[Management of cardiovascular co-morbidities in young patients with early onset psychosis: State of the art and therapeutic perspectives]. / Prise en charge des comorbidités cardio-vasculaires chez les jeunes patients souffrant d'une psychose débutante : état des lieux et perspectives thérapeutiques.

Patients with psychiatric disorders have a decrease in their life expectancy. Excess mortality of patients with schizophrenia was demonstrated by a meta-analysis in the late 1990s and has not decreased for the past 30years. A recent meta-analysis including nearly 250,000 patients with schizophrenia found an average decrease in life expectancy of 14.5years (CI95: 11,2-17,8), more important for men than for women: 15.9 (CI95: 13,8-18,0) vs 13.6 (CI95: 11,4-15,8). A closer look at the somatic comorbidities, including metabolic syndrome, and investigation of causes of death of these patients highlighted already well-known factors, namely late diagnosis and insufficient treatment of physical diseases, side effects of antipsychotics, unhealthy lifestyle (poor diet, smoking, excessive alcohol consumption and lack of exercise), and higher risk of suicide and accident. Concerning ultra-high risk (UHR) patients, a 2016 meta-analysis of 47 studies evaluated the cardiovascular risk factors. They reported a higher prevalence of smoking in UHR (odds ratio 2,3) and a lower level of physical activity associated with a normal BMI (Body Mass Index) compared to the control population. A meta-analysis about patients with a first episode of psychosis (FEP) found reduced total and LDL cholesterol levels and an increased triglyceride level compared to the control population. One study found alteration of the fasting plasmatic levels of glucose and insulin, as well as insulin resistance in FEP patients, compared to controls albeit the HbA1c level was not significantly different. A meta-analysis reported a prevalence of metabolic syndrome of 10 % in FEP or drug naïve patients versus 35 % and 20 % in treated and untreated patients with chronic schizophrenia respectively. Somatic comorbidities usually appear during the first two years of the disease. Some interventions have proven their efficacy in reducing the occurrence of metabolic syndrome and other cardiovascular risk factors. For instance, metformin, a treatment for type 2 diabetes that is allowed from the age of 10, has shown benefits in children and adolescents receiving second-generation antipsychotics in a recent meta-analysis, with a mean weight loss of 3.23kg (IC95 % -5.59 -0.86) after 16 weeks. Dietary-hygienic interventions are also effective in reducing cardiovascular risk. Other interventions such as omega-3 supplementation, vitamin D, N-acetylcysteine, and fasting have not proven to be effective. Comprehensive care programs have been developed to promote somatic care in psychiatric patients, such as the Canadian HeAL (Healthy Active Lives) program. These programs are more effective when proposed from the beginning of the disease and the introduction of antipsychotics. In this review, because there is no French recommendation, we translate a tool for the prescription of metformin and the Canadian recommendations from the HeAL program. Generalization of these programs to all young psychotic patients could improve their life expectancy and reduce the overall mortality. Prevention of cardiovascular risk factors and cardio-metabolic monitoring of treatments must be part of the standard of care in early psychosis. These programs aim at providing patients with the quality of somatic and mental care they are entitled to. This requires the involvement of all stakeholders, including patients and their families but also psychiatrists and other caregivers.

The effects of ghrelin on sleep, appetite, and memory, and its possible role in depression: A review of the literature.

OBJECTIVES: Ghrelin is an orexigenic digestive hormone that plays a role in sleep and memory. Our work aims is to synthesize the effects of ghrelin on appetite, sleep and memory, and also to evidence its role in depressive disorders. METHODS: A systematic search was carried out on PubMed with no time boundaries. The following MeSH terms were used: ghrelin AND (appetite regulation OR obesity), (sleep wake disorders OR sleep) (memory OR cognition disorders) (depression OR depressive disorder OR mood disorder). RESULTS: Ghrelin triggers appetite and alters meal patterns by making them longer and richer. This can lead to pathologies, obesity and insulin-resistance. Ghrelin seems to have a favourable effect on sleep in human beings. It tends to make sleep more efficacious and better quality. Finally, it seems to have an effect on synaptic plasticity in the zones involved in memory and it has been shown to improve memory capacity in rodents. Regarding depression, the administration of ghrelin leads to an anti-depressive effect in animals and in humans. Conversely, post anti-depressant ghrelin titrations have generally shown a decrease in ghrelin levels. Resistant patients seem to retain high levels. Finally, the seriousness of depression could be related to ghrelin levels. CONCLUSION: Ghrelin plays a probable part in depression, especially for particular endophenotypes. A better understanding of ghrelin in depression could potentially help to optimize future therapeutic treatments.

Do European Standard Disinfectant tests truly simulate in-use microbial and organic soiling conditions on food preparation surfaces?

AIMS: The results from European standard disinfectant tests are used as one basis to approve the use of disinfectants in Europe. The design of these laboratory-based tests should thus simulate as closely as possible the practical conditions and challenges that the disinfectants would encounter in use. No evidence is available that the organic and microbial loading in these tests simulates actual levels in the food service sector. METHODS AND RESULTS: Total organic carbon (TOC) and total viable count (TVC) were determined on 17 visibly clean and 45 visibly dirty surfaces in two restaurants and the food preparation surfaces of a large retail store. These values were compared to reference values recovered from surfaces soiled with the organic and microbial loading, following the standard conditions of the European Surface Test for bactericidal efficacy, EN 13697. CONCLUSIONS: The TOC reference values for clean and dirty conditions were higher than the data from practice, but cannot be regarded as statistical outliers. This was considered as a conservative assessment; however, as additional nine TOC samples from visibly dirty surfaces were discarded from the analysis, as their loading made them impossible to process. Similarly, the recovery of test organisms from surfaces contaminated according to EN 13697 was higher than the TVC from visibly dirty surfaces in practice; though they could not be regarded as statistical outliers of the whole data field. No correlation was found between TVC and TOC in the sampled data, which re-emphasizes the potential presence of micro-organisms on visibly clean surfaces and thus the need for the same degree of disinfection as visibly dirty surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: The organic soil and the microbial burden used in EN disinfectant standards represent a realistic worst-case scenario for disinfectants used in the food service and food-processing areas.

Saphenous nerve injury after anterior cruciate ligament reconstruction: Reduced numbness area after ligamentoplasty using quadriceps tendon compared with hamstring tendon.

PURPOSE: Injury to the infra-patellar branches of the saphenous nerve (IPBSN) is the main neurological complication of anterior cruciate ligament (ACL) reconstruction procedures. Surgical technique using quadriceps tendon (QT) autograft allows a less invasive tibial approach potentially protecting the IPBSN. The aim of this study was to compare the numbness surface of the cutaneous area supplied by the IPBSN after ACL reconstruction using either hamstring tendon (HT) or QT autografts. METHODS: This was a retrospective comparative cohort study including 51 patients who underwent ACL reconstruction (27 QT and 24 HT) between January 2017 and April 2018. A sensory clinical evaluation was performed on each patient: length of the tibial scar, eventual numbness surface area and the type of sensory disorder were reported. To be considered as an IPBSN lesion, the numbness area had to spread at least one-centimeter away from the scar. RESULTS: The average follow-up was 15 months. In the HT group, the numbness area surface measured 21.2 ± 19 cm2 (0-77) and the scar length was on average 31.3 ± 5.6 mm. In the QT group, the numbness area was reduced to 5 ± 10 cm2 (P = .0007) as well as the scar length (13.3 ± 2.8 mm, P < .0001). We counted five (17.8%) and 19 (76%) real IPBSN lesions in the QT and HT groups, respectively (P = .0002). Hypoesthesia was the main sensory disorder observed (87.5%). CONCLUSION: Numbness area of the cutaneous surface supplied by the IPBSN after ACL reconstruction is reduced using QT autograft compared with HT autograft.

Navigation for lower limb alignment during internal fixation of complex tibial-plateau fractures.

In complex fractures of the proximal tibial metaphysis and epiphysis, possible adverse outcomes after internal fixation include not only joint surface incongruity, but also lower limb malalignment requiring revision surgery. Navigation has been proven effective for the intraoperative control of lower limb alignment during osteotomy and knee arthroplasty. In complex traumatic fractures, temporary fixation by a locking screw plate allows sensor positioning followed by navigation maneuvers to adjust lower limb alignment. If malalignment is found, the construct can be modified economically by altering the diaphyseal fixation without modifying the metaphyseal screws. The objective of this study was to describe the use of navigation in three patients who required internal fixation of tibial-plateau fractures.

Meniscoplasty for lateral discoid meniscus tears: Long-term results of 14 cases.

INTRODUCTION: Discoid lateral meniscus lesions are relatively rare. The objective of this study was to determine the long-term results of 14 cases of discoid lateral meniscus tears treated by arthroscopic meniscoplasty between July 1991 and May 2009, and to assess the development of osteoarthritis in the lateral compartment. METHODS: The series consisted of 10 patients (14 knees): 3 girls under the age of 15, 3 men and 4 women aged from 16 to 47 years (mean age: 31.4±11.1 years). The main reason for consultation was pain in 10 cases, locking in 2 cases and pain associated with locking in 2 cases. The diagnosis was confirmed preoperatively by MRI in 10 cases, CT-arthrography in 1 case and arthrography in 3 cases. The indication for surgery was made because of a symptomatic discoid lateral meniscus. All cases were treated by arthroscopic meniscal reshaping. Functional results were evaluated using the Lysholm-Tegner, IKDC, KOOS and satisfaction scores. Radiological results were evaluated based on the modified Alhbäck classification for osteoarthritic (OA) changes. RESULTS: No complications were found. Two patients were lost to follow-up. The remaining eight patients (12 knees) were reviewed at a mean of 157.5±72.1 months (61-276). The mean Lysholm-Tegner score was 88.9±10.6 points (67-100), the mean KOOS was 92.4±9.5 (65-100) and the mean IKDC score was 85.4±16.5 points (65-100). All eight of the reviewed patients were satisfied or very satisfied with the result. Radiological analysis found that five knees had no signs of OA, five knees had stage 1, one had stage 2 and one had stage 3. At last follow-up, no patient had been reoperated. CONCLUSION: Meniscoplasty of discoid lateral meniscus tears leads to excellent long-term functional results despite signs of osteoarthritic changes in the lateral compartment of the knee. LEVEL OF EVIDENCE: IV (retrospective study).

Cationic phosphonolipids as nonviral gene transfer agents in the lungs of mice.

With the aim of developing new gene transfer tools for treating CF with gene therapy, we have synthesized a novel family of molecules named cationic phosphonolipids. The most efficient among them were selected by in vitro screening to compare their activities in vivo in mouse lungs. We used a reporter gene whose activity was measured cytofluorimetrically (FACS-Gal assay) and by means of a chemiluminescence technique. These tests allowed us to identify the percentage of transfected cells and to quantify total beta-galactosidase in the lungs. This enabled us to identify two molecules, significantly efficient in comparison with DNA alone: GLB73 (p = 0.0015) and GLB253 (p = 0.007). Their use resulted in a time lag between transfection and maximum efficiency: maximum efficiency was observed 4 days after transfection with GLB73, whereas it was noticeable only on day 7 with GLB253. Moreover, from toxicity studies carried out in vivo, GLB73 seems to be nontoxic. In vivo results were correlated with in vitro results obtained with CF epithelial cell lines. Consequently, GLB73 is a potential candidate for phase I clinical trials in humans.

Magnetic resonance imaging in juvenile rheumatoid arthritis.

OBJECTIVES: This study was undertaken to examine the role of magnetic resonance imaging (MRI) in the management of patients with juvenile rheumatoid arthritis (JRA). METHODS: A Medline search was performed to identify all publications pertaining to MRI in JRA. Further searches and identification of articles from bibliographies identified articles pertaining to plain radiograph imaging in JRA and MRI in adult rheumatoid arthritis. RESULTS: Studies in both children and adults have shown superiority of MRI to plain radiography in detecting synovial hypertrophy and articular cartilage abnormalities. Several studies in adults have shown a good correlation of MR images with gross anatomic as well as histological findings at arthroscopy. Biochemical changes that occur before structural changes within the joint may even be detectable with magnetic resonance spectroscopy. CONCLUSIONS: MRI holds promise for the assessment of disease progression in JRA and may be useful in serial evaluation, as in clinical trials.

The high signal intensity meniscus of the knee. Magnetic resonance evaluation and in vivo correlation.

This study describes the different appearances of meniscal abnormalities on magnetic resonance (MR) images and correlates macroscopic and histologic findings. Twenty-three of 40 cadaveric menisci with MR signal abnormalities were examined macroscopically; five of the 23 were studied histologically. In addition, MR studies of seven patients (14 menisci) were examined and findings were correlated arthroscopically. Histologic analysis was performed on two of these menisci. The two major findings on MR images were: (1) abnormal, high, centrally located signal intensity within the meniscus and (2) disruption of the peripheral meniscal contour. Macroscopically evident meniscal degeneration correlated well with findings on MR images in all cases. Histologic abnormalities included microcyst formation and separation of collagen bundles. Four menisci with intact outer contour lines on MR images had macroscopically identifiable tears. In addition, two meniscal tears were appreciated only after intra-articular injection of gadolinium-DTPA. We conclude that MR imaging is superior to macroscopic examination as performed by arthroscopy or arthrotomy for the detection of degenerative meniscal lesions. The technique also accurately identifies meniscal tears, a capability that might be enhanced by prior intra-articular injection of MR contrast agents.

The effect of intra-articular gadolinium-DTPA on synovial membrane and cartilage.

This investigation evaluated the potential effect of gadolinium (Gd)-DTPA-dimeglumine on synovial membrane and joint cartilage, using macroscopic, microscopic, and x-ray fluorescent spectroscopic techniques. Thirteen New Zealand white rabbits (26 knees) were used in this study, ten receiving 500 micromolar injections of Gd-DTPA-dimeglumine in their right knees; the remainder of the knees served as controls. One injected knee had minimal joint effusion and one had mild hyperemia. Microscopically four knees exhibited mild focal hyperplasia of the synovium, another three minimal focal mononuclear cell infiltration. X-ray fluorescent spectroscopy demonstrated no evidence of Gd-DTPA-dimeglumine in the synovium or articular cartilage. Neither macroscopic nor microscopic evaluation detected any Gd-DTPA-dimeglumine related effects. Gd-DTPA-dimeglumine was found to be safe for intra-articular injection in this animal model.

Phosphonocationic lipids in protein delivery to mice lungs.

Cationic liposomes constitute one of the main approaches currently investigated to introduce a gene with therapeutic properties into a cell. Another alternative consists in directly introducing the normal protein of concern to, for example, restore the deleted function. We report here on in vitro and in vivo results obtained with GLB73, one of the phosphonolipids investigated as gene transfer agents. In previous studies this cationic lipid had shown its DNA-transfer efficacy in vitro and in vivo. We also confirmed the feasibility of protein/cationic lipid delivery in epithelial cells of mice lungs after intratracheal administration by use of a reporter gene (beta-galactosidase). Two quantitative tests (i.e., a chemiluminescent assay and a flow cytometry assay) were used to determine the amount of beta-galactosidase found in the lungs and the percentage of transfected cells. They showed that 50% of the cells of mice lungs were still positive at day 4 after protein/GLB73 delivery. Immunohistochemistry and electron microscopy studies allowed us to determine the spatial distribution and visualize the penetration of our complex into the lungs.

What is the surface specific area of porous cement-based material? A nuclear magnetic relaxation dispersion approach.

We propose a new NMR method to measure and follow the evolution of the surface specific area, Sp, of a porous cement-based material. This method, that does not require any preliminary drying process, uses nuclear magnetic relaxation dispersion (NMRD), the measurement of spin-lattice relaxation rate as a function of magnetic field strength or nuclear Larmor frequency. The method is applied for three different mortars samples prepared by mixing cement, sand, silica fume, water and superplasticizer with a water to cement ratio w/c=0.25, 0.38 and 0.65, respectively. The evolution of Sp grows linearly with the degree of advancement of chemical reactions measured by thermal heating and we evidence two relaxation processes independent of the w/c ratio.

Variability of sperm specific histones in sea urchins.

The variability of sperm histones was compared in two species of sea urchin. Whole sperm specific histones (SpH), were isolated from Tetrapygus niger (Arbacoida) and Parechinus angulosus (Echinoida). Individual histones were purified by chromatography on BioGel P-60 followed by reverse high pressure liquid chromatography (HPLC). The heterogeneity of each major histone type from T. niger was established from their HPLC elution patterns and further confirmed by electrophoresis in polyacrylamide gels containing 6 mM Triton X-100 combined with a transverse urea gradient (0--8 M). In T. niger, as well as in P. angulosus, a single form of SpH1 and SpH2A were found. In contrast, SpH2B was found to be heterogeneous, but represented by one major form in both species. The relatedness between both sets of histones was determined by establishing their immunological cross-reactivity. In this context, polyclonal antibodies elicited against T. niger sperm histones were assayed against individual histones from P. angulosus. From the results obtained, it emerged that histone SpH2A was the more closely related protein between these two species, followed by histone SpH1. In contrast, histone SpH2B was found to be only moderately related. These results confirm that SpH2A did not co-evolve with SpH2B, as was predicted for most species.

Combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia for hip fractures in the elderly.

BACKGROUND AND OBJECTIVES: This prospective randomized study was designed to determine the hemodynamic effects and quality of combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia in the elderly for repair of proximal femoral fractures. METHODS: Twenty-nine elderly patients ranging in age from 68 to 97 years were randomly assigned to 2 groups: a spinal anesthesia group with single-shot 3 mL 0.5% plain bupivacaine, and a combined block group with 30 mL lidocaine 1.33% with epinephrine for the posterior lumbar plexus block and 10 mL same mixture for the parasacral block and an iliac crest block with 5 mL lidocaine 1%. RESULTS: No need for general anesthesia was encountered in either group. Anesthesia was judged unsatisfactory in 1 of 15 patients in the combined block group. The initial decrease of mean arterial pressure was 38% in the spinal group and 27% in the block group and was not significantly different. A more prolonged hemodynamic effect was found in the spinal group, indicated by the more frequent use of ephedrine to stabilize blood pressure (P<.05). Patients over 85 years had a significantly larger decrease in blood pressure than younger patients (P<.01). CONCLUSIONS: Plain bupivacaine spinal anesthesia and combined lumbar/sacral plexus block provided adequate anesthesia for repair of hip fracture in the elderly. Hypotension was induced by both the combined peripheral nerve block and plain bupivacaine spinal anesthesia in aged patients; hypotension was found to be longer lasting after spinal anesthesia and of a larger magnitude in patients over 85 years of age.

Post-synchronized scintigraphic data to estimate antral motility.

We evaluated an improved dynamic antral scintigraphy (DAS) technique, without any frequency filtering or computation of an autocorrelation function. This DAS was performed in 15 consecutive patients and 10 healthy volunteers. Antral frequency was first estimated and was given as an input parameter to compute phase and amplitude values in each antral pixel. Motility indices were calculated by multiplying the frequency by a normalized amplitude in the whole antrum. In addition, a gastric emptying (GE) test was performed. Only 10 patients had a delayed GE when using a cut-off value of the mean of half emptying time (T +2SD) obtained in controls. Antral frequencies were significantly increased but motility indices were significantly lower in patients than in controls. These results in patients were accounted for by a retention of food in the antrum. Therefore, amplitude normalization by the antral mean count activity of each set of data was essential for discriminating between patients and controls and normalized indices appeared early predictors of hypomotility in patients with normal GE. This improved DAS technique should be a useful tool to assess antral dysmotility noninvasively, and may be of physiological and clinical interest.

MR imaging of pediatric musculoskeletal inflammatory and infectious disorders.

Inflammatory and infectious disorders of the skeletally immature extraspinal musculoskeletal system affect the bones, contiguous soft tissues, muscles, and joints. MR imaging of osteomyelitis, soft tissue infection, inflammatory muscle disease, and acute and chronic joint disease are discussed in the context of underlying pathophysiology. Discussion includes imaging optimization, contribution of MR imaging to overall patient management, and differential diagnostic considerations for the pediatric patient.

[Three-dimensional reconstruction calibrated with ultrasonographic images. Application to the measurement of clot volume in vitro]. / Reconstruction tridimensionnelle calibrée à partir d'images ultrasonographiques. Applications à la mesure volumique des caillots in vitro.

OBJECTIVE: We used 3D ultrasonographic reconstruction with manual acquisition to study the volume of venous clots in vitro. MATERIAL AND METHODS: Native 2D ultrasound slices were acquired free hand for 3D reconstruction. The spatial coordinates of each slice were delivered in real time with an electromagnetic captor. We applied a standard ultrasound protocol to test the calibrated 3D reconstruction quantitatively. The volume of 5 clots of increasing size was quantified in vitro using manual segmentation in a double-blind manner by two independent operators. RESULTS: The comparison tests and the interoperator regression lines evidenced good agreement between real and measured volumes, confirming the coherence of the reconstruction protocol and the feasibility of this technique in a routine medical setting. Intraoperator variability was 7 to 11% and interoperator variability 16.9%. CONCLUSION: This calibrated 3D reconstruction is compatible with in vitro measurement of venous clots. This technique could be useful to follow the evolution of the head of proximal deep vein thrombi in vivo. It will be more reliable with semi-automatic or even automatic segmentation becomes available.

V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors.

The v-erbA oncogene transforms chicken erythrocytic progenitors (T2EC) by blocking their differentiation and freezing them in a state of self-renewal. Transcriptomes of T2EC, expressing either v-erbA or a non-transforming form of v-erbA (S61G), were compared using serial analysis of gene expression and some, but not all, mRNA-encoding ribosomal proteins were seen to be affected by v-erbA. These results suggest that this oncogene could modulate the composition of ribosomes. In the present study, we demonstrate, using two-dimensional difference in gel electrophoresis, that v-erbA-expressing cells have a lower amount of RPL11 associated with the ribosomes. The presence of ribosomes devoid of RPL11 in v-erbA-expressing cells was further confirmed by immunoprecipitation. In order to assess the possible impact of these specialized ribosomes on the translational activity, we analyzed proteomes of either v-erbA or S61G-expressing cells using 2D/mass spectrometry, and identified nine proteins present in differing amounts within these cells. Among these proteins, we focused on HSP70 because of its involvement in erythroid differentiation. Our results indicate that, in v-erbA-expressing cells, hsp70 is not only transcribed but also translated more efficiently, as shown by polyribosome fractionation experiments. We demonstrate here, for the first time, the existence of ribosomes with different protein components, notably ribosomes devoid of RPL11, and a regulation of mRNA translation depending on v-erbA oncogene expression.