Investigation phytochimique d'une brosse à dents africaine Zanthoxylum zanthoxyloides (Lam.) Zepernick et Timler (Syn. Fagara zanthoxiloides L.) (Rutaceae)

Résumé: Dans le but de rechercher de nouveaux composés naturels à intérêt thérapeutique, les extraits dichlorométhanique et méthanolique de Zanthoxylum zanthoxyloides (Lam.) Zepernick et Timler (Syn. Fagara zanthoxyloides L.) (Rutaceae), une brosse à dents africaine ont été soumis à un criblage chimique et biologique. Un dépistage des activités: antifongiques contre le champignon phytopathogène Cladosporium cucumerinum et la levure commensale responsable de mycoses chez l'homme Candida albicans, antibactérienne contre la bactérie opportuniste Bacillus subtilis, larvicide contre le moustique vecteur de la fièvre jaune Aedes aegypti et molluscicide contre Biomphalaria glabrata, un escargot impliqué dans la transmission de la schistosomiase urinaire a été réalisé. Les propriétés antiradicalaires et inhibitrices de l'acétylcholinestérase de ces extraits ont aussi été dépistées. Sur la base des résultats obtenus lors de ce screening, l'investigation phytochimique de ces extraits a été entreprise. Elle a abouti à l'isolement de 14 composés, actifs pour la majorité contre Cladosporium cucumerinum et Bacillus subtilis, dont la structure a été établie au moyen de méthodes spectroscopiques (UV, MS, IR, 1H- et 13C-NMR). Des méthodes chimiques (hydrolyse, acétylation) ont été requises pour la confirmation de structures. L'extrait dichlorométhanique a fourni un nouveau composé, un dérivé du phényléthane, ainsi que dix composés connus, dont trois dérivés du phénylpropane, un lignane, un alcaloïde de la famille des benzophénanthridines, un triterpène, deux amides phénoliques et deux amides oléfmiques. L'extrait méthanolique a fourni un nouveau composé avec une fonction endoperoxyde, qui avait montré une activité inhibitrice modérée de l'acétylcholinestérase, ainsi que l'hespéridine et un dérivé de la chélérythrine. Par ailleurs, l'analyse LC/UV/APC1-MS de cet extrait a permis de détecter on-une sept produits connus. Parmi ces composés, se trouvent l'acide divanilloylquinique, la chélérythrine et quatre de ses dérivés: norchélérythrin.e, 6-(2-oxybutyl) dihydrochélérythrine, 6-hydroxy-dihydrochélérythrine et avicine, ainsi qu'une amide phénolique, l'amottianamide. La présence de ces dérivés de la chélérythrine a été mise en évidence dans deux autres espèces du même genre lors d'une étude LC/UV/APCI-MS comparative. Les activités fongicides contre Cladosporium cucumerinum et Candida albicans et bactéricides contre Bacillus subtilis et Streptococcus mutans ATCC 25175, mises en évidence sur plaque CCM et par les tests de dilution dans l'agar de ces composés, permettent de justifier l'utilisation de Zanthoxylum zanthoxyloides (Lam.) Zepemick et Timler comme brosse à dents africaine. Les techniques couplées de pointe utilisées dans cette étude ont montré leur apport inestimable dans le domaine de la recherche phytochimique et les applications futures dans le domaine de déréplication d'extraits bruts. Abstract: With the aim of discovering new natural therapeutics, the dichloromethane and methanol extracts of the African toothbrush tree Zanthoxylum zanthoxyloides (Lam.) Zepernick et Timler (Syn. Fagara zanthoxyloides L.) (Rutaceae), were submitted to biological and chemical assays. The former included: the antifimgal activities of the extracts against the phytopathogenic fungus Cladosporium cucumerinum, the commensal yeast which causes human mycoses Candida albicans, the bactericidal activity against the opportunistic bacteria Bacillus subtilis, the larvicidal activity against the yellow fever-transmitting mosquito Aedes aegypti and the molluscicidal effect on the snail Biomphalaria glabrata involved in the transmission of urinary schistosomiasis. The antiradical and acetylcholinesterase-inhibiting properties of these extracts were also investigated. On the basis of these results, a phytochemical investigation of the dichloromethane and methanol extracts of Zanthoxylum zanthoxyloides was undertaken. Their fractionation led to the isolation of 14 compounds, the majority of which were active against Cladosporium cucumerinum and Bacillus subtilis, whose structures were elucidated by spectroscopic techniques (UV, MS, IR, 1H- and 13C-NMR). Chemical methods (hydrolysis, acetylation) were performed to confirm the structures. The dichloromethane extract yielded a new phenylethane derivative, together with ten known compounds: three phenylpropane derivatives, a lignan, a benzophenanthridine alkaloid, a triterpene and four phenolic and olefinic amides. The methanol extract yielded a new compound with an endoperoxide moiety, which showed moderate acetylcholinesterase-inhibiting activity, together with hesperidin and a chelerythrine derivative. Seven more compounds were detected on-line by LC/UV/APCI-MS. Among the compounds detected were divanilloylquinic acid, chelerythrine and four chelerythrine derivatives: norchelerythrine, 6-(2-oxybuty1)-dihydrochelerythrine, 6-hydroxy dihydrochelerythrine and avicine, together with the phenolic amide amottianamide. Most of the chelerythrine derivatives were also found in two other Zanthoxylum species following LC/UV/APCI-MS analysis. The antifungal activities against Cladosporium cucumerinum and Candida albicans and antibacterial activities against Bacillus subtilis and Streptococcus mutans ATCC 25175, may explain the utilization in traditional medicine of the roots of this plant as a toothbrush. The advanced hyphenated techniques used in this study showed their inestimable contribution to the field of phytochemical research and applications in the field of dereplication of crude extracts.

Prevalencia de la discapacidad en España por comunidades autónomas: el papel de los factores individuales y del entorno geográfico en su variabilidad

Fundamento: La prevalencia de discapacidad en la población general presenta una gran variabilidad geográfica, de manera que identificar aquellos factores que pudieran explicarla será importante para la planificación de políticas sociales. En este trabajo se analiza la variabilidad de la discapacidad por comunidades autónomas desde una doble vertiente, los factores individuales y del entorno. Métodos: Los datos proceden principalmente de la Encuesta de Discapacidad, Deficiencias y Estado de Salud de 1999 y del Inebase, ambas del Instituto Nacional de Estadística (INE). Se calculó la prevalencia de discapacidad simple y ajustada por edad de las CCAA. Se analizan los factores individuales asociados a la discapacidad mediante una regresión logística y los factores individuales y de la comunidad autónoma conjuntamente con una regresión logística de dos niveles. Resultados: La prevalencia de discapacidad muestra una diferencia máxima de 5,75 puntos entre las comunidades autónomas. En la regresión logística la comunidad de residencia fue estadísticamente significativa (OR: 3,35 en la de mayor prevalencia respecto a la de menor) junto con otras variables individuales: edad (OR de 40-64= 1,78 OR de 65-79= 1,87 y OR de >79= 3,34), sexo (OR mujer= 0,66), situación laboral (OR sin trabajo=2,25 OR amas casa/estudiante=1,39 y OR otros=2,03), estado de salud (OR regular= 1,69 OR malo/muy malo= 2,05) y enfermedades crónicas (OR 1-3=1,56 OR4-6=1,82 OR>6=2,59). En la regresión de dos niveles las variables individuales explican poca varianza (s=0,261) y ninguna de las variables relativas a las CCAA mejora el modelo. Conclusiones: Las características individuales no explican suficientemente la variabilidad de la discapacidad entre CCAA y no se han identificado variables del entorno que sean significativas.

Efeito do número de ramos produtivos sobre o desenvolvimento da área foliar e produtividade da figueira

O objetivo deste trabalho foi estudar o efeito do número de ramos produtivos sobre o desenvolvimento da área foliar e produtividade de figos verdes do cultivar Roxo de Valinhos. O experimento utilizando plantas de seis anos de idade, foi conduzido de novembro de 2002 a abril de 2003 na Pesagro-RJ, em Campos dos Goytacazes-RJ (21º19'23" de latitude sul, 41º19'40" de longitude oeste, altitude de 20 a 30 m e clima tipo Aw Köppen). Os tratamentos consistiram de plantas conduzidas com 16; 20; 24; 28 e 32 ramos. Utilizou-se do delineamento experimental de blocos ao acaso e cinco repetições. O IAF aumentou linearmente em função do número de ramos produtivos, enquanto a produtividade mostrou um modelo de resposta quadrática aos tratamentos, provavelmente, limitada pelo sombreamento no interior do dossel que reduz a formação de gemas frutíferas. A maior produtividade observada de figos verdes foi obtida quando as plantas foram conduzidas com 24 ramos, sendo que, neste tratamento, a área foliar média de cada planta foi de 6,2 m².

Diseño, aplicación y evaluación de un programa de educación emocional en un centro penitenciario

Introducción. El propósito de este estudio ha sido evaluar la incidencia que, sobre un grupo de internos de un centro penitenciario, ha tenido la aplicación de un programa de educación emocional para la mejora de la conciencia y la regulación emocional. Se pretendía ofrecer a los internos estrategias de regulación emocional que les fueran útiles en el centro penitenciario y a su vez les facilitaran su futura inclusión social. Método. Se ha utilizado un diseño cuasiexperimental de grupo único con grupo control. Para medir las variables se utilizaron distintos instrumentos, entre ellos una adaptación del CEE (GROP, 2001), un caso práctico (planteamiento de una situación generadora de emociones negativas), un análisis de las sanciones durante dos meses y un cuestionario de valoración de las actividades del programa por parte de los participantes. Resultados. Se destaca que la mayoría de ítems del cuestionario aplicado al grupo experimental mejoran después de formarse así como las respuestas dadas en la resolución del caso práctico. Sin embargo no se puede hablar de diferencias significativas en el caso de las sanciones si se compara con el grupo control. También los implicados valoraron positivamente el programa. Discusión. Los resultados manifiestan que la intervención del programa de educación emocional ha contribuido a la mejora de la conciencia y la regulación emocional del grupo experimental.

Increasing prehospital emergency medical service interventions for nursing home residents.

QUESTION: In the ageing European population, the proportion of interventions by the emergency medical services (EMS) for elderly patients is increasing, but little is known about the recent trend of EMS interventions in nursing homes. The aim of this analysis was to describe the evolution of the incidence of requests for prehospital EMS interventions for nursing home residents aged 65 years and over between 2004 and 2013. METHODS: A prospective population-based register of routinely collected data for each EMS intervention in the Canton of Vaud. Linear time trends of incidence of requests to the EMS in nursing homes were calculated and stratified by age categories. RESULTS: The number of ambulance interventions in nursing homes for people aged 65 years and over (65+) increased by 68.9% (1124‒1898) between 2004 and 2013. A significant linear increase of the annual incidence of requests to EMS per 1,000 nursing home residents was found for people aged 65-79 (10.2, 95% confidence interval [CI] 6.2-14.2), 80-89 (16.5, 95% CI 14.0-19.0) and over 90 (12.1, 95% CI 5.8-18.4). EMS interventions in nursing home residents who required an emergency physician increased during the same period by 205.6% (from 106 to 324), representing an increase from 2% to 7% of all emergency physician interventions in the Canton. CONCLUSIONS: Our results confirmed an important increase in the incidence of EMS interventions in nursing homes during the last decade, far exceeding the actual increase of the nursing home population during the same period. This evolution represents an important opportunity to reconsider the EMS missions in the context of an ageing society.

Treatment of type B periprosthetic femur fractures with curved non-locking plate with eccentric holes: Retrospective study of 43 patients with minimum 1-year follow-up.

INTRODUCTION: Periprosthetic femur fracture (PFF) is a serious complication after total hip arthroplasty that can be treated using different internal fixation devices. However, the outcomes with curved non-locking plates with eccentric holes in this indication have not been reported previously. The objectives of this study were to determine: (1) the union rate; (2) the complication rate; (3) autonomy in a group of patients with a Vancouver type B PFF who were treated with this plate. HYPOTHESIS: Use of this plate results in a high union rate with minimal mechanical complications. MATERIALS AND METHODS: Forty-three patients with a mean age of 79 years±13 (41-98) who had undergone fixation of Vancouver type B PFF with this plate between 2002 and 2007 were included in the study. The time to union and Parker Mobility Score were evaluated. The revision-free survival (all causes) was calculated using Kaplan-Meier analysis. The average follow-up was 42 months±20 (16-90). RESULTS: Union was obtained in all patients in a mean of 2.4 months±0.6 (2-4). One patient had varus malunion of the femur. The Parker Mobility Score decreased from 5.93±1.94 (2-9) to 4.93±1.8 (1-9) (P=0.01). Two patients required a surgical revision: one for an infection after 4.5 years and one for stem loosening. The survival of the femoral stem 5 years after fracture fixation was 83.3%±12.6%. CONCLUSION: Use of a curved plate with eccentric holes for treating type B PFF led to a high union rate and a low number of fixation-related complications. However, PFF remains a serious complication of hip arthroplasty that is accompanied by high morbidity and mortality rates. LEVEL OF EVIDENCE: Retrospective study, level IV.

Effect of gibberellic acid and the biostimulant stimulate® on the initial growth of tamarind

Plant growth regulators and biostimulants have been used as an agronomic technique to optimize the production of seedlings in various crops. This study aimed to evaluate the influence of gibberellic acid and the biostimulant Stimulate® on the initial growth of tamarind (Tamarindus indica L.). The experiments were conducted in a nursery with 50% shading, in a randomized block design with five replications and five plants per plot. Thirty eight days after sowing, the leaves were sprayed seven times a day with 0.0 (control), 0.8, 1.6, 2.4 and 3.2 mL of gibberellic acid L-1 aqueous solution and with 0.0 (control), 6.0,12.0, 18.0, and 24.0 mL Stimulate® L-1 aqueous solution. Stem diameter (SD), plant height (PH), longest root length (LRL), shoot dry mass (SDM), root dry mass (RDM) and RDM:SDM ratio were evaluated ninety days after sowing. Variance and regression analysis showed that GA3 at 4% promoted plant growth (height), but had no significant effect on stem diameter, longest root length, shoot and root dry mass and the RDM:SDM ratio. On the other hand, all concentrations of Stimulate® significantly increased plant height and shoot and root dry mass of tamarind seedlings.

Magnetoestratigrafía de las sucesiones cenozoicas de la cuenca de As Pontes(La Coruña, Noroeste de España).

La cuenca terciaria de As Pontes (Noroeste de España), asociada a un corredor de fallas transcurrentes de dirección NW-SE, ha sido datada mediante magnetoestratigrafia, para lo cual se han estudiado un total de cuatro sucesiones magnetoestratigráficas. Las litologías estudiadas han sido sobre todo arcillas aluviales y palustres-lacustres, con un contenido variable de materia orgánica. En total se han desmagnetizado unos 900 especímenes, mediante desmagnetización térmica y por campos alternantes. Los minerales responsables de la magnetización en las rocas estudiadas son la magnetita y los sulfuros de hierro. A partir de los datos paleomagnéticos, se puede establecer que la sedimentación en la cuenca comenzó en el cron 10r (parte alta del Starnpiense) y se prolongó, como mínimo, hasta el subcron 6AAr.2n (Aquitaniense superior). Así, la duración de la sedimentación en la cuenca fue de unos 6,2 Ma, abarcando desde la última parte del Oligoceno temprano hasta el Mioceno temprano. La correlación magnetoestratigráfica de las diferentes sucesiones de la cuenca ha permitido establecer una correlación cronológica muy precisa a escala de cuenca, determinando la casi total isocronía de la mayor parte de los diferentes niveles de lignito y de las unidades litoestratigráficas de la cuenca. Por otro lado, las declinaciones medias muestran una rotación de 9'+4' para el relleno sedimentario de la cuenca de As Pontes, en sentido horario con respecto a la declinación del Oligoceno-Mioceno, coherente con el movimiento dextrógiro del corredor de fallas transcurrentes de dirección NW-SE. La datación del registro sedimentario de la cuenca de As Pontes permite establecer que los sistemas de fallas transcurrentes de orientación NW-SE del noroeste de la Península Ibérica fueron fuertemente activos desde la última parte del Oligoceno temprano hasta el Mioceno temprano. La finalización del movimiento principal de estos sistemas de fallas coincidió con el fin de actividad del margen entre la microplaca Ibérica y la placa Europea. Esto implicaría que el final de la actividad tectónica principal coincide en el ofshore y en el onshore del NW peninsular.

Traitement des fractures péri-prothétiques de type B du fémur par une plaque anatomique non verrouillée avec trous excentrés : analyse rétrospective de 43 patients avec un recul minimum de 1 an

La fracture périprothétique du fémur (FPF) représente une complication sérieuse des arthroplasties de hanche. Différents matériels d'ostéosynthèse ont été utilisés pour l'ostéosynthèse des FPFs. Toutefois, aucune étude n'a rapporté les résultats obtenus avec une plaque anatomique non-verrouillée avec des trous excentrés. Les buts de ce travail étaient de présenter 1) le taux de consolidation des FPF traitées par cet implant, 2) les caractéristiques péri-opératoires 3) le taux de complications, et 4) les résultats en terme d'autonomie obtenus après le traitement des FPF du groupe B selon Vancouver avec une plaque anatomique à trous excentrés. Hypothèse L'utilisation de cette plaque permet d'obtenir un taux élevé de consolidation avec un minimum de complications mécaniques. Matériels et Méthodes Quarante-trois patients, d'âge moyen 79 ans ± 13 (41 - 98), qui ont été traités pour une ostéosynthèse d'une FPF de type B selon Vancouver avec cette plaque entre 2002 et 2007 ont été inclus. Les patients ont été classifiées selon les scores ASA et de Charnley. Le temps opératoire, les pertes sanguines chirurgicales, le nombre de transfusion, la durée d'hospitalisation, le délai de consolidation, le lieu de vie ainsi que l'autonomie (score de Parker) ont été évalués. Le taux de survie sans révision a été calculé par la méthode de Kaplan-Meier. Le recul moyen est de 42 mois ± 20 (min - max : 16 - 90). Résultats La consolidation a été obtenue chez tous les patients avec un délai moyen de 2,4 mois ± 0,6 (2-4). 1 patient avec un cal vicieux en varus était à déplorer. Le score de Parker a diminué de 5,93 ± 1,94 (2-9) à 4,93 ± 1,8 (1- 9) (p = 0.01). 2 révisions chirurgicales ont été nécessaires sur la série. Le taux de survie à 5 ans des prothèses après ostéosynthèse de la FPF était de 83,3 % ± 12,6 %. Conclusion Cette plaque anatomique avec trous excentrés permet le traitement des FPF du type B et garantit une consolidation de la fracture avec un faible taux de complications liés à l'ostéosynthèse. Toutefois, les FPF représentent une complication sérieuse des arthroplasties de hanche assortie d'un fort taux de morbidités et de mortalité.

STACK OVERWRITING ATTACKS AND DEFENCES IN UNIX ENVIRONMENT

Työn tarkoituksena on tutkia pinon ylikirjoitukseen perustuvien hyökkäysten toimintaa ja osoittaa kokeellisesti nykyisten suojaustekniikoiden olevan riittämättömiä. Tutkimus suoritetaan testaamalla miten valitut tietoturvatuotteet toimivat eri testitilanteissa. Testatut tuotteet ovat Openwall, PaX, Libsafe 2.0 ja Immunix 6.2. Testaus suoritetaan pääasiassa RedHat 7.0 ympäristössä testiohjelman avulla. Testeissä mitataan sekä tuotteiden kyky havaita hyökkäyksiä että niiden nopeusvaikutukset. Myös erityyppisten hyökkäysten ja niitä vastaan kehitettyjen metodien toimintaperiaatteet esitellään seikkaperäisesti ja havainnollistetaan yksinkertaistetuilla esimerkeillä. Esitellyt tekniikat sisältävät puskurin ylivuodot, laittomat muotoiluparametrit, loppumerkittömät merkkijonot ja taulukoiden ylivuodot. Testit osoittavat, etteivät valitut tuotteet estä kaikkia hyökkäyksiä, joten lopuksi perehdytään myös vahinkojen minimointiin onnistuneiden hyökkäysten varalta.

Directional dominance on stature and cognition in diverse human populations.

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Manifestações esqueléticas da doença de gaucher

A doença de Gaucher é manifestação genética causada pela deficiência da enzima glicocerebrosidase, resultando no acúmulo secundário de glicocerebrosídeos nos órgãos do sistema reticuloendotelial. Apresenta-se sob três formas clínicas distintas, podendo ser rapidamente fatal ou crônica com poucos sintomas. O presente trabalho tem o objetivo de analisar os achados da radiografia simples do esqueleto em 32 pacientes comprovadamente portadores da doença, de ambos os sexos e em diferentes faixas etárias. Foram observadas as seguintes alterações: osteopenia difusa em todos os casos, deformidade em "frasco de Erlenmeyer" em 93,7%, alterações articulares em 40,6%, necrose da cabeça do fêmur e lesões líticas em 28,1%, respectivamente, fratura patológica em 9,3% e necrose da cabeça do úmero em 6,2% dos casos. Estes resultados encontram-se de acordo com as descrições da literatura, demonstrando a importância da radiologia convencional como método complementar no diagnóstico desta enfermidade.

Associations between fruit and vegetable consumption and psychological distress: results from a population-based study.

BACKGROUND: Several studies observed associations of various aspects of diet with mental health, but little is known about the relationship between following the 5-a-day recommendation for fruit and vegetables consumption and mental health. Thus, we examined the associations of the Swiss daily recommended fruit and vegetable intake with psychological distress. METHODS: Data from 20,220 individuals aged 15+ years from the 2012 Swiss Health Survey were analyzed. The recommended portions of fruit and vegetables per day were defined as 5-a-day (at least 2 portions of fruit and 3 of vegetables). The outcome was perceived psychological distress over the previous 4 weeks (measured by the 5-item mental health index [MHI-5]). High distress (MHI-5 score ≤ 52), moderate distress (MHI-5 > 52 and ≤ 72) and low distress (MHI-5 > 72 and ≤ 100) were differentiated and multinomial logistic regression analyses adjusted for known confounding factors were performed. RESULTS: The 5-a-day recommendation was met by 11.6 % of the participants with low distress, 9.3 % of those with moderate distress, and 6.2 % of those with high distress. Consumers fulfilling the 5-a-day recommendation had lower odds of being highly or moderately distressed than individuals consuming less fruit and vegetables (moderate vs. low distress: OR = 0.82, 95 % confidence interval [CI] 0.69-0.97; high vs. low distress: OR = 0.55, 95 % CI 0.41-0.75). CONCLUSIONS: Daily intake of 5 servings of fruit and vegetable was associated with lower psychological distress. Longitudinal studies are needed to further determine the causal nature of this relationship.

High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013.

BACKGROUND & AIMS: The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. METHODS: We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. RESULTS: Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV-infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. CONCLUSIONS: Over the last 13years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver-related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.