The Montreal Cognitive Assessment (MoCA) with a double threshold: improving the MoCA for triaging patients in need of a neuropsychological assessment.

OBJECTIVES: Diagnosis of patients suspected of mild dementia (MD) is a challenge and patient numbers continue to rise. A short test triaging patients in need of a neuropsychological assessment (NPA) is welcome. The Montreal cognitive assessment (MoCA) has high sensitivity at the original cutoff <26 for MD, but results in too many false-positive (FP) referrals in clinical practice (low specificity). A cutoff that finds all patients at high risk of MD without referring to many patients not (yet) in need of an NPA is needed. A difficulty is who is to be considered at risk, as definitions for disease (e.g. MD) do not always define health at the same time and thereby create subthreshold disorders. DESIGN: In this study, we compared different selection strategies to efficiently identify patients in need of an NPA. Using the MoCA with a double threshold tackles the dilemma of increasing the specificity without decreasing the sensitivity and creates the opportunity to distinguish the clinical (MD) and subclinical (MCI) state and hence to get their appropriate policy. SETTING/PARTICIPANTS: Patients referred to old-age psychiatry suspected of cognitive impairment that could benefit from an NPA (n = 693). RESULTS: The optimal strategy was a two-stage selection process using the MoCA with a double threshold as an add-on after initial assessment. By selecting who is likely to have dementia and should be assessed further (MoCA<21), who should be discharged (≥26), and who's course should be monitored actively as they are at increased risk (21<26). CONCLUSION: By using two cutoffs, the clinical value of the MoCA improved for triaging. A double-threshold MoCA not only gave the best results; accuracy, PPV, NPV, and reducing FP referrals by 65%, still correctly triaging most MD patients. It also identified most MCIs whose intermediate state justifies active monitoring.

Characterisation of black skin stratum corneum by digital macroscopic images analysis.

Black skin medical images generally show very low contrast. Being in a global initiative of characterisation of black skin horny layer (stratum corneum) by digital images analysis, the authors in this study proposed a four-step approach. The first step consists of differentiation between probable healthy skin regions and those affected. For that, they used an automatic classification system based on multilayer perceptron artificial neural networks. The network has been trained with texture and colour features. Best features selection and network architecture definition were done using sequential network construction algorithm-based method. After classification, selected regions undergo a colour transformation, in order to increase the contrast with the lesion region. Thirdly, created colour information serves as the basis for a modified fuzzy c-mean clustering algorithm to perform segmentation. The proposed method, named neural network-based fuzzy clustering, was applied to many black skin lesion images and they obtained segmentation rates up to 94.67%. The last stage consists in calculating characteristics. Eight parameters are concerned: uniformity, standard deviation, skewness, kurtosis, smoothness, entropy, and average pixel values calculated for red and blue colour channels. All developed methods were tested with a database of 600 images and obtained results were discussed and compared with similar works.

[Assessment before surgical treatment for pelvic organ prolapse: Clinical practice guidelines]. / Bilan avant le traitement chirurgical d'un prolapsus génital : Recommandations pour la pratique clinique.

INTRODUCTION: The issue addressed in this chapter of recommendations is: What is the clinical and para-clinical assessment to achieve in women with genital prolapse and for whom surgical treatment has been decided. What are the clinical elements of the examination that must be taken into account as a risk factor of failure or relapse after surgery, in order to anticipate and evaluate possible surgical difficulties, and to move towards a preferred surgical technique? MATERIAL AND METHODS: This work is based on a systematic review of the literature (PubMed, Medline, Cochrane Library, Cochrane Database of Systemactic Reviews, EMBASE) for meta-analyzes, randomized trials, registries, literature reviews, controlled studies and major not controlled studies, published on the subject. Its implementation has followed the methodology of the HAS on the recommendations for clinical practice, with a scientific argument (with the level of evidence, NP) and a recommendation grade (A, B, C, and professional agreement [AP]). RESULTS: It suits first of all to describe prolapse, by clinical examination, helped, if needed, by a supplement of imagery if clinical examination data are insufficient or in case of discrepancy between the functional signs and clinical anomalies found, or in case of doubt in associated pathology. It suits to look relapse risk factors (high grade prolapse) and postoperative complications risk factors (risk factors for prothetic exposure, surgical approach difficulties, pelvic pain syndrome with hypersensitivity) to inform the patient and guide the therapeutic choice. Urinary functional disorders associated with prolapse (urinary incontinence, overactive bladder, dysuria, urinary tract infection, upper urinary tract impact) will be search and evaluated by interview and clinical examination and by a flowmeter with measurement of the post voiding residue, a urinalysis, and renal-bladder ultrasound. In the presence of voiding disorders, it is appropriate to do their clinical and urodynamic evaluation. In the absence of any spontaneous or hidden urinary sign, there is so far no reason to recommend systematically urodynamic assessment. Anorectal symptoms associated with prolapse (irritable bowel syndrome, obstruction of defecation, fecal incontinence) should be search and evaluated. Before prolapse surgery, it is essential not to ignore gynecologic pathology. CONCLUSION: Before proposing a surgical cure of genital prolapse of women, it suits to achieve a clinical and paraclinical assessment to describe prolapse (anatomical structures involved, grade), to look for recurrence, difficulties approach and postoperative complications risk factors, and to appreciate the impact or the symptoms associated with prolapse (urinary, anorectal, gynecological, pelvic-perineal pain) to guide their evaluation and their treatment. © 2016 Published by Elsevier Masson SAS.

[Emil Kraepelin: a pioneer of modern psychiatry. On the occasion of the hundred and fiftieth anniversary of his birth]. / Emil Kraepelin: un pionnier de la psychiatrie moderne (à l'occasion du cent cinquantième anniversaire de sa naissance).

Emil Kraepelin (1856-1926) whose hundred and fiftieth birth anniversary we are celebrating this year, is one of the most renowned figures of psychiatry. His Memoirs published in 1983 provide insight on the individual. In his early career he lived in Würzburg, Munich, Leipzig, Leubus, Dresden, and then in Dorpat in 1886 (as visiting professor) where he stayed for five years, in Heidelberg (as regular professor) from 1891 to 1904, and lastly in Munich. Kraepelin ranks among the great clinical medicine forerunners who followed in Kahlbaum's footsteps. For him, the foremost task of scientific psychiatry was to circumscribe pathological entities. At the foundation of Kraepelin-inspired scientific psychiatry lies the notion of the <> of disease, as opposed to the <> approach (5th edition of the Treatise), whereby it is no longer concerned with the study of mental disorder in terms of symptoms but rather in terms of conditions of occurrence, evolution and outcome thereof. This method produced two well-known results: the unification and recognition of <>, and the definition of <> (dementia praecox). These results are described in the Treatise of Psychiatry which has had eight editions during the author's lifetime (from 1883 to 1915), and which presents Kraepelin's systematic nosography covering the entire field of mental illness. Such an innovative method required special tools capable of exploring not only the symptoms, as had been done previously, but the pathological process per se: therefore, Kreapelin created a systematic method to conduct psychiatric research and founded a Research Establishment divided into different sections (histopathology, topographic histology, serology, genealogy). Alois Alzheimer and Franz Nissl, among others, were closely associated with his work. Kreapelin's thought was not set, however, and by the end of his career it took a turn toward a more comprehensive type of psychiatry (1920) taking into account the social aspects (<>). From the therapeutic and institutional viewpoints, Kraepelin remained faithful throughout his life to the no-restraint practice by abolishing any restraint methods wherever he worked; by establishing a trust-based relationship with the patients; by allowing the patients to correspond and by opening the institution to visitors. Additionally, he participated actively in the struggle against alcoholism and syphilis. He is also one of the initiators of cross-cultural psychiatry (<>). Although he lead a medical career, Kraepelin was also interested in experimental psychology, and he thought of his works in that area as more important than his clinical achievements. He was closely connected with Wilhelm Wundt with whom he worked (at the Institute of Psychology of Leipzig where Kraepelin was one of the first medical doctors to collaborate with Wundt) and then exchanged letters. Some of his experimental works, including the elaboration of series of tests aimed at studying the psychic effects of certain substances, herald the advent of psychopharmacology. Lastly, his Memoirs and Poems give insight on the intimate person of Kraepelin, as well as putting his affective life in perspective.

Characterization of p80, a novel nuclear and cytoplasmic protein in dinoflagellates.

The presence of myosin in dinoflagellates was tested using an anti-Acanthamoeba castellanii myosin II polyclonal antibody on the heterotrophic dinoflagellate Crypthecodinium cohnii Seligo. Western blots revealed the presence of a unique band of 80 kDa in total protein extracts and after immunoprecipitation. Expression of this 80 kDa protein appeared constant during the different phases of the cell cycle. In protein extracts from various other dinoflagellates, this 80 kDa protein was detected only in the autotrophic species Prorocentrum micans Ehr. Screening of a C. cohnii cDNA expression library with this antibody revealed a cDNA coding for an amino acid sequence without homology in the databases. However, particular regions were detected: - a polyglutamine repeat domain in the N-terminal part of the protein, - four peptide sequences associated with GTP-binding sites, - a sequence with slight homology to the rod tail of Caenorhabditis elegans myosin II, -a sequence with homology to a human kinesin motor domain. Immunocytolocalization performed on C. cohnii thin sections with a polyclonal antibody raised against the recombinant protein showed p80 to be present both within the nucleus and in the cytoplasm. Labelling was widespread in the nucleoplasm and more concentrated at the periphery of the permanently condensed chromosomes. In the cytoplasm, labelling appeared in a punctate region close to the nucleus and in the flagellum. Potential functions of this novel protein are discussed.

Cyclic expression of a nuclear protein in a dinoflagellate.

Nuclei of the dinoflagellate Crypthecodinium cohnii strain Whd were isolated and nuclear proteins were extracted in three fractions, corresponding to the increasing affinity of these proteins to genomic DNA. One fraction contained two major bands (48- and 46-kDa) and antibodies specific to this fraction revealed two major bands by Western blot on nuclear extracts, corresponding to the 46- and 48-kDa bands. The 48-kDa protein was detected in G1 phase but not in M phase cells. An expression cDNA library of C. cohnii was screened with these antibodies, and two different open reading frames were isolated. Dinoflagellate nuclear associated protein (Dinap1), one of these coding sequences, was produced in E. coli and appeared to correspond to the 48-kDa nuclear protein. No homologue of this sequence was found in the data bases, but two regions were identified, one including two putative zinc finger repeats, and one coding for two potential W/W domains. The second coding sequence showed a low similarity to non-specific sterol carrier proteins. Immunocytolocalization with specific polyclonal antibodies to recombinant Dinap1 showed that the nucleus was immunoreactive only during the G1 phase: the nucleoplasm was immunostained, while chromosome cores and nuclear envelopes were negative.

Dinoflagellate chromosome behaviour during stages of replication.

In most dinoflagellate species, chromosomes are characterized by an almost continuous condensation of the nucleofilaments throughout the cell cycle and the absence of longitudinal differentiation as Q, G, or C banding. Their supercoiled architecture is maintained by divalent cations and structural RNAs. Their chromatin is devoid of histones and nucleosomes and their DNA composition is distinctive: in several species, more than 60% of thymines are replaced by a rare base, hydroxymethyluracil. We report here an immunofluorescence (conventional and confocal laser scanning microscopy, CLSM) and immunogold transmission electron microscopy (TEM) analysis of some stages of the early replication process in Prorocentrum micans dinoflagellate cells, after long pulse incorporation (3, 6 or 9 days) with 50 micrograms/ml bromodeoxyuridine (BrdU) in the presence of 5-fluoro-2'-deoxyuridine (FUdR) and BrdU antibody technique (BAT) detection. The large DNA content (45 pg per nucleus) of P. micans cells is compacted on 100 chromosomes, 10 microns in length. In early S-phase, DNA replication sites are revealed as fluorescent domains organized in clusters, which appear in the periphery of the nucleus unlike other eukaryotes. In late S-phase, the number of labelled clusters increased; helically distributed, they did not appear synchronously in the whole chromosome. Under TEM, spherical domains of equivalent diameter appeared located all along the chromosomes after 6 days BrdU pulse. Replication occurs, but in our experimental conditions, segregation of daughter chromosomes was never observed. The blockade of the cell cycle after BrdU incorporation intervening just before the segregation of daughter chromosomes is discussed.

Colocalization of the cyclin B homologue p56 and beta-tubulin during the cell cycle in a unicellular eucaryote dinoflagellate.

We provide evidence for an unusual behavior of the cyclin B homologue, p56, in the dinoflagellate Crypthecodinium cohnii. p56, of which we previously demonstrated the presence in this original eukaryotic protist, is present all along the cell cycle progression, and is exclusively cytoplasmic as revealed after immunofluorescence labeling with anti-p56 Ab and counterstaining with Dapi. It was never found in the nucleus as is the case in higher eukaryotic cells. During mitosis, p56 was essentially associated with the mitotic apparatus: centrosomes and mitotic spindle, as shown after double immunofluorescence labeling with anti p56 and anti beta-tubulin Ab. Using high pressure freeze fixation, we clearly detected in transmission electron microscopy (TEM) the localization of p56 cyclin B homologue and beta-tubulin: single immunogold labeling demonstrated that p56 is localized along the whole cell cortex, along the cleavage furrow of anaphase to cytokinesis cells and into cytoplasmic channels passing throughout the mitotic nucleus where is located the mitotic spindle. Double immunogold labeling realized with anti-p56 and anti-beta-tubulin antibodies confirm that p56 antigens colocalize with beta-tubulin in many sites. The significance of the exclusively cytoplasmic localization of the cyclin B homologue is discussed.

Cloning, characterization and chromosomal localization of a repeated sequence in Crypthecodinium cohnii, a marine dinoflagellate.

Genomic DNA of Crypthecodinium cohnii has been extracted in the presence of cetylmethylammonium bromide and hydrolysed by 13 restriction enzymes. No typical ladder-like pattern or isolated band of satellite sequences were found with any of these enzymes. A "mini" genomic DNA library had been made and screened by reverse hybridization to isolate highly repeated sequences. Seven such DNA fragments were sequenced. The copy number of one of them (Cc18), 226 bp long, was estimated at around 25,000, representing 0.06% of the total genome. Cc18 was found to be included in a higher fragment of 3.0 kb by Southern blot analysis after cleavage by PstI. This higher molecular weight fragment could be composed either of tandemly repeated Cc18 sequences, or by only one or a very low copy number of Cc18. In this latter case, these fragments, also repeated 25,000 times would represent 1 to 2% of the total genome. Genomic localization of Cc18 by in situ hybridization on squashed C. cohnii cells showed that it was widely distributed on the different chromosomes. All the chromosomes observed displayed Cc18 labeling, which appeared homogeneously distributed. The ability of Cc18 to be a specific molecular marker to distinguish sibling C. cohnii species is discussed.

[Emil Kraepelin and bipolar disorder: invention or over-extension?]. / Emil Kraepelin et la bipolarité: invention ou dépassement?

From 1899 to 1913, Emil Kraepelin (1856-1926) creates and elaborates the nosographical group of the "manic-depressive insanity". In the 50-60s, Leonhard splits off this homogeneous group and describes unipolar psychosis, bipolar psychosis and cycloïd psychosis (anxiety-elation psychosis, motility psychosis and confusion psychosis). Recent nosographical orientations seem to announce a come-back to Kraepelin's conception of "mood disorders". This paper presents the essential of Kraepelin's "manic-depressive insanity" theory-temperamental basis, integration of mixed states, epidemiological datas- and highlights its dialectical relations with today's theory of bipolarity.

Cyclin B (p56cdc13) localization in the yeast Schizosaccharomyces pombe: an ultrastructural and immunocytochemical study.

The eucaryote cell cycle is driven by a set of cyclin dependent kinases (CDKs) associated to cyclins, which confer not only the activity but also the substrate specificity and the proper localization of the kinase activity. In the fission yeast Schizosaccharomyces pombe, only one cyclin, the product of the cdc13 gene (p56cdc13), is required to be associated with p34cdc2, to control the complete cell cycle. Earlier studies have localized this complex mainly in the nucleus and its periphery. Using new improved electron microscopy (EM) technologies, based on high pressure freezing fixation, we refined previous studies, evidencing cytoplasmic localization of p56cdc13, in addition to the nuclear localization previously observed. Further immunofluorescence studies, performed on aldehydically fixed cells, confirmed our EM results, emphasizing the major cytoplasmic localization of p56cdc13 in interphase cells and the relocalization towards the nucleus in mitotic cells, suggesting that the S pombe cyclin B localization is cell cycle-regulated.

Nuclear and cytoplasmic actin in dinoflagellates.

Experiments using monoclonal and polyclonal anti-actin antibodies allowed us to demonstrate the presence of F- or G-actin in original protists, dinoflagellates, either by biochemistry, immunofluorescence and in TEM. SDS-PAGE electrophoresis and immunoblottings made either from total or nuclear protein extracts revealed the presence of a 44-kDa band reacting with monoclonal anti-actin antibody in two species, Prorocentrum micans and Crypthecodinium cohnii, and thus demonstrated the presence of actin in nuclear and cytoplasmic fractions. After squash preparation of P micans cells, actin was identified within the nucleus and in some regions of the cytoplasm by immunofluorescence microscopy. Labelling of both the nucleolus and the centrosome region was evident together with amorphous nucleoplasmic material surrounding the chromosomes. The use of cryosections of intact P micans and C cohnii cells for immunofluorescence along with staining with DAPI to delineate the chromosomes themselves, yielded finer resolution of the intranuclear network labelling pattern and allowed us to complete our observations, in particular on the cytoplasmic labelling. In P micans, in addition to the centrosome region, the cytoplasmic channels passing through the nucleus in dividing cells are labelled. In C cohnii, the cortex, the centrosome region, the cytoplasmic channels, the region surrounding the nucleus, the filaments linking it to the cortex and the cleavage furrow are also labelled. In the nucleus of the two species, there is a prominent "weft' of fine actin filaments in the nucleoplasm forming a matrix of varying density around the persistent chromosomes. This actin matrix, of unknown function, is most conspicuous at the end of the S-phase of the cell cycle. Fluorescent derivatives of phalloidin, used as diagnostic cytochemical probes for polymeric actin (F-actin), gave similar results. Positive TEM immunolabelling of intranuclear actin confirms its presence in the nucleoplasm, in the nucleolus where the preribosomal region is labelled while C cohnii chromosomes are unlabelled and the P micans chromosomes very slightly. In the cytoplasm, lips of the cleavage furrow and kinetosome regions are labelled as well as the centrosome region. The possible functions of this protein located in several compartments of dinoflagellate cells are discussed.

Identification of an HSP70-related protein associated with the centrosome from dinoflagellates to human cells.

The monoclonal antibody CTR210 raised against isolated human centrosomes strongly decorates the centrosome and more weakly a domain congruent with the Golgi apparatus in several animal cells (HeLa, 3T3, CHO, PtK2). Both decorations resist Triton extraction in conditions which totally extract the Golgi apparatus, as judged by galactosyltransferase decoration. A 67 kDa centrosomal antigen can be demonstrated in human cells with this antibody. CTR210 also decorates the centrosome or associated structures in several systems, including unicellular eukaryotes such as dinoflagellates or ciliates. A 72 kDa antigen has been identified and purified from the dinoflagellate C. cohnii and its NH2-terminal sequence partially established. It shows a close homology with HSP70 proteins. The possibility that the 72 kDa antigen belongs to this chaperone family was further supported using a mAb reacting, in most species, with HSP70. A polyclonal antibody raised against the 72 kDa antigen from C. cohnii decorates the centrosome in human cells and reacts with the CTR210 centrosomal 67 kDa antigen. These results suggest that specific chaperone proteins are associated with the centrosome in eukaryotic cells. The centrosomal chaperones could participate in the microtubule nucleation reaction or in the process of centrosome assembly.

[Morbidity of radical prostatectomy for localized cancer of the prostate. Apropos of 100 cases]. / Morbidité de la prostatectomie radicale pour cancer localisé de la prostate. A propos de 100 cas.

Adenocarcinoma of the prostate is the most frequent cancer of male over 60 years of age. Radical prostatectomy is one of the preferred modes of treatment for localized stages. Surgical morbidity decreases with experience and consists mainly in bleeding and rectal injury. Delayed morbidity comprises loss of erection, anastomosis stricture, incontinence. A retrospective study of 100 patients is reported.