RESUMEN
CONTEXT: In France, care workers and health students have been intensely mobilized during the first wave of the COVID-19 pandemic. But few studies have evaluated psychological distress on non-medical health students, in addition to the challenges posed by pedagogical continuity while universities are closed following health and safety regulations. OBJECTIVES: This study aims to assess COVID-19's impact on health students in France on different levels: psychological, educational and social. METHODS: An online national cross-sectional study, from April 11 to May 30 2020, included sociodemographic, work conditions and numeric scales. RESULTS: A total of 4411 students answered. Regarding the K6 scale, 39% of students had moderate distress, and 21% had a high level of distress. Risk factors of psychological distress included being a woman (P<0.001), being between 19 and 21 years old (P<0.001), living alone (P=0.008), and not having the ability to isolate (P<0.001). Students on the frontline had less psychological distress (57 vs 62%, P=0.003), better quality of sleep (34% vs 28% high quality, P<0.001) but a higher consumption of medical (8.5% vs 6.5%, P=0.044) and non-medical (18% vs 10%, P<0.001) psychotropic drugs. Nurse and medical students had more distress and used more non-medical psychotropic substances than other health students (15% vs 9.2%). DISCUSSION: COVID-19' crisis had an important impact on health students' mental health, social life and training with discrepancies regarding the speciality whether they were on the frontline or not. There is an urgent need for psychological and pedagogical support for students, and even more so regarding the prolongation of the COVID-19 epidemic.
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COVID-19 , Estudiantes de Medicina , Femenino , Humanos , Adulto Joven , Adulto , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Estudios Transversales , Estudiantes de Medicina/psicologíaRESUMEN
BACKGROUND: Residual depressive symptoms are generally documented as a risk factor for recurrence. In the absence of a specific instrument for the assessment of residual symptoms, a new 25-item Depression Residual Symptom Scale (DRSS) was elaborated and tested for recurrence prediction over a 1-year follow-up. SAMPLING AND METHODS: Fifty-nine patients in remission after a major depressive episode (MDE) were recruited in two centres. They were assessed with the DRSS and the Montgomery-Asberg Depression Rating Scale (MADRS) at inclusion and followed for 1 year according to a seminaturalistic design. The DRSS included specific depressive symptoms and subjective symptoms of vulnerability, lack of return to usual self and premorbid level of functioning. RESULTS: Severity of residual symptoms was not significantly associated with increased risk of recurrence. However, DRSS score was significantly higher among patients with three or more episodes than one to two episodes. Number of previous episodes and treatment interruption were not identified as significant predictors of recurrence. CONCLUSION: The proposed instrument is not predictive of depressive recurrence, but is sensitive to increased perception of vulnerability associated with consecutive episodes. Limitations include small sample size, seminaturalistic design (no standardisation of treatment) and content of the instrument.
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Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Encuestas y Cuestionarios , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Factores de Tiempo , Adulto JovenRESUMEN
We investigated plasma cortisol in a psychological stress paradigm in seven weaned anhedonic alcoholics in comparison with seven age-matched healthy controls. Alcoholics had significantly higher mean plasma cortisol at baseline and no increase following a psychological stress paradigm. Anhedonic alcoholics judged the experimental situation less agreeable than controls. Anhedonic alcoholics may have blunted cortisol response to psychological stress.
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Síntomas Afectivos/sangre , Síntomas Afectivos/psicología , Alcoholismo/sangre , Alcoholismo/psicología , Nivel de Alerta/fisiología , Hidrocortisona/sangre , Estrés Psicológico/complicaciones , Adulto , Alcoholismo/rehabilitación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distorsión de la Percepción/fisiología , Solución de Problemas/fisiología , Percepción del Habla/fisiología , Estrés Psicológico/sangre , Templanza/psicología , Conducta Verbal/fisiologíaAsunto(s)
Comorbilidad , Unidades Hospitalarias/organización & administración , Medicina Interna/organización & administración , Trastornos Mentales/complicaciones , Psiquiatría/organización & administración , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Trastorno Depresivo/complicaciones , Femenino , Francia/epidemiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Persona de Mediana Edad , Evaluación de Necesidades , Sarcoidosis/complicacionesRESUMEN
Salicylates are effective prophylactic treatment strategies for myocardial infarction and ischemic strokes. Recent evidence suggests that high doses of salicylates may exert direct, platelet-independent effects on the vascular wall. Salicylate and aspirin, in concentrations between 1 and 5 mM, effectively inhibit vascular smooth muscle cell proliferation and DNA synthesis without inducing cellular toxicity or apoptosis. This inhibition is associated with effects on specific cell-cycle regulatory molecules, and may proceed via downregulation of the transcription factor, nuclear factor (NF)-kappaB. High-dose salicylates and selective NF-kappaB inhibitors may, therefore, play an important role in the management of vascular proliferative disorders.
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Ciclo Celular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Salicilatos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , División Celular/efectos de los fármacos , Regulación hacia Abajo , Humanos , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , FN-kappa B/efectos de los fármacos , FN-kappa B/fisiologíaRESUMEN
BACKGROUND: Salicylates may have direct vascular effects by mechanisms that are independent of platelet inhibition. METHODS AND RESULTS: We investigated the effect of salicylates on vascular smooth muscle cell (SMC) proliferation in response to platelet-derived growth factor (PDGF) in vitro. Salicylate concentrations of 5 and 10 mmol/L inhibited serum- or PDGF-induced SMC cell count and [(3)H]thymidine incorporation by 62% and 81%, respectively. There was no evidence of cellular toxicity or apoptosis as determined by trypan blue exclusion and FACS analyses. Because cell cycle progression is regulated by hyperphosphorylation of the retinoblastoma (Rb) protein, we examined the effects of salicylate on Rb hyperphosphorylation. Treatment with salicylate, but not indomethacin, inhibited nuclear factor-kappaB activation and completely abolished Rb hyperphosphorylation in PDGF-treated SMCs. This effect was associated with a decrease in cyclin-dependent kinase (Cdk)-2 and, to a lesser extent, Cdk-6, but not Cdk-4 activity, without changes in Cdk-2, -4, and -6 and cyclin D and E protein levels. Because Cdk-2 activity is regulated by the Cdk inhibitors p21(Waf1) and p27(Kip1), we studied the effects of salicylate on p21(Waf1) and p27(Kip1) expression. Treatment with salicylate prevented PDGF-induced downregulation of p21(Waf1) and p27(Kip1) but not of the Cdk-4/-6 inhibitor p16(Ink4). CONCLUSIONS: These findings indicate that high doses of salicylates inhibit SMC proliferation by cell cycle arrest at the G(1)-S phase and suggest a beneficial role for high-dose salicylates in the treatment of vascular proliferative disorders.
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Proteínas de Ciclo Celular , Ciclinas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Salicilato de Sodio/farmacología , Proteínas Supresoras de Tumor , Antiinflamatorios no Esteroideos/farmacología , Apoptosis , Aspirina/farmacología , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , ADN/biosíntesis , ADN/efectos de los fármacos , Inhibidores Enzimáticos/metabolismo , Humanos , Indometacina/farmacología , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , FN-kappa B/metabolismo , Fosforilación , Proteína de Retinoblastoma/metabolismo , Regulación hacia ArribaRESUMEN
Excision and formation of a covalently closed circular transposon molecule are required for conjugative transposition of Tn916 but are not the only factors that limit the frequency of conjugative transposition from one host to another. We found that in gram-positive bacteria, an increase in the frequency of excision and circularization of Tn916 caused by expression of integrase (Int) and excisionase (Xis) from a xylose-inducible promoter does not lead to an increase in the frequency of conjugative transposition. We also found that the concentration of Int and Xis in the recipient cell does not limit the frequency of conjugative transposition and that increased excision does not result in increased expression of transfer functions required to mobilize a plasmid containing the Tn916 origin of transfer. We conclude that in gram-positive hosts in which the Tn916 functions Int and Xis are overexpressed, the frequency of conjugative transposition is limited by the availability of transfer functions.
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Bacillus subtilis/genética , Conjugación Genética , Elementos Transponibles de ADN , Enterococcus faecalis/genética , Proteínas Virales , ADN Nucleotidiltransferasas/biosíntesis , ADN Circular , ADN Superhelicoidal , Integrasas/biosíntesis , Mutagénesis Insercional , PlásmidosRESUMEN
The mechanism by which platelet-derived growth factor (PDGF) regulates vascular smooth muscle cell (SMC) DNA synthesis is unknown, but may involve isoprenoid intermediates of the cholesterol biosynthetic pathway. Inhibition of isoprenoid synthesis with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, simvastatin (Sim, 1-10 microM), inhibited PDGF-induced SMC DNA synthesis by >95%, retinoblastoma gene product hyperphosphorylation by 90%, and cyclin-dependent kinases (cdk)-2, -4, and -6 activity by 80 +/- 5, 50 +/- 3, and 48 +/- 3%, respectively. This correlated with a 20-fold increase in p27(Kip1) without changes in p16, p21(Waf1), or p53 levels compared with PDGF alone. Since Ras and Rho require isoprenoid modification for membrane localization and are implicated in cell cycle regulation, we investigated the effects of Sim on Ras and Rho. Up-regulation of p27(Kip1) and inhibition of Rho but not Ras membrane translocation by Sim were reversed by geranylgeranylpyrophosphate, but not farnesylpyrophosphate. Indeed, inhibition of Rho by Clostridium botulinum C3 transferase or overexpression of dominant-negative N19RhoA mutant increased p27(Kip1) and inhibited retinoblastoma hyperphosphorylation. In contrast, activation of Rho by Escherichia coli cytotoxic necrotizing factor-1 decreased p27(Kip1) and increased SMC DNA synthesis. These findings indicate that the down-regulation of p27(Kip1) by Rho GTPase mediates PDGF-induced SMC DNA synthesis and suggest a novel direct effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors on the vascular wall.
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Proteínas de Ciclo Celular , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Proteínas Asociadas a Microtúbulos/genética , Músculo Liso Vascular/efectos de los fármacos , Proteínas/metabolismo , Simvastatina/farmacología , Proteínas Supresoras de Tumor , Aorta , Células Cultivadas , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Inhibidores Enzimáticos/metabolismo , GTP Fosfohidrolasas/metabolismo , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Proteínas Activadoras de GTPasa , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Cinética , Ácido Mevalónico/farmacología , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Factor de Crecimiento Derivado de Plaquetas/farmacología , Proteínas/antagonistas & inhibidores , Vena Safena , Túnica Media/citología , Túnica Media/efectos de los fármacos , Túnica Media/metabolismo , Proteínas Activadoras de ras GTPasa , Proteína de Unión al GTP rhoARESUMEN
In Lactococcus lactis excision of Tn916 is limited by the concentration of integrase and is increased by providing more excisionase. However, even with increased excision of Tn916 in L. lactis, no conjugative transfer is detectable. This suggests that L. lactis is deficient in a host factor(s) required for conjugative transposition.
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Conjugación Genética , Elementos Transponibles de ADN , Lactococcus lactis/genética , Proteínas Virales , ADN Nucleotidiltransferasas/genética , ADN Nucleotidiltransferasas/metabolismo , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Expresión Génica , Integrasas/genética , Integrasas/metabolismo , Lactococcus lactis/metabolismoRESUMEN
Excision from the donor DNA molecule is the first step in conjugative transposition of Tn916 and is followed by circularization of the transposon and its transfer to a new host. We have demonstrated that, in Gram-positive hosts, the Xis protein, as well as the site-specific recombinase Int, is required for the excision of Tn916. Using assays for closure of the excised covalently closed transposon and for repair of the donor DNA molecule, we found that neither protein alone is rate limiting for excision, but overexpression of Int and Xis together results in increased excision. After excision, the frequency of Tn916 circle formation was found to be the same as the frequency of repair of the donor DNA molecule. This suggests that a single reaction results in the closure of both molecules. We have also identified two transcripts that encode Int, one of which also encodes Xis and one of which does not, suggesting that there are steps in conjugative transposition of Tn916 that require Int without Xis.
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Conjugación Genética , ADN Nucleotidiltransferasas/genética , Regulación Bacteriana de la Expresión Génica , Integrasas , Transposasas , Proteínas Virales , Bacillus subtilis , Secuencia de Bases , Sitios de Unión , Reparación del ADN , ADN Circular , Escherichia coli , Datos de Secuencia Molecular , Mutagénesis , Sistemas de Lectura Abierta , Regiones Promotoras Genéticas , RecombinasasRESUMEN
The aim of this study was to determine the role of anhedonia among other psychopathological dimensions in the relapse of alcoholics 6 months after withdrawal. Psychometric assessments included: the Social and Physical Anhedonia Scales, the Sensation Seeking Scale, the Pleasure-Displeasure Scale (including Fawcett-Clark's Pleasure Scale), the Depressive Mood Scale, the Thymasthenic Syndrome Rating Scale and the Comprehensive Psychopathological Rating Scale. Forty-four alcoholics participated in the study. The baseline values recorded during the second week of treatment showed that the more anhedonic the alcoholics were, the less they sought sensations. Type 2 alcoholics (Cloninger's classification) scored higher on the Thrill and Adventure Seeking Subscale. Relapsed alcoholics had higher baseline values on the Thrill and Adventure Seeking Subscale. This was in agreement with the step-wise discriminant analysis which showed that this subscale was the main variable that differentiated abstinent alcoholics from those who relapsed. Our results indicate that anhedonia does not predict relapse.
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Alcoholismo/psicología , Adulto , Alcoholismo/etiología , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , RecurrenciaRESUMEN
We characterized the regulated activity of the lactococcal nisA promoter in strains of the gram-positive species Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis, and Bacillus subtilis. nisA promoter activity was dependent on the proteins NisR and NisK, which constitute a two-component signal transduction system that responds to the extracellular inducer nisin. The nisin sensitivity and inducer concentration required for maximal induction varied among the strains. Significant induction of the nisA promoter (10- to 60-fold induction) was obtained in all of the species studied at a nisin concentration just below the concentration at which growth is inhibited. The efficiency of the nisA promoter was compared to the efficiencies of the Spac, xylA, and lacA promoters in B. subtilis and in S. pyogenes. Because nisA promoter-driven expression is regulated in many gram-positive bacteria, we expect it to be useful for genetic studies, especially studies with pathogenic streptococci in which no other regulated promoters have been described.
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Bacillus subtilis/genética , Regulación Bacteriana de la Expresión Génica , Lactococcus lactis/genética , Regiones Promotoras Genéticas , Streptococcaceae/genética , Factores de Transcripción , Bacillus subtilis/efectos de los fármacos , Proteínas Bacterianas/fisiología , Secuencia de Bases , Relación Dosis-Respuesta a Droga , Glucuronidasa/metabolismo , Pruebas de Sensibilidad Microbiana , Nisina/genética , Nisina/metabolismo , Nisina/farmacología , Plásmidos/genética , Transducción de Señal , Streptococcaceae/efectos de los fármacosRESUMEN
In this paper, the current status of the Molecular Probe Data Base (http://www.biotech.ist.unige.it/interlab/ mpdb.html ) is briefly presented together with a short analysis of its activity during 1997. This has been performed by statistically evaluating the 'logs' of the Internet servers that are used for its distribution with reference to the geographical origin of the requests, the words that were utilized to carry out of the searches and the oligonucleotides that were retrieved. Planned enhancements of this database are also described. They include a revision of its data structure and, even more relevant, of its data management procedures.
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Bases de Datos Factuales , Sondas Moleculares/genética , Redes de Comunicación de Computadores , Almacenamiento y Recuperación de la InformaciónRESUMEN
Different methods have been developed in clinical abuse liability testing in man. Tolerance, psychic and/or physical dependence must be investigated through clinical studies during drug development of a new substance. Adequate methodology is needed using double-blind, time-blind evaluations, comparisons of different dose levels and duration of treatment for a given drug, abrupt and gradual interruption of treatment, appropriate period of observation after treatment cessation ... The optimal scale to evaluate properly the symptoms occurring after drug discontinuation is still under investigation. These studies will or should permit the differentiation of rebound, withdrawal and recurrence. Methods developed to study reinforcing effects in post-addicts and healthy subjects are self-administration and choice procedures. In addition, the more traditional approach has been through assessing self-reported effects in which standardized questionnaires are used (Addiction Research Center Inventory or A.R.C.I.; Single Dose Questionnaire or S.D.Q.). A third focus of measurement has been discrimination studies performed in individuals with histories of drug abuse as well as healthy subjects. Abuse-liability testing of a new compound needs a multidimensional assessment to optimize the predictivity in defining the relative risk.
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Trastornos Relacionados con Sustancias/prevención & control , Conducta Adictiva , Ensayos Clínicos como Asunto , Humanos , Factores de Riesgo , Autoadministración , Síndrome de Abstinencia a Sustancias/diagnóstico , Encuestas y CuestionariosRESUMEN
Transposition of conjugative transposons proceeds by excision and formation of a covalently closed circular intermediate that includes at its joint the six flanking bases from its previous host (coupling sequences). To elucidate the role of the coupling sequences in this process and to determine the sequence of targets used by Tn916, we studied its insertion into a plasmid following conjugation. The results differ from those previously observed when Tn916 was introduced by transformation. They suggest that only one specific strand of the transposon molecule is transferred during the conjugation event and that complementary strand synthesis produces a double-stranded transposon circle with no mismatches which serves as the reaction intermediate. Tn916 inserts preferentially at specific sites and the same targets are used when Tn916 comes from donors with different coupling sequences. An analysis of the sequences of preferred targets is presented.
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Conjugación Genética , Elementos Transponibles de ADN/genética , Bacterias Grampositivas/genética , Recombinación Genética , Bacillus subtilis/genética , Secuencia de Bases , Cloranfenicol O-Acetiltransferasa/genética , Resistencia al Cloranfenicol/genética , Cruzamientos Genéticos , ADN Bacteriano/genética , ADN Circular/genética , ADN de Cadena Simple/genética , Enterococcus faecalis/genética , Técnicas de Transferencia de Gen , Lactococcus lactis/genética , Modelos Genéticos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
This study presents ultrastructural evidence for the presence of a variety of fibril-to-fibril interactions or associations in the architecture of the general matrix of articular cartilage. These interactions are believed to serve a higher purpose of repeatedly constraining an overall radial arrangement of fibrils into an array of oblique interconnecting segments thus creating a three dimensional meshwork within which the hydrated ground substance is constrained. It is argued that any reduction in these interfibrillar interactions will allow the oblique fibril segments to revert to a low energy radial configuration, thus explaining the presence of such arrays prominent in various degenerate forms of articular cartilage.
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Cartílago Articular/ultraestructura , Animales , Cartílago Articular/fisiología , Bovinos , Cabeza Femoral , Congelación , Humanos , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Preservación BiológicaRESUMEN
The construction and function of a model of articular cartilage based on a system of deformable elements trapped within a three-dimensional network of fibrils is described. The network is generated from a radial array of elements appropriately crosslinked along their length. The model demonstrates in a qualitative sense how a soft composite tissue structure such as articular cartilage developed from a specific arrangement of two primary components exhibiting totally contrasting mechanical properties, i.e. tension resisting collagen fibrils and highly deformable hydrated proteoglycans, can have dimensional stability in its unloaded state and mechanical resilience under a wide range of loading conditions.
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Cartílago Articular/anatomía & histología , Modelos Anatómicos , Fenómenos Biomecánicos , Cartílago Articular/fisiología , Colágeno/metabolismo , Elasticidad , Humanos , Proteoglicanos/metabolismo , Estrés MecánicoRESUMEN
In an investigation of the influence of glutaraldehyde fixation pressure and subsequent valve constraint on the coaptive characteristics of porcine aortic valves, 14 valves were examined, eight having been fixed at low pressure (congruent to 1 mm Hg) and six at high pressure (80 mm Hg). The coaptive ratios of the left and right coronary leaflets in the low-pressure-fixed valves showed a significant improvement over those of the same leaflets in the high-pressure-fixed valves. Inflation to 80 mm Hg results in a variable "peeling back" of the coaptive margins of the low-pressure-fixed valves but not of the high-pressure-fixed valves. Comparable coaptive ratios are therefore expected during full inflation of the unconstrained valves fixed both at low pressure and at high pressure. Constraining the low-pressure-fixed valves during inflation to simulate the effect of mounting on a rigid stent produced either a reduction or virtual elimination of this "peeling back" motion or in some instances a slight reversal of the effect, thus increasing the width of the coaptive margin. Hence it is expected that the stented low-pressure-fixed valve will manifest better coaptation than the high-pressure-fixed valve. Finally, the experimental findings of this study, combined with the improved mechanical function of the leaflet tissue already known to occur in the low-pressure-treated valves, provide a convincing case for valve fixation to be carried out under lower pressures.