Curt F. Bühler discusses the impact of the epoch-making invention on the scribes as well as the attitudes that the contemporary book-lovers adopted toward the products of the press.
The ergot alkaloids, a class of fungal‐derived natural products with important biological activities, are derived from a common intermediate, chanoclavine‐I, which is elaborated into a set of diverse ...structures. Herein we report the discovery of the biosynthetic pathway of cycloclavine, a complex ergot alkaloid containing a cyclopropyl moiety. We used a yeast‐based expression platform along with in vitro biochemical experiments to identify the enzyme that catalyzes a rearrangement of the chanoclavine‐I intermediate to form a cyclopropyl moiety. The resulting compound, cycloclavine, was produced in yeast at titers of >500 mg L−1, thus demonstrating the feasibility of the heterologous expression of these complex alkaloids.
Who's responsible for the ring? The biosynthetic pathway of the ergot alkaloid cycloclavine (see scheme) was discovered and reconstituted in yeast at titers of >500 mg L−1. A yeast‐based expression platform and in vitro biochemical experiments enabled the identification of the enzyme that catalyzes the unprecedented rearrangement of a biosynthetic intermediate to form the cyclopropyl moiety of cycloclavine.
Abstract Objectives In a clinical population, we estimated the frequency of mood disorders among 271 patients suffering from Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in comparison to a control ...group matched for age and gender. Method The frequency of mood disorders was measured using the Mini International Neuropsychiatric Interview (MINI), DSM-IV version. Results Mood disorders were more frequent among eating disorder (ED) patients than among controls, with a global prevalence of the order of 80% for each ED group. The majority of the mood disorders comorbid with ED were depressive disorders (MDD and dysthymia). The relative chronology of onset of these disorders was equivocal, because mood disorders in some cases preceded and in others followed the onset of the eating disorders. Limitations Our sample was characterized by patients with severe ED and high comorbidities, and thus do not represent the entire population of AN or BN. This also may have resulted in an overestimation of prevalence. Conclusion Mood disorders appear significantly more frequently in patients seeking care for ED than in controls. These results have implications for the assessment and treatment of ED patients, and for the aetio-pathogenesis of these disorders.
Depression and anxiety are commonly associated with anorexia nervosa (AN) and contribute to difficulties in social integration, a negative factor for outcome in AN. The link between those disorders ...and AN has been poorly studied. Thus, our objective was to investigate (1) the link between outcome nine years after hospitalisation for AN and the occurrence of lifetime anxious or depressive comorbidities; (2) the prognostic value of these comorbidities on patient outcome; 181 female patients were hospitalised for AN (between 13 and 22 years old), and were re-evaluated for their psychological, dietary, physical and social outcomes, from 6 to 12 years after their hospitalisation. The link between anxious and depressive disorders (premorbid to AN and lifetime) and the outcome assessment criteria were tested through multivariate analyses; 63% of the participants had good or intermediate outcome, 83% had presented at least one anxiety or depression disorder in the course of their lives, half of them before the onset of AN. Premorbid obsessive compulsive disorders (OCD), BMI at admission, and premenarchal AN all contribute to poor prognosis. Social phobia and agoraphobia affect the subjects’ quality of life and increase eating disorder symptoms. These results encourage a systematic assessment of, and care for, anxiety and depression comorbidities among female adolescent patients with a particular focus on premorbid OCD.
Anorexia nervosa is often accompanied by comorbid mood disorders, in particular depression, but individual or family history of bipolar disorders has not frequently been explored in anorexia nervosa. ...The objectives of the present study were: (1) to assess the frequency of bipolar disorders in patients with anorexia nervosa hospitalized in adolescence and in their parents, (2) to determine whether the patients with a personal or family history of bipolar disorders present particular characteristics in the way in which anorexia nervosa manifests itself, in their medical history, in the secondary diagnoses established, and in the treatments prescribed.
Overall, 97 female patients aged 13 to 20 hospitalized for anorexia nervosa and their parents were assessed. The diagnoses of anorexia nervosa and bipolar disorders were established on the basis of DSM-IV-TR criteria.
A high frequency of type II and type V bipolar disorders was observed. The patients with anorexia nervosa and presenting personal or family histories of bipolar disorder had an earlier onset of anorexia nervosa, more numerous hospitalizations, a longer time-lapse between anorexia nervosa onset and hospitalization, more suicide attempts and more psychiatric comorbidities.
The occurrence of anorexia nervosa-bipolar disorders comorbidity appears to be considerable and linked to the severity of anorexia nervosa, raising the issue of the relationship between anorexia nervosa and bipolar disorders.
ABSTRACT
Objectives:
Recent advances in medical and surgical management have led to improved long‐term survival in children with intestinal failure. Yet, limited data exist on their ...neurodevelopmental and cognitive outcomes. The aim of the present study was to measure neurodevelopmental outcomes in children with intestinal failure.
Methods:
Children enrolled in a regional intestinal failure program underwent prospective neurodevelopmental and psychometric evaluation using a validated scoring tool. Cognitive impairment was defined as a mental developmental index <70. Neurodevelopmental impairment was defined as cerebral palsy, visual or hearing impairment, or cognitive impairment. Univariate analyses were performed using the Wilcoxon rank‐sum test. Data are presented as median (range).
Results:
Fifteen children with a remnant bowel length of 18 (5–85) cm were studied at age 17 (12–67) months. Thirteen patients remained dependent on parenteral nutrition. Twelve (80%) subjects scored within the normal range on cognitive testing. Each child with cognitive impairment was noted to have additional risk factors independent of intestinal failure including cardiac arrest and extreme prematurity. On univariate analysis, cognitive impairment was associated with longer inpatient hospital stays, increased number of surgical procedures, and prematurity (P < 0.02). In total, 4 (27%) children demonstrated findings consistent with neurodevelopmental impairment.
Conclusions:
A majority of children with intestinal failure demonstrated normal neurodevelopmental and cognitive outcomes on psychometric testing. These data suggest that children with intestinal failure without significant comorbidity may be at low risk for long‐term neurodevelopmental impairment.
Ergot alkaloids are a group of highly bioactive molecules produced by a number of filamentous fungi. These compounds have been intensely studied for decades, mainly due to their deleterious effects ...in contaminated food and feeds, but also for their beneficial pharmaceutical and agricultural applications. Biosynthesis of ergot alkaloids goes via the common intermediate chanoclavine-I, and studies of the key enzymes, EasE and EasC, involved in chanoclavine-I formation, have relied on gene complementation in fungi, whereas further characterization has been hampered by difficulties of poor EasE protein expression. In order to facilitate the study of ergot alkaloids, and eventually move towards commercial production, the early steps of the biosynthetic pathway were reconstituted in the unicellular yeast Saccharomyces cerevisiae.
The genomic sequence from an ergot alkaloid producer, Aspergillus japonicus, was used to predict the protein encoding sequences of the early ergot alkaloid pathway genes. These were cloned and expressed in yeast, resulting in de novo production of the common intermediate chanoclavine-I. This allowed further characterization of EasE and EasC, and we were able to demonstrate how the N-terminal ER targeting signal of EasE is crucial for activity in yeast. A putative, peroxisomal targeting signal found in EasC was shown to be nonessential. Overexpression of host genes pdi1 or ero1, associated with disulphide bond formation and the ER protein folding machinery, was shown to increase chanoclavine-I production in yeast. This was also the case when overexpressing host fad1, known to be involved in co-factor generation.
A thorough understanding of the enzymatic steps involved in ergot alkaloid formation is essential for commercial production and exploitation of this potent compound class. We show here that EasE and EasC are both necessary and sufficient for the production of chanoclavine-I in yeast, and we provide important new information about the involvement of ER and protein folding for proper functional expression of EasE. Moreover, by reconstructing the chanoclavine-I biosynthetic pathway in yeast we demonstrate the advantage and potential of this host, not only as a convenient model system, but also as an alternative cell factory for ergot alkaloid production.
Patients with severe Anorexia Nervosa (AN) whose condition is life-threatening or who are not receiving adequate ambulatory care are hospitalized. However, 40 % of these patients leave the hospital ...prematurely, without reaching the target weight set in the treatment plan, and this can compromise outcome. This study set out to explore factors predictive of dropout from hospital treatment among patients with AN, in the hope of identifying relevant therapeutic targets.
From 2009 to 2011, 180 women hospitalized for AN (DSM-IV diagnosis) in 10 centres across France were divided into two groups: those under 18 years (when the decision to discharge belongs to the parents) and those aged 18 years and over (when the patient can legally decide to leave the hospital). Both groups underwent clinical assessment using the Morgan & Russell Global Outcome State questionnaire and the Eating Disorders Examination Questionnaire (EDE-Q) for assessment of eating disorder symptoms and outcome. Psychological aspects were assessed via the evaluation of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). Socio-demographic data were also collected. A number of factors identified in previous research as predictive of dropout from hospital treatment were tested using stepwise descending Cox regressions.
We found that factors predictive of dropout varied according to age groups (being under 18 as opposed to 18 and over). For participants under 18, predictive factors were living in a single-parent family, severe intake restriction as measured on the "dietary restriction" subscale of the Morgan & Russell scale, and a low patient-reported score on the EDE-Q "restraint concerns" subscale. For those over 18, dropout was predicted from a low depression score on the HADS, low level of concern about weight on the EDE-Q subscale, and lower educational status.
To prevent dropout from hospitalization for AN, the appropriate therapeutic measures vary according to whether patients are under or over 18 years of age. Besides the therapeutic adjustments required in view of the factors identified, the high dropout rate raises the issue of resorting more frequently to compulsory care measures among adults.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction La non-adhésion diminue largement l’efficacité des antidépresseurs 1,2 , dont la représentation évolue dans un contexte particulièrement défiant et médiatiquement tendu. Objectif ...L’objectif de cette étude est de : – évaluer l’adhésion aux antidépresseurs chez des patients hospitalisés pour épisode dépressif majeur ; – explorer les représentations que les patients ont des antidépresseurs et de la dépression, ainsi que la perception de la stigmatisation aux troubles mentaux ; – analyser la relation entre les attitudes face aux antidépresseurs et des paramètres sociodémographiques et cliniques. Méthode L’adhérence était évaluée chez 40 patients en utilisant la version courte du Drug Attitude Inventory (DAI-10), complétée par un questionnaire mesurant les connaissances, craintes, impact des média et stigmatisation liés aux antidépresseurs. Des entretiens d’investigation étaient ensuite menés à l’aide de celui-ci. Résultats L’âge moyen de l’échantillon est de 43 ans, dont 27 % d’homme. Il s’agit d’un premier épisode pour 40 % des patients. La médiane du DAI est de 3,5 (échelle de −10 à +10), et 30 % des patients ne sont pas adhérents. Les hommes de l’échantillon ont une plus mauvaise représentation des antidépresseurs (−2 VS 4 ; U de Mann-Whitney = 90,50 ; p = 0,0035). Soixante-dix pour cent des patients ont des craintes par rapport à leur antidépresseur (prise de poids et dépendance au premier rang). Vingt pour cent des patients n’ont pas dit à leur entourage qu’ils prenaient des médicaments contre la dépression. Discussion Une intervention à de multiples niveaux pourrait augmenter les connaissances des patients ainsi que de l’opinion publique 3 . Une collaboration spécifique entre journalistes et psychiatres permettrait une meilleure connaissance et une diffusion plus représentative des enjeux de santé mentale dans les média 4 . Des actions de santé publique et initiatives citoyennes pourraient aussi être profitables aux patients. Conclusion L’adhérence aux antidépresseurs peut largement être améliorée, la stigmatisation restant une barrière aux traitements et à la prise en charge.
Slavic Dialectology Greenberg, Marc L.; Borowski, Krzysztof E.; Schallert, Joseph ...
Journal of Slavic linguistics,
06/2017, Letnik:
25, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The last 25 years in Slavic dialectology mark the period not only of JSL's founding but also of major and multiple political, social, and economic reorganizations in predominantly Slavic-speaking ...states. During this period research institutions and their priorities and projects have both continued and changed; technological innovation has meant moving towards electronic dissemination, "digital humanities," and innovative modes of presenting research data and findings. In some cases major works (e.g., dialect atlases) have advanced during this period. Moreover, a new generation of scholars has had greater opportunities for mobility and therefore exposure to a variety of linguistic frameworks and approaches, which has fostered cross-border collaboration in the field. The present essay gives an overview of progress made on dialect projects both created institutionally and individually and including both traditional (book, article) and new digital means of dissemination.
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