EOD patients. No significant group differences were observed in white matter hyperintensity scores between the two groups. In contrast, EOD was associated with significant increase of Neuroticism and decrease of Extraversion facet scores. LIMITATIONS: Results concern the restricted portion of EOD patients without psychiatric and physical comorbidities. Future longitudinal studies are necessary to determine the temporal relationship between the occurrence of depression and personality dimensions. CONCLUSIONS: After remission from acute depressive symptoms, cognitive performances remain intact in elderly patients with EOD. In contrast to previous observations, these patients display neither significant brain volume loss in limbic areas nor increased vascular burden compared to healthy controls. Further clinical investigations on EOD patterns of vulnerability in old age will gain from focusing on psychological features such as personality traits rather than neurocognitive clues.

The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis.

OBJECTIVES: To develop data-driven criteria for clinically inactive disease on and off therapy for juvenile dermatomyositis (JDM). METHODS: The Paediatric Rheumatology International Trials Organisation (PRINTO) database contains 275 patients with active JDM evaluated prospectively up to 24 months. Thirty-eight patients off therapy at 24 months were defined as clinically inactive and included in the reference group. These were compared with a random sample of 76 patients who had active disease at study baseline. Individual measures of muscle strength/endurance, muscle enzymes, physician's and parent's global disease activity/damage evaluations, inactive disease criteria derived from the literature and other ad hoc criteria were evaluated for sensitivity, specificity and Cohen's κ agreement. RESULTS: The individual measures that best characterised inactive disease (sensitivity and specificity >0.8 and Cohen's κ >0.8) were manual muscle testing (MMT) ≥78, physician global assessment of muscle activity=0, physician global assessment of overall disease activity (PhyGloVAS) ≤0.2, Childhood Myositis Assessment Scale (CMAS) ≥48, Disease Activity Score ≤3 and Myositis Disease Activity Assessment Visual Analogue Scale ≤0.2. The best combination of variables to classify a patient as being in a state of inactive disease on or off therapy is at least three of four of the following criteria: creatine kinase ≤150, CMAS ≥48, MMT ≥78 and PhyGloVAS ≤0.2. After 24 months, 30/31 patients (96.8%) were inactive off therapy and 69/145 (47.6%) were inactive on therapy. CONCLUSION: PRINTO established data-driven criteria with clearly evidence-based cut-off values to identify JDM patients with clinically inactive disease. These criteria can be used in clinical trials, in research and in clinical practice.

GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues.

Based on homology with GLUT1-5, we have isolated a cDNA for a novel glucose transporter, GLUTX1. This cDNA encodes a protein of 478 amino acids that shows between 29 and 32% identity with rat GLUT1-5 and 32-36% identity with plant and bacterial hexose transporters. Unlike GLUT1-5, GLUTX1 has a short extracellular loop between transmembrane domain (TM) 1 and TM2 and a long extracellular loop between TM9 and TM10 that contains the only N-glycosylation site. When expressed in Xenopus oocytes, GLUTX1 showed strong transport activity only after suppression of a dileucine internalization motif present in the amino-terminal region. Transport activity was inhibited by cytochalasin B and partly competed by D-fructose and D-galactose. The Michaelis-Menten constant for glucose was approximately 2 mM. When translated in reticulocytes lysates, GLUTX1 migrates as a 35-kDa protein that becomes glycosylated in the presence of microsomal membranes. Western blot analysis of GLUTX1 transiently expressed in HEK293T cells revealed a diffuse band with a molecular mass of 37-50 kDa that could be converted to a approximately 35-kDa polypeptide following enzymatic deglycosylation. Immunofluorescence microscopy detection of GLUTX1 transfected into HEK293T cells showed an intracellular staining. Mutation of the dileucine internalization motif induced expression of GLUTX1 at the cell surface. GLUTX1 mRNA was detected in testis, hypothalamus, cerebellum, brainstem, hippocampus, and adrenal gland. We hypothesize that, in a similar fashion to GLUT4, in vivo cell surface expression of GLUTX1 may be inducible by a hormonal or other stimulus.

A novel device for reducing hemolysis provoked by cardiotomy suction during open heart cardiopulmonary bypass surgery: a randomized prospective study.

Since the inception of cardiopulmonary bypass (CPB), little progress has been made concerning the design of cardiotomy suction (CS). Because this is a major source of hemolysis, we decided to test a novel device (Smartsuction [SS]) specifically aimed at minimizing hemolysis during CPB in a clinical setting. Block randomization was carried out on a treated group (SS, n=28) and a control group (CTRL, n=26). Biochemical parameters were taken pre-, peri-, and post CPB and were compared between the two groups using the Student's t-test with statistical significance when P<0.05. No significant differences in patient demographics were observed between the two groups. Lactate dehydrogenase (LDH) and plasma free hemoglobin (PFH) pre-CPB were comparable for the CTRL and SS groups, respectively. LDH peri-CPB was 275+/-100 U/L versus 207+/-83 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 486+/-204 mg/L versus 351+/-176 mg/L for the CTRL and SS groups, respectively (P<0.05). LDH post CPB was 354+/-116 U/L versus 275+/-89 U/L for the CTRL and SS groups, respectively (P<0.05). PFH was 549+/-271 mg/L versus 460+/-254 mg/L for the CTRL and SS groups, respectively (P<0.05). Preoperative hematocrit (Hct) of 43+/-5% (CTRL) versus 37+/-5% (SS), and hemoglobin (Hb) of 141+/-16 g/L (CTRL) versus 122+/-17 g/L (SS) were significantly lower in the SS group. However, when normalized (N), the SS was capable of conserving Hct, Hb, and erythrocyte count perioperatively. Erythrocytes (N) were 59+/-5% (CTRL) versus 67+/-9% (SS); Hct (N) was 59+/-6% (CTRL) versus 68+/-9% (SS), and Hb (N) was 61+/-6% (CTRL) versus 70+/-10% (SS) (all P<0.05). This novel SS device evokes significantly lowered blood PFH and LDH values peri- and post CPB compared with the CTRL blood using a CS system. The SS may be a valuable alternative compared to traditional CS techniques.

Treatment of central retinal vein occlusion-related macular edema with intravitreal bevacizumab (Avastin): preliminary results.

PURPOSE: To assess the safety and efficacy of treatment of macular edema secondary to central retinal vein occlusion (CRVO) with intravitreal bevacizumab. PATIENTS AND METHOD: The ongoing prospective study included 8 consecutive patients (8 eyes) with macular edema secondary to CRVO (6 non ischemic and 2 ischemic), treated with intravitreal injection of 1.25 mg (0.05 mL) of bevacizumab. Main outcome was best corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by optical coherence tomography monthly during one year. Retreatment criteria include decrease of BCVA, persistence of macular edema on angiograms and increase of CFT. RESULTS: Mean age of the eight patients was 68 years (range: 50-82 years). Mean duration of symptoms before injection was 98 days (range: 3-289). Mean follow-up was 3.25 months. At baseline, mean BCVA was 0.84 logMar and mean baseline CFT was 771 microm. Mean BCVA was 0.36 and mean CFT thickness was 275 microm (n = 8) at month 1, 0.41 and 411 microm at month 2 (n = 7), 0.3 and 344 microm at month 3 (n = 6), 0.3 and 397 microm at month 4 (n = 5), respectively. In 75 % of patients, a single injection was not sufficient, and retreatment needed. No serious adverse events were observed. CONCLUSIONS: Treatment of macular edema secondary to CRVO with intravitreal bevacizumab injection of 1.25 mg was well tolerated and associated with marked macular thickness reduction and BCVA improvement in all patients. A trend towards reduction of foveal thickness and improvement of visual acuity was observed in both acute and chronic CRVO.

Primary pineal tumors: outcome and prognostic factors-a study from the Rare Cancer Network (RCN).

PURPOSE: To better define outcome and prognostic factors in primary pineal tumors. MATERIALS AND METHODS: Thirty-five consecutive patients from seven academic centers of the Rare Cancer Network diagnosed between 1988 and 2006 were included. Median age was 36 years. Surgical resection consisted of biopsy in 12 cases and resection in 21 (2 cases with unknown resection). All patients underwent radiotherapy and 12 patients received also chemotherapy. RESULTS: Histological subtypes were pineoblastoma (PNB) in 21 patients, pineocytoma (PC) in 8 patients and pineocytoma with intermediate differentiation in 6 patients. Six patients with PNB had evidence of spinal seeding. Fifteen patients relapsed (14 PNB and 1 PC) with PNB cases at higher risk (p = 0.031). Median survival time was not reached. Median disease-free survival was 82 months (CI 50 % 28-275). In univariate analysis, age younger than 36 years was an unfavorable prognostic factor (p = 0.003). Patients with metastases at diagnosis had poorer survival (p = 0.048). Late side effects related to radiotherapy were dementia, leukoencephalopathy or memory loss in seven cases, occipital ischemia in one, and grade 3 seizures in two cases. Side effects related to chemotherapy were grade 3-4 leucopenia in five cases, grade 4 thrombocytopenia in three cases, grade 2 anemia in two cases, grade 4 pancytopenia in one case, grade 4 vomiting in one case and renal failure in one case. CONCLUSIONS: Age and dissemination at diagnosis influenced survival in our series. The prevalence of chronic toxicity suggests that new adjuvant strategies are advisable.

Pédiatrie. 4. La calprotectine fécale en pédiatrie: utilisation et interprétation [Pediatrics. Fecal calprotectin in children: use and interpretation].

Fecal calprotectin is a small protein released mainly by neutrophils. It is recognized as a reliable, easy and non-invasive biomarker of gastro-intestinal inflammation. Normal values vary with age, with higher cut-off values during the first year of life (<350 microg/g) than in children (<275 microg/g) or adults (<50 microg/g). Fecal calprotectin can be a useful tool in initial evaluation of recurrent abdominal pain, helping to distinguish between functional gastro-intestinal disorders, where it is normal, and inflammatory bowel disease (IBD). It is not a specific marker of IBD but is increased in other situations of gastro-intestinal inflammation. In patients with IBD, fecal calprotectin is used to monitor treatment response.

Social personality trait and fitness.

Several recent studies have explored various aspects of animal personality and their ecological consequences. However, the processes responsible for the maintenance of personality variability within a population are still largely unknown. We have recently demonstrated that social personality traits exist in the common lizard (Lacerta vivipara) and that the variation in sociability provides an explanation for variable dispersal responses within a given species. However, we need to know the fitness consequences of variation in sociability across environmental contexts in order to better understand the maintenance of such variation. In order to achieve this, we investigated the relationship between sociability and survival, body growth and fecundity, in one-year-old individuals in semi-natural populations with varying density. 'Asocial' and 'social' lizards displayed different fitness outcomes in populations of different densities. Asocial lizards survived better in low-density populations, while social females reproduced better. Spatiotemporal variation in environmental conditions might thus be the process underlying the maintenance of these personality traits within a population. Finally, we also discuss the position of sociability in a more general individual behavioural pattern including boldness, exploration and aggressiveness.

Amino acid identity and/or position determines the proteasomal cleavage of the HLA-A*0201-restricted peptide tumor antigen MAGE-3271-279.

The proteasome plays a crucial role in the proteolytic processing of antigens presented to T cells in the context of major histocompatibility complex class I molecules. However, the rules governing the specificity of cleavage sites are still largely unknown. We have previously shown that a cytolytic T lymphocyte-defined antigenic peptide derived from the MAGE-3 tumor-associated antigen (MAGE-3(271-279), FLWGPRALV in one-letter code) is not presented at the surface of melanoma cell lines expressing the MAGE-3 protein. By using purified proteasome and MAGE-3(271-279) peptides extended at the C terminus by 6 amino acids, we identified predominant cleavages after residues 278 and 280 but no detectable cleavage after residue Val(279), the C terminus of the antigenic peptide. In the present study, we have investigated the influence of Pro(275), Leu(278), and Glu(280) on the proteasomal digestion of MAGE-3(271-285) substituted at these positions. We show that positions 278 and 280 are major proteasomal cleavage sites because they tolerate most amino acid substitutions. In contrast, the peptide bond after Val(279) is a minor cleavage site, influenced by both distal and proximal amino acid residues.

Dominant negative MyD88 proteins inhibit interleukin-1beta /interferon-gamma -mediated induction of nuclear factor kappa B-dependent nitrite production and apoptosis in beta cells.

Insulin-dependent diabetes mellitus is an autoimmune disease in which pancreatic islet beta cells are destroyed by a combination of immunological and inflammatory mechanisms. In particular, cytokine-induced production of nitric oxide has been shown to correlate with beta cell apoptosis and/or inhibition of insulin secretion. In the present study, we investigated whether the interleukin (IL)-1beta intracellular signal transduction pathway could be blocked by overexpression of dominant negative forms of the IL-1 receptor interacting protein MyD88. We show that overexpression of the Toll domain or the lpr mutant of MyD88 in betaTc-Tet cells decreased nuclear factor kappaB (NF-kappaB) activation upon IL-1beta and IL-1beta/interferon (IFN)-gamma stimulation. Inducible nitric oxide synthase mRNA accumulation and nitrite production, which required the simultaneous presence of IL-1beta and IFN-gamma, were also suppressed by approximately 70%, and these cells were more resistant to cytokine-induced apoptosis as compared with parental cells. The decrease in glucose-stimulated insulin secretion induced by IL-1beta and IFN-gamma was however not prevented. This was because these dysfunctions were induced by IFN-gamma alone, which decreased cellular insulin content and stimulated insulin exocytosis. These results demonstrate that IL-1beta is involved in inducible nitric oxide synthase gene expression and induction of apoptosis in mouse beta cells but does not contribute to impaired glucose-stimulated insulin secretion. Furthermore, our data show that IL-1beta cellular actions can be blocked by expression of MyD88 dominant negative proteins and, finally, that cytokine-induced beta cell secretory dysfunctions are due to the action of IFN-gamma.