Upon heat stress processing of ribosomal RNA precursors into mature rRNAs is compromised after cleavage at primary P site in Arabidopsis thaliana.

Transcription and processing of 45S rRNAs in the nucleolus are keystones of ribosome biogenesis. While these processes are severely impacted by stress conditions in multiple species, primarily upon heat exposure, we lack information about the molecular mechanisms allowing sessile organisms without a temperature-control system, like plants, to cope with such circumstances. We show that heat stress disturbs nucleolar structure, inhibits pre-rRNA processing and provokes imbalanced ribosome profiles in Arabidopsis thaliana plants. Notably, the accuracy of transcription initiation and cleavage at the primary P site in the 5'ETS (5' External Transcribed Spacer) are not affected but the levels of primary 45S and 35S transcripts are, respectively, increased and reduced. In contrast, precursors of 18S, 5.8S and 25S RNAs are rapidly undetectable upon heat stress. Remarkably, nucleolar structure, pre-rRNAs from major ITS1 processing pathway and ribosome profiles are restored after returning to optimal conditions, shedding light on the extreme plasticity of nucleolar functions in plant cells. Further genetic and molecular analysis to identify molecular clues implicated in these nucleolar responses indicate that cleavage rate at P site and nucleolin protein expression can act as a checkpoint control towards a productive pre-rRNA processing pathway.

Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in L-Dopa-Induced Dyskinesia.

Using bacterial artificial chromosome-double transgenic mice expressing tdTomato in D1 receptor-medium spiny neurons (MSNs) and enhanced green fluorescent protein in D2 receptor-MSNs, we have studied changes in spine density and perisomatic GABAergic boutons density in MSNs of both the D1R and D2R pathways, in an experimental model of parkinsonism (mouse injected with 6-hydroxydopamine in the medial forebrain bundle), both in the parkinsonian and dyskinetic condition induced by L-DOPA treatment. To assess changes in perisomatic GABAergic connectivity onto MSNs, we measured the number of contacts originated from parvalbumin (PV)-containing striatal "fast-spiking" interneurons (FSIs), the major component of a feed-forward inhibition mechanism that regulates spike timing in MSNs, in both cell types as well as the number of vesicular GABA transporter (VGAT) contacts. Furthermore, we determined changes in PV-immunoreactive cell density by PV immunolabeling combined with Wisteria floribunda agglutinin (WFA) labeling to detect FSI in a PV-independent manner. We also explored the differential expression of striatal activity-regulated cytoskeleton-associated protein (Arc) and c-Fos in both types of MSNs as a measure of neuronal activation. Our results confirm previous findings of major structural changes in dendritic spine density after nigrostriatal denervation, which are further modified in the dyskinetic condition. Moreover, the finding of differential modifications in perisomatic GABAergic connectivity and neuronal activation in MSNs suggests an attempt by the system to regain homeostasis after denervation and an imbalance between excitation and inhibition leading to the development of dyskinesia after exposure to L-DOPA.

APOBEC3A intratumoral DNA electroporation in mice.

Human APOBEC3A (A3A) cytidine deaminase shows pro-apoptotic properties resulting from hypermutation of genomic DNA, induction of double-stranded DNA breaks (DSBs) and G1 cell cycle arrest. Given this, we evaluated the antitumor efficacy of A3A by intratumoral electroporation of an A3A expression plasmid. DNA was repeatedly electroporated into B16OVA, B16Luc tumors of C57BL/6J mice as well as the aggressive fibrosarcoma Sarc2 tumor of HLA-A*0201/DRB1*0101 transgenic mice using noninvasive plate electrodes. Intratumoral electroporation of A3A plasmid DNA resulted in regression of ~50% of small B16OVA melanoma tumors that did not rebound in the following 2 months without treatment. Larger or more aggressive tumors escaped regression when so treated. As APOBEC3A was much less efficient in provoking hypermutation and DSBs in B16OVA cells compared with human or quail cells, it is likely that APOBEC3A would be more efficient in a human setting than in a mouse model.

[Pneumocystis jirovecii pneumonia in non-HIV infected patients: a study of 41 cases]. / Pneumocystose pulmonaire chez des patients immunodéprimés non infectés par le VIH : étude de 41 cas.

BACKGROUND: The increasing use of immunosuppressive and cytotoxic therapies leads to a growing number of opportunistic infections especially Pneumocystis jirovecii pneumonia (PCP). The purpose of our study was to describe the population involved, and to assess clinical, biological, and mortality data. METHODS: We collected retrospectively the whole medical file of all PCP cases diagnosed in non-HIV infected patients, in two French University Hospitals in the last decade (1999-2009). Diagnosis was made on standard coloration and/or immunofluorescence analysis of bronchoalveolar lavage fluid (BAL). RESULTS: Forty-one patients were included in the study, mean age 56 (±12.5) years, sex ratio 0.71 men/woman. Underlying diseases were as follow: 12 patients (29%) were renal transplant recipients, 13 (32%) were treated for solid cancers, and 16 (39%) suffered from various diseases (three allogenic bone-marrow transplantation, 11 hematological malignancies, one pulmonary transplantation, one vasculitis). Twelve patients died (i.e. 29%). Median lymphocyte count was 542/mm(3). More than 85% patients received corticosteroids at a median cumulative 6-month dose of 2700mg. Seven patients (17%) had a PCP prophylaxis. Clinical worsening at day 5 (P<0.003), poor control of the underlying disease (P<0.015), WHO performans status superior than 2 (P<0.025), high temperature (P<0.04), and high oxygen flow (P<0.042) were linked to a poor prognosis. DISCUSSION/CONCLUSION: The prognosis factors found are mostly linked to the patients' clinical severity. We would like to highlight: first, near to 30% mortality rate, secondly, a lack of prophylaxis in 34 patients, reflecting the difficulty to define PCP's risk in non HIV-infected patients.

[B-type natriuretic peptide levels and renal function in the diagnosis of heart failure in the elderly]. / Influence de la fonction rénale sur la pertinence diagnostique du BNP chez l'insuffisant cardiaque âgé.

AIM OF THE STUDY: BNP levels are accurate in the diagnosis of heart failure and useful in clinical practice. Relationship between BNP, heart failure (HF) and renal function are little known in the elderly. Renal function influence the optimal cut point of BNP in patients with a Glomerular Filtration Rate (eGFR) lesser than 60 ml/min/1.73 m(2). METHODOLOGY: A total of 71 patients (mean age = 85 years) were admitted in a Cardiogeriatric Unit. We noted several parameters, age, gender, the presence or the absence of Systolic Heart Failure (clinical history and physical examination), the echographic measure of the left ventricular ejection fraction, the eGFR value calculated by simplified MDRD formula and the BNP value. We divided these patients into six groups according the presence of HF and eGFR value higher than 60ml/min/1.73m(2),or between 30 and 60 or between 15 and 30. RESULTS: Our results show that the BNP value is higher in all the three groups of patients with Heart Failure with or without diminution of the eGFR: for example, 1220 pg/ml in the presence of HF versus 788 pg/ml in the absence of HF in the two groups with the eGFR is calculated between 15 and 30 ml/min/1.73m(2). CONCLUSION: BNP is a helpful tool in clinical practice for the diagnosis of Systolic Heart Failure in the presence of renal impairment in the elderly with a higher biomarker cut point.

[Prognostic value of the B-type natriuretic peptide (BNP) in a cardiogeriatric department]. / Expérience de la valeur pronostique du BNP à l'admission en cardiogériatrie.

UNLABELLED: BNP levels are quantitative biomarkers of heart failure (HF), with accuracy in the diagnosis, prognosis of HF, and improve patient management in emergencies. But specific studies are necessary in the very elderly because of the lack of data. To access how BNP predicts immediate prognosis, we have included 167 inpatients (mean age=83 years) at their hospital admission with systematic blood measure of BNP by Biosite Assay and we divided these patients into three groups, according to BNP level: (1) normal BNP level less than 100 pg/ml; (2) BNP level in the grey zone: 100 to 300 pg/ml; (3) increased BNP level greater than 300 pg/ml. Cardiovascular mortality has been compared in these three groups of patients and results showed a significant increase of mortality in the two groups 2 and 3, when the BNP value was higher than 100 pg/ml. CONCLUSION: As a quantitative marker of HF, the use of BNP levels with a cut point of 100 pg/ml is helpful for prognosis evaluation in the elderly.

[Hypertensive emergencies]. / Les urgences hypertensives.

Hypertensive urgencies are common clinical occurrences in hypertensive patients. The definition of hypertensive urgencies (target blood pression) were not consistent, but involved often target end-organ damage in emergencies. Epidemiology and physiopathology are briefly described. Treatment practices of hypertensive crisis were difficult because of the lack of evidence supporting the use of one therapeutic agent over another and its posology.

[Application of guidelines concerning systolic hypertension in patients over 80 years of age: experience in a geriatric institute]. / Application des recommandations dans l'hypertension artérielle systolique après 80 ans: expérience en institution gériatrique.

Application of the guidelines concerning systolic hypertension in patients over 80 years of age: experience in a geriatric institute In order to compare the blood pressures of elderly hypertensive patients treated in accordance with recent guidelines, the authors measured the casual blood pressure of a population of long stay patients. Recent data from the FRAMINGHAM HEART STUDY shows that, in the general population, only 23% of women over 80 years of age attained the target values, a blood pressure less than 140/90 mmHg, and only 35% of those treated for hypertension. Eighty patients in the long stay unit of Allauch Hospital were studied in this transverse study performed from the 23rd to 25th of August 2005. The blood pressure (SBP, DBP and PP) and heart rate at consultation were measured by the same physician with the same sphygmomanometer (OMRON M4). The prescribed antihypertensive medication was noted; the presence of atrial fibrillation and the echocardiographic data including left atrial (LA) diameter in M-mode were also included. Forty-four of the 80 patients included were hypertensive (84% women, average age 88.7 years; 16% men, average age 86 years) and treated with the same objective of blood pressure (BP < 140/90 mmHg). The patients were treated by monotherapy in 6% of cases, bitherapy in 27% of cases, tritherapy in 6.8% of cases, and quadritherapy in 4.5% of cases. The distribution of antihypertensive agents in the patients over 80 years of age was almost identical to that of the ninety years of age group. The target blood pressure was attained in 67.5% of women and 71.5% of men. The incidence of atrial fibrillation in the hypertensive patients over 80 years of age was 32%, and 85.7% of them had dilated left atrium (>40 mm). The authors conclude that target blood pressures were more often attained (68% vs. 35%) in this Geriatric Institute than in the American general population probably because of environmental and motivational reasons, including those of the medical staff.

Outbreak of Clostridium difficile-related diarrhoea in an adult oncology unit: risk factors and microbiological characteristics.

We describe the risk factors and microbiological findings of an outbreak of Clostridium difficile (CD)-related diarrhoea in the Medical Oncology Department of the Curie Institute. Screening for CD in stools was performed on 59 patients with diarrhoea and 146 patients without diarrhoea. Toxin secretion, serotyping (enzyme-linked immunosorbant assay) and genotyping (AP-polymerase chain reaction) were performed on 39 CD strains from 32 patients. The risk factors for toxigenic CD-positive diarrhoea were also investigated. Twenty-seven (46%) patients with diarrhoea and 12 (8%) patients without diarrhoea were CD-positive (P<0.001). Patients with diarrhoea were older (P=0.03). Chemotherapy was a risk factor for toxigenic CD-related diarrhoea (P=0.02) and antibiotic treatment was a risk factor only in those patients who were also receiving chemotherapy. Serotyping and genotyping showed that several strains were involved in this outbreak, with only two instances of patient-to-patient transmission, involving four and two patients.

[Biological factors of PTSD: neurotransmitters and neuromodulators]. / Facteurs biologiques du stress post-traumatique: neurotransmission et neuromodulation.

Subjects with posttraumatic stress disorder exhibit abnormalities in many psychobiological systems. Studies of the effects of stress on learning and memory processes suggest that fear conditioning, behavioural sensitisation, and a failure of extinction may be important in the persistence and reexperiencing of traumatic memories and stress sensitivity. All these symptoms are supported by specific biological mechanisms including NMDA receptors, noradrenergic system, etc. Recent findings show that amino acid transmitters, glutamate and GABA, are intimately involved in the process of factual memory registration, and suggest that amine neurotransmitters, norepinephrine and serotonin, are involved in encoding emotional memory. In addition, research suggests that 5-HT neurones have directs effects on both adrenergic and HPA function. Such findings provide important information that should guide current pharmacological practice and the development of innovative biological therapeutics.

Validity of earlier positivity of central venous blood cultures in comparison with peripheral blood cultures for diagnosing catheter-related bacteremia in cancer patients.

We carried out a prospective study in two French Comprehensive Cancer Centers (95 and 184 beds, respectively) to assess the validity of a test based on the earlier positivity of central venous blood cultures in comparison with peripheral blood cultures for predicting catheter-related bacteremia. The differences between the times to positivity for the 21 patients with clinical catheter-related bacteremia and the differences between the times to positivity for the nine patients with bacteremia due to another source were compared by the median test. The difference between the median values was significant (P = 0.0003). A receiver operating characteristic curve was constructed to determine the optimum threshold of the test, which appeared to be at the cutoff point of >/=+3 h, with 100% specificity and 81% sensitivity. The positive and negative predictive values obtained with this cutoff point confirmed the efficacy of the test for predicting the presence or absence of catheter-related bacteremia in cancer patients. The cutoff point was then used to post-classify the 68 episodes of bacteremia from an unknown source. The characteristics and clinical course of both the positive and negative post-classified episodes did not show that the test was clearly useful for a large number of clinical presentations. We therefore suggest restricting it to febrile neutropenic cancer patients for whom clinical signs of infection are slight or absent and when the test is positive.

[Infection and cancer: general information and specific questions]. / Infection et cancer: notions générales et questions actuelles.

The main risk factors of infectious complications in cancer patients result from immune deficiency more or less related to cancer. Prognosis is related to the type and grade of the underlying disease. Prospective studies should be conducted to update data on the frequency of infections, morbidity and mortality (expert agreement). Prospective studies are needed to follow the epidemiology in cancer patients, particularly in neutropenic patients (expert agreement). Prospective studies should be conducted to determine prognosis factors allowing precise recognition of "low-risk" neutropenic patients with fever who could benefit from home care (expert agreement). When infection is suspected, the first criterion determining the therapeutic attitude concern signs of gravity requiring emergency care (septic shock). Beyond this situation, the first criterion determining the therapeutic attitude is the severity of the neutropenia. Microbial diagnosis is essential for initiating and later adapting anti-infectious treatment as well as for assessing efficacy.

[Polysomnographic aspects of antidepressive therapy]. / Aspects polysomnographiques des thérapeutiques antidépressives.

Sleep disorders are very common in depression. They have been quantitatively and qualitatively described by polysomnographical recordings. It is of interest to know how treatments act on polysomnographical data. In this article, we propose to evaluate five treatment approaches proposed for depressive illness. Pharmacological treatment induces marked changes in sleep continuity, sleep architecture and REM sleep. However, no specific sleep profiles emerge neither for each treatment class nor for molecules within the same pharmacological class. But actually, sleep data cannot be viewed as markers of treatment response. Psychotherapeutic interventions have only few effects on sleep of depressed patients. Treatment efficiency does not seem to be correlated to abnormal sleep parameters. Sleep deprivation induces marked changes in nearly all sleep parameters and in temporal distribution of sleep stages during the night. Actually, the efficiency of sleep deprivation cannot longer be explained by suppression of REM sleep. Sleep deprivation has only a transient effect and treatment indications are therefore secondary. Sleep parameters do not distinguish responders from non-responders. Sleep deprivation shows that there is a depressogenic effect of sleep in the end of the night. Bright light therapy shows marked changes in sleep continuity parameters. Among all studies that examine the impact of treatment on sleep EEG, ECT has received little attention. The few studies available are either case studies or with poor effectifes++. For this reason and because of methodological bias, results are heterogeneous and no definite conclusions can be drawn. But all of them agree that ECT modifies sleep EEG. So, changes in polysomnographical data cannot predict response to any treatment. Prospective sleep studies are difficult to realise on a great number of patients explaining absence of treatment predictors.

[Standards, options and recommendations for good practice in hemoculture in cancerology]. / Standards, Options et Recommandations pour une bonne pratique des hémocultures en cancérologie.

Excepting emergency and aplasia: two to three blood samples should be draw for culture an hour apart within a 24 period (standard). For emergency or aplasia: two to three blood samples should be drawn for culture before initiating early antibiotic therapy. The delay between samples drawn from different sites should be less than one hour (standard). For patients on antibiotics: four to six blood samples should be drawn for culture within 48 hours, outside ongoing antibiotic administration. If the patient is given corticosteroids, it is recommended to draw two or three blood samples in case of deterioration (agreement of the experts). Rigorous aseptic techniques must be used (standard). Culture media are chosen according to the institution's microbial ecology (standard). The volume of blood drawn should be adapted to the system used (standard). Culture positivity is determined at 24 to 48 hours.

[Standards, Options and Recommendations (SOR) for the surveillance and the prevention of cross infections in oncology. Fédération Nationale des Centres de Lutte Contre le Cancer]. / Standards, Options et Recommandations (SOR) pour la surveillance et la prévention des infections nosocomiales en cancérologie.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the prevention and the surveillance of cross infection in oncology. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 106 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: 1) Criteria of infection status and nosocomiality defined by the Centers for Infectious Diseases (CDC) and Prevention and the Superior Council of Public Hygiene (CSHPF) are not adapted and have to be redefined in oncology. 2) The epidemiology of nosocomial infections in oncology is not well known but their incidence seems to be higher. Numerous risk factors of cross infections coexist in cancer patients, among which the duration and depth of neutropenia. 3) Surveillance and prevention of cross infection are compulsory and were taken into account in the accreditation of hospitals. Obligation is expressed in terms of means and results. 4) The objectives of the cross infection surveillance are to detect major problems and critic situations, to guide probabilistic antibiotic therapy and to assess the effectiveness of the infections control. The surveillance means consist in prevalence and incidence survey, punctually and continuously conducted. 5) The three specific behaviors to be adopted to prevent cross infections are to control: all the patients, infected patients carrying multiresistant bacteria, immunodepressed patients. 6) Standards of care have to be applied to a/l patients with cancer. 7) It is necessary to add particular septic cares for the patients infected with micro-organisms indicated on reference lists or carrying multiresistant bacteria. 8) The only objective of the protective isolation of immunodepressed cancer patients is to reduce the cross infection. There is no standard behavior for the indications and the modalities of protective isolation. The prevention behaviors to be taken are defined by expert agreements.

[Biological factors of post-traumatic stress: neuroendocrine aspects]. / Facteurs biologiques du stress post-traumatique: aspects neuroendocriniens.

The core symptoms of post-traumatic stress disorder (PTSD) include persistent reexperiencing of the traumatic event, avoidance of stimuli associated with the trauma, and autonomic hyperarousal. Many neurotransmitter systems and neurobiologic mechanisms may account for these primary symptoms of PTSD. Severe psychological trauma results in the parallel activation of these systems, producing an array of adaptive behavioral and physiologic responses necessary for survival. The pathophysiology of PTSD may involve dysfunction of several brain structures, particularly the amygdala, locus coeruleus, and hippocampus, as well as noradrenergic system and hypothalamic-pituitary-adrenal (HPA) axis. The neuroendocrinology of PTSD, and specifically hypothalamic-pituitary-adrenal axis alterations, are ways of examining biologic heterogeneity following trauma and its possible clinical implications. The decreased levels of cortisol, the increased responsiveness of glucocorticoid receptors, the increased sensitivity of the HPA negative feedback inhibition and its progressive sensitization are the neuroendocrine alterations specifically associated with the development of PTSD.

[Sleep electroencephalography in depression and mental disorders with depressive comorbidity]. / La valeur de la polysomnographie dans la dépression et les pathologies mentales avec comorbidité dépressive.

Traditional scoring of sleep EEG in depressed patients shows abnormalities in sleep maintenance, sleep architecture, REM sleep, the distribution of slow wave and REM sleep during the night. Computerized analysis that comprises the period-amplitude analysis procedure and spectral analysis discloses changes in delta activity and distribution of delta activity. However, these methods of analysing EEG sleep are not able to distinguish the various concepts of depression: endogenous and non-endogenous depression, unipolar and bipolar depression, psychotic and non-psychotic depression. Polysomnographical data in patients with recurrent depression show alteration during remission suggesting trait-like abnormalities of sleep in depression illness. Shortened REM latency is not specific in depression. This sleep parameter is defined in many different ways explaining the heterogeneousness of study results and the failure of constituting a biological marker. Many sleep parameters are affected by several factors such as age, gender and severity. Several physiopathological hypotheses have been proposed to explain EEG sleep alterations. They refer either to circadian rhythms such as the two process model of Borbély, the phase advance hypothesis and the circadian amplitude hypothesis, or to neurotransmitter abnormalities such as the cholinergic hypothesis. None of them takes sufficient account of all the sleep abnormalities. Sleep abnormalities have also been described in other psychiatric disorders such as mania, panic and obsessional-compulsive disorders, generalized anxiety, phobias, post-traumatic stress disorder, eating disorders, borderline personality, schizophrenia and dementia. None of them have a particular sleep EEG profile which allows to differentiate between them. A concomitant episode of major depression cannot be uncovered by sleep recordings.

[Atypical depression]. / Dépressions atypiques.

The principal atypical aspects of depressive disease are: minor and attenued aspects, monosymptomatic and atypical aspects (food disorders and sleep disorders), masqued aspects (somatoform, anxious, characterial and addict disorders), atypical aspects of child (anxious nevrotical disorder), pseudo-demented and characterial aspects of aged subjects. Facing to these aspects, the diagnosis of depression is evoqued on: the recent and fast advent of these disorders, their morning predominance, their recurrent character, the state of attenued depressive symptoms (anhedonia), the positive responsiveness to treatment.