Microbial mats as model to decipher climate change effect on microbial communities through a mesocosm study.

Marine environments are expected to be one of the most affected ecosystems by climate change, notably with increasing ocean temperature and ocean acidification. In marine environments, microbial communities provide important ecosystem services ensuring biogeochemical cycles. They are threatened by the modification of environmental parameters induced by climate change that, in turn, affect their activities. Microbial mats, ensuring important ecosystem services in coastal areas, are well-organized communities of diverse microorganisms representing accurate microbial models. It is hypothesized that their microbial diversity and metabolic versatility will reveal various adaptation strategies in response to climate change. Thus, understanding how climate change affects microbial mats will provide valuable information on microbial behaviour and functioning in changed environment. Experimental ecology, based on mesocosm approaches, provides the opportunity to control physical-chemical parameters, as close as possible to those observed in the environment. The exposure of microbial mats to physical-chemical conditions mimicking the climate change predictions will help to decipher the modification of the microbial community structure and function in response to it. Here, we present how to expose microbial mats, following a mesocosm approach, to study the impact of climate change on microbial community.

Detección de posible SCACEST (síndrome coronario agudo con elevación del st) mediante KARDIA 6l en la farmacia comunitaria / Detection of possible STEACS (st-elevation acute coronary syndrome) by KARDIA 6l in community pharmacy

PRESENTACION DEL CASO/ANTECEDENTES: Varón, 58 años, fumador activo, hipertenso, dislipémico, diabético insulino-dependiente. De vacaciones en nuestra Comunidad Autónoma, acude a nuestra farmacia refiriendo sensación de atragantamiento, falta de aire y nauseas de 2 horas de evolución, síntomas que van en ascenso, decidiendo consultar en la farmacia por la facilidad para el acceso a la misma y la saturación del Servicio de Urgencias en ese momento.TRATAMIENTO: irbesartan/HCTZ 300mg/25mg (1-0-0); pitavastatina 1 mg (0-0-1); metformina/sitagliptina 1000mg/50 mg (1-0-1); insulina glargina (Lantus) (0-0-18 UI); omeprazol 20 mg (1-0-0).EVALUACION: Tomamos Tensión Arterial: 170/95 mm Hg y realizamos electrocardiograma (ECG) con KARDIA de 6 canales con los siguientes hallazgos: ECG rítmico con QRS ancho y llamativa desnivelación del ST compatible con SCACEST. Al no disponer del resto de derivaciones no se puede asegurar la localización, pero impresiona de infero- posterior.El KARDIA es un monitor portátil de ECG ampliamente validado y único aprobado por la FDA que permite realizar ECG de 1 o 6 derivaciones según el modelo y muy útil como herramienta para detectar arritmias.INTERVENCION: Contactamos con el 061 que acude a la farmacia. Activan CÓDIGO INFARTO.- Administran AAS + ticagrelor + solinitrina iv.-Traslado de Emergencia a la Unidad de Hemodinámica del Hospital General.RESULTADO/SEGUIMIENTO: Yras varios días de ingreso en cardiología es dado de alta con el siguiente tratamiento: Irbesartan/HCTZ 300mg/25 mg (1-0-0); atorvastatina 80 mg (0-0-1); metformina/sitagliptina 1000mg/50 mg (1-0- 1); insulina glargina (Lantus) (0-0-18 UI); omeprazol 20 mg (1-0-0); AAS 100 mg (0-1-0); ticagrelor 90 mg (1-0-1); bisoprolol 2.5 mg (1-0-0). (AU)

Detección de episodio recurrente de fibrilación auricular silente en farmacia comunitaria / Detection of recurrent silent atrial fibrillation in community pharmacies

PRESENTACIÓN DEL CASO: paciente varón, de 68 años, bebedor habitual de 2-3 litros de cervezas diarias, asintomático en el momento actual. El paciente refiere estar anticoagulado con NACO (edoxaban 60 mg (1-0-0)), comenta haber sido cardiovertido eléctricamente hace algo más de un año por episodio de palpitaciones en el contexto de Fibrilación Auricular (FA) rápida de cronología inferior a 24 horas y dado de alta en ritmo sinusal, con flecainida 100 mg (1-0-0) como fármaco mantenedor del ritmo sinusal.EVALUACIÓN: la farmacia pone en marcha un Servicio Profesional Farmacéutico Asistencial (SPFA) de prevención de la enfermedad (detección de enfermedad oculta/riesgo de enfermedad) mediante una campaña gratuita de detección de FA silente. Al paciente le realizamos un electrocardiograma (ECG) con KARDIA de 1 CANAL, monitor portátil de ECG ampliamente validado y único aprobado por la FDA que permite realizar ECG de 1 o 6 derivaciones según el modelo y muy útil como herramienta para detectar arritmias. Se detecta una arritmia de QRS estrecho, no precedidos de Ondas P, con frecuencia ventricular adecuada a 68 sxm (sístoles por minuto): ACxFA (Arritmia Completa por Fibrilación Auricular) con respuesta ventricular adecuada en paciente correctamente anticoagulado y asintomático.INTERVENCION:1. No precisa actuación urgente por nuestra parte dado que es un paciente correctamente anticoagulado y con frecuencia ventricular adecuada en el momento actual. 2. Sí se le aporta el registro del KARDIA para consultar a su Médico de Atención Primaria (MAP) o Cardiólogo de zona en su próxima revisión por si precisa de otras pautas de actuación para evitar la aparición en el futuro de remodelación cardiaca por taqui-miocardiopatía por episodios recurrentes de FA silentes en paciente joven.3. Se le aporta consejo sanitario en relación a la evitación del consumo de alcohol, cardiotóxico conocido. (AU)

Detección de extrasistoles ventriculares y ráfagas de bigeminismo por cardiopatía hipertensiva mediante el uso de kardia 6l en farmacia comunitaria / Detection of ventricular extrasystoles and bigeminy bursts in hypertensive heart disease using kardia 6l in community pharmacies

PRESENTACION DEL CASO/ANTECEDENTES: mujer, 72 años, hipertensa mal controlada, dislipémica, diabética no insulino-dependiente, con mal seguimiento por su Médico de Atención Primaria (MAP) coincidiendo con la pandemia. Acude a nuestra farmacia refiriendo palpitaciones y molestias retroesternales inespecíficas, sin clara relación con el esfuerzo, recurrentes en los últimos días y sintomática a su llegada, que ceden durante su estancia en la farmacia. Tratamiento: losartán 100 mg (1-0-0); amlodipino 5 mg (0-0-1); metformina 850 mg (1-1-1), simvastatina 20 mg (0-0-1); famotidina 20 mg (1-0-0).EVALUACIÓN: tomamos Tensión Arterial: 160/85 mm Hg y realizamos electrocardiograma (ECG) con KARDIA6L. Hallazgos: ritmo sinusal con QRS estrecho, extrasístoles ventriculares, inicialmente aisladas y posteriormente bigeminadas. El KARDIA es un monitor portátil de ECG ampliamente validado y único aprobado por la FDA que permite realizar ECG de 1/6 derivaciones según el modelo y muy útil como herramienta para detectar arritmias.INTERVENCIÓN: Aunque el objetivo inicial del KARDIA en la farmacia es la detección de FA silente como causa tratable de isquemia embolígena en cualquier territorio vascular, dados los factores de riesgo cardiovascular de la paciente y la necesidad de descartar cardiopatía hipertensiva +/- isquémica como sustrato de extrasístoles ventriculares frecuentes derivamos a su MAP para valorar interconsulta con Cardiología, por posible PRM de Problema de salud insuficientemente tratado.RESULTADO/SEGUIMIENTO: 1. Queja formal desde el MAP al Distrito Sanitario por realizar un diagnóstico de sospecha y derivarle a la paciente, finalmente sin consecuencia legal. (AU)

Detección de fibrilación auricular silente en farmacia comunitaria / Detection of silent atrial fibrillation in community pharmacies

PRESENTACION DEL CASO/ANTECEDENTES: paciente varón de 70 años, asintomático, refiere ser fumador activo, hipertenso en tratamiento con enalapril 20 mg (1-0-0) con escaso seguimiento por no acudir a controles de salud.EVALUACIÓN: la farmacia pone en marcha un Servicio Profesional Farmacéutico Asistencial (SPFA) de prevención de enfermedad (detección de enfermedad oculta/riesgo de enfermedad) mediante una campaña gratuita de detección de Fibrilación Auricular (FA) silente. Al paciente le realizamos un electrocardiograma (ECG) con KARDIA de 1 CANAL y tomamos Tensión Arterial: 162/91 mm Hg. El KARDIA es un monitor portátil de ECG ampliamente validado y único aprobado por la FDA que permite realizar ECG de 1 o 6 derivaciones según el modelo y muy útil como herramienta para detectar arritmias.Se detecta una arritmia de QRS estrecho, no precedidos de Ondas P, con frecuencia ventricular adecuada a 71 sxm (sístoles por minuto): ACxFA (Arritmia Completa por Fibrilación Auricular) con respuesta ventricular adecuada en paciente no anticoagulado y asintomático.INTERVENCIÓN: tras detectar un PRM de problema de salud insuficientemente tratado, explicamos al paciente el alto riesgo embolígeno de la arritmia auricular que presenta y la necesidad de iniciar anticoagulación de urgencias.Se aconseja acudir al Servicio de Urgencias de zona para valoración y tratamiento por Médico de Urgencias lo antes posible a pesar de encontrarse asintomático.RESULTADO/SEGUIMIENTO: tras ser valorado por el Dispositivo de Urgencias de Atención Primaria es derivado al Servicio de Urgencias del Hospital de referencia para valoración y tratamiento.Es dado de alta con NACO (edoxaban 60 mg (1-0-0)) y un betabloqueante a dosis baja (bisoprolol 5 mg (1-0-0)) y citado de forma reglada para la Unidad de Arritmias del Hospital de referencia. (AU)

Climate change influences chlorophylls and bacteriochlorophylls metabolism in hypersaline microbial mat.

This study aimed to determine the effect of the climatic change on the phototrophic communities of hypersaline microbial mats. Ocean acidification and warming were simulated alone and together on microbial mats placed into mesocosms. As expected, the temperature in the warming treatments increased by 4 °C from the initial temperature. Surprisingly, no significance difference was observed between the water pH of the different treatments despite of a decrease of 0.4 unit pH in the water reserves of acidification treatments. The salinity increased on the warming treatments and the dissolved oxygen concentration increased and was higher on the acidification treatments. A total of 37 pigments were identified belonging to chlorophylls, carotenes and xanthophylls families. The higher abundance of unknown chlorophyll molecules called chlorophyll derivatives was observed in the acidification alone treatment with a decrease in chlorophyll a abundance. This change in pigmentary composition was accompanied by a higher production of bound extracellular carbohydrates but didn't affect the photosynthetic efficiency of the microbial mats. A careful analysis of the absorption properties of these molecules indicated that these chlorophyll derivatives were likely bacteriochlorophyll c contained in the chlorosomes of green anoxygenic phototroph bacteria. Two hypotheses can be drawn from these results: 1/ the phototrophic communities of the microbial mats were modified under acidification treatment leading to a higher relative abundance of green anoxygenic bacteria, or 2/ the highest availability of CO2 in the environment has led to a shift in the metabolism of green anoxygenic bacteria being more competitive than other phototrophs.

Comparative evaluation of field samples using 2 in-clinic assays for heartworm antigen detection in dogs.

Dirofilaria immitis (heartworm) antigen testing is routinely performed in veterinary practices to detect canine heartworm infections. The purpose of this study was to evaluate the performance of two in-clinic assays to detect heartworm antigen on field samples from practices in heartworm endemic regions. Veterinary staff in 3 practices located in the Southern United States performed a side by side comparison of the SNAP® 4Dx® Plus Test (IDEXX) and the VETSCAN FLEX4® Test (Zoetis) on samples from canine patients presented for vector-borne disease screening. Assays were performed according to the manufacturer's instructions. The remaining plasma sample was submitted for confirmatory testing using the PetChek® Heartworm Test (IDEXX) including immune complex dissociation (ICD) by heat treatment. A total of 232 samples were evaluated by the two in-clinic assays and PetChek Test. SNAP 4Dx Plus was significantly more sensitive for the detection of heartworm antigen in this study; sensitivity was 97.4 % for the SNAP 4Dx Plus test and 76.9 % for VETSCAN FLEX4 test (p < 0.01). The specificity of both tests was 99.5 %. This study reveals significant difference in detecting canine heartworm antigen in field samples.

One Health Surveillance: perceived benefits and workforce motivations.

One Health Surveillance (OHS) implements the One Health approach to improving health by collecting data and producing information to support integrated action across the animal health, human health and environment sectors. The purpose of this study was to survey the biosurveillance community to assess its OHS practices and capabilities, its attitudes towards OHS (perceived value), and the factors that motivate its members to implement OHS practices. The authors used a convenience sample of 185 professionals from multiple domains and 44 nations. They examined the extent to which these professionals implemented OHS, gathered their opinions on the value of OHS, assessed their perceptions of the capacity to perform specific OHS tasks and identified their priorities for change. Over 85% of all respondents said that they considered OHS to be beneficial, with no significant differences between work domains or country income groups; over 50% indicated that they already applied OHS. Obtaining access to data collected by other domains was both the most frequent challenge and the most difficult to improve. The highest priority for improvement was having the ability to send and receive electronic data. Respondents from low-income or middle-income countries were more motivated to make improvements than stakeholders from high-income countries. These findings provide a snapshot of current opinions and practices and, together with suggestions for improvements from professionals in the field, can help to target priority needs for OHS information, training and resources.

La surveillance Une seule santé opérationnalise la méthode Une seule santé pour une meilleure santé à travers la collecte de données et la production d'informations visant à soutenir la mobilisation transversale des secteurs de la santé animale, de la santé publique et de la santé environnementale en vue d'une action intégrée. Les auteurs présentent les résultats d'une enquête menée auprès des professionnels en charge de la biosurveillance afin d'évaluer leurs pratiques et capacités en matière de surveillance Une seule santé, leurs attitudes à l'égard de cette surveillance (c'est-à-dire leur perception de l'intérêt de la démarche) et les facteurs susceptibles de les motiver à la mettre en oeuvre. Les auteurs ont procédé à un échantillonnage de commodité de 185 intervenants issus de plusieurs secteurs dans 44 pays. Ils ont ensuite analysé le niveau de mise en oeuvre de la surveillance Une seule santé chez ces intervenants, recueilli leurs opinions concernant l'intérêt de la démarche, évalué la perception qu'ils avaient de leur capacité à mener à bien certaine tâches spécifiques dans ce domaine et identifié leurs priorités en vue du changement. Plus de 85 % des répondants ont déclaré considérer la surveillance Une seule santé comme étant bénéfique, résultat ne présentant pas de corrélation significative avec le secteur professionnel des personnes interrogées ni avec le niveau de revenu de leur pays ; plus de 50 % des répondants ont par ailleurs indiqué qu'ils appliquaient déjà les principes d'une surveillance Une seule santé. La difficulté la plus fréquente et qui paraissait la plus difficile à résoudre était celle de pouvoir accéder aux données enregistrées par d'autres secteurs. La première des priorités identifiées en vue d'une amélioration concernait la capacité d'envoyer et de recevoir des données électroniques. La motivation à introduire des améliorations était plus forte chez les répondants des pays à revenu faible ou intermédiaire que chez les parties prenantes des pays à revenus élevés. Ces résultats, qui offrent un instantané des opinions et des pratiques actuelles assorti de propositions concrètes d'amélioration formulées par les professionnels de terrain devraient pouvoir contribuer à cibler les besoins prioritaires en matière d'information, de formation et de ressources dédiées à la surveillance Une seule santé.

Practicar la vigilancia en clave de Una sola salud significa traducir esta idea en la práctica con el fin de mejorar la salud reuniendo datos y generando información a partir de la cual actuar de forma integrada en los sectores de la sanidad animal, la salud humana y el medio ambiente. Los autores describen un estudio de los círculos dedicados a la vigilancia biológica que tenía por objetivo evaluar sus procedimientos y capacidades de vigilancia en clave de Una sola salud, sus actitudes al respecto (valor atribuido) y los factores que los motivan a instaurar procedimientos concebidos desde la lógica de Una sola salud. Para ello los autores utilizaron una muestra de conveniencia de 185 profesionales de múltiples disciplinas y 44 países. Tras determinar en qué medida esos profesionales practicaban la vigilancia en clave de Una sola salud, les pidieron su opinión sobre la utilidad de este tipo de vigilancia, evaluaron la capacidad que subjetivamente se atribuían de efectuar labores específicas de vigilancia en clave de Una sola salud y determinaron aquellos cambios que esas personas juzgaban prioritarios. Más de un 85% de los encuestados dijo considerar beneficiosa la vigilancia en clave de Una sola salud, sin que se observaran diferencias significativas por ámbito de trabajo o por países según el grupo de ingresos. Más de un 50% afirmó que ya aplicaba este tipo de vigilancia. El problema señalado con más frecuencia y juzgado a la vez más difícil de resolver era el del acceso a datos obtenidos desde otros ámbitos de trabajo. El aspecto que más urgía mejorar era el de la capacidad de enviar y recibir datos electrónicos. Los encuestados de países de nivel bajo o medio de ingresos mostraban mayor motivación a la hora de introducir mejoras que sus homólogos de países de ingresos altos. Estas conclusiones, que ofrecen una «instantánea¼ de las opiniones y prácticas imperantes, pueden ayudar, junto con las propuestas de mejora procedentes de esos profesionales que trabajan sobre el terreno, a seleccionar las necesidades prioritarias de información, formación y recursos para la práctica de la vigilancia en clave de Una sola salud.

Modelling the functioning of a coupled microphytobenthic-EPS-bacterial system in intertidal mudflats.

A mechanistic and biogeochemical model was developed to analyze the interactions between microphytobenthos (MPB), bacteria and nutrients in a tidal system. Behavioral vertical migration was hypothesized as being controlled by exogenous factors (tide and light) but also by endogenous factors (carbon and nitrogen requirements). The secretion of Extracellular Polymeric Substances (EPS) during photosynthesis (overflow metabolism) and migration of diatoms was also formulated. Similarities in MPB dynamics between observations and simulations support the assumption that carbon and nitrogen ratios are additional key processes behind the vertical migration of diatoms in the sediment. The model satisfactorily reproduced the three growth phases of the MPB development observed in a mesocosm (the lag phase, the logarithmic growth, and the plateau). Besides, nutrient availability, which could be induced by faunal bioturbation, significantly determined the extent of MPB biomass and development. The plateau phase observed in the last days of simulations appeared to be attributed to a nutrient depletion in the system, emphasizing the importance of nutrient availability. The model, although improvable especially on the formulation of the EPS excretion and bacteria development, already updated understanding of several aspects of benthic-system functioning during experimental conditions.

Reactive oxygen species and NADPH oxidase 4 involvement in osteoarthritis.

Osteoarthritis (OA) is a degenerative chronic disease affecting >300,000 million people around the world as of 2016. Symptomatic measures exist, but there are hardly any curative treatments available. Disruption of the cartilage homeostasis in favor of catabolism leads to cartilage destruction. ROS-macromolecular-induced damage is significantly greater in OA cartilage and OA is described as low-grade chronic systemic inflammation. This review aimed to assess the critical role of cartilage ageing and oxidative stress in the OA process, focusing in particular on NADPH oxidase and especially Nox4 involvement. With age, hypertrophic senescent cells with an altered redox cell profile accumulated. Chondrocytes are more sensitive to oxidant-mediators and the serum level of pro-inflammatory mediators increases. Age-related advanced glycation end products impact on extra cellular matrix (ECM) properties leading to the apoptosis of chondrocytes. A focus on NADPH oxidase-mediated-ROS signaling highlighted the very specific Nox4 isoform, which plays a role on the final common pathway targeting chondrocyte cells. IL-1ß-mediated Nox4 stimulation induced an increase in the levels released by the chondrocyte of MMP-1 and MMP-13 proteins, which are involved in ECM degradation. In comparison with the other Nox isoforms, Nox4 remains unusual, since it is constitutively active, does not depend on cytosolic activator proteins and seems to generate H2O2 thanks to the specific conformation of the Nox4 E-loop. Nox4-induced ROS production appears an essential actor in the OA process and it could be relevant to focus on this target in the aim of discovering and developing new therapeutic strategies.

Diel Rhythm Does Not Shape the Vertical Distribution of Bacterial and Archaeal 16S rRNA Transcript Diversity in Intertidal Sediments: a Mesocosm Study.

In intertidal sediments, circadian oscillations (i.e., tidal and diel rhythms) and/or depth may affect prokaryotic activity. However, it is difficult to distinguish the effect of each single force on active community changes in these natural and complex intertidal ecosystems. Therefore, we developed a tidal mesocosm to control the tidal rhythm and test whether diel fluctuation or sediment depth influence active prokaryotes in the top 10 cm of sediment. Day- and nighttime emersions were compared as they are expected to display contrasting conditions through microphytobenthic activity in five different sediment layers. A multiple factor analysis revealed that bacterial and archaeal 16S ribosomal RNA (rRNA) transcript diversity assessed by pyrosequencing was similar between day and night emersions. Potentially active benthic Bacteria were highly diverse and influenced by chlorophyll a and phosphate concentrations. While in oxic and suboxic sediments, Thaumarchaeota Marine Group I (MGI) was the most active archaeal phylum, suggesting the importance of the nitrogen cycle in muddy sediments, in anoxic sediments, the mysterious archaeal C3 group dominated the community. This work highlighted that active prokaryotes organize themselves vertically within sediments independently of diel fluctuations suggesting adaptation to physicochemical-specific conditions associated with sediment depth.

IL-1beta mediates MMP secretion and IL-1beta neosynthesis via upregulation of p22(phox) and NOX4 activity in human articular chondrocytes.

OBJECTIVES: Osteoarthritis (OA) is characterized by a progressive alteration of the biochemical properties of the articular cartilage. Inflammation plays a major role in OA, particularly through the cytokine Interleukine-1ß, promoting reactive oxygen species (ROS) generation and matrix metalloproteinases (MMP) synthesis by the chondrocytes, orchestrating matrix proteolysis. NADPH oxidases (NOX) are membrane enzymes dedicated to the production of ROS. Role of oxidative stress is well established in OA; however, contribution of NOX in this process is still poorly documented. In this study, we addressed the role of NOX in primary human articular chondrocytes (HAC) upon inflammatory conditions--namely IL-1ß and OA. DESIGN: HAC were collected from patients undergoing hip surgery. Chondrocytes were treated with IL-1ß and NOX inhibitors Diphenylene Iodonium, GKT136901, Tiron and Heme oxygenase-1 before MMP expression and NOX activity assessment. Finally, NOX4 expression was compared between OA and non OA parts of hip cartilage (n = 14). RESULTS: This study establishes for the first time in human that NOX4 is the main NOX isoform expressed in chondrocytes. We found a significant upregulation of NOX4 mRNA in OA chondrocytes. Expression of NOX4/p22(phox) as well as ROS production is enhanced by IL-1ß. On the other hand, the use of NOX4 inhibitors decreased IL-1ß-induced collagenase synthesis by chondrocytes. Moreover, our study support the existence of a redox dependant loop sustaining pro-catabolic pathways induced by IL-1ß. CONCLUSIONS: This study points out NOX4 as a new putative target in OA and suggests that NOX-targeted therapies could be of interest for the causal treatment of the pathology.

Intravitreal dexamethasone implant versus anti-VEGF injection for treatment-naïve patients with retinal vein occlusion and macular edema: a 12-month follow-up study.

PURPOSE: The objective of his study was to compare the visual and anatomical outcomes in treatment-naïve patients with macular edema secondary to retinal vein occlusion after intravitreal injections of dexamethasone implants (DEX) and anti-VEGF. METHODS: One hundred two patients (64 in the anti-VEGF group, 38 in the DEX group) without previous treatment were included in this multi-center retrospective study and evaluated at baseline and 1, 3, 6, and 12 months after the onset of treatment. Patients were defined as "good responders" if central macular thickness (CMT) was less than or equal to 250 µm in TD-OCT or 300 µm in SD-OCT after the injections. RESULTS: At month 3 (n = 102), BCVA had increased significantly, by 0.1 ± 0.3 logMAR in the anti-VEGF group (p = 0.04) and 0.4 ± 0.4 logMAR in the DEX group (p < 0.001); the difference between the two groups was statistically significant (p = 0.007). CMT decreased significantly, by 138 ± 201 µm (-19 %, p < 0.001) in the anti-VEGF group and 163 ± 243 µm (-21 %, p < 0.001) in the DEX group. After 3 months, five patients (13 %) in the DEX group and 20 (31 %) in the anti-VEGF group (p < 0.001) changed treatment. Among the 77 patients who did not switch from their initial treatment, no significant functional or anatomical difference between the two groups was observed at months 6 and 12. Elevation of intraocular pressure > 21 mmHg was more frequent in the DEX group (21 %) than in the anti-VEGF group (3 %, p = 0.008). CONCLUSIONS: Visual acuity recovery was better in the DEX group than in the anti-VEGF group at month 3, but with no difference in CMT. In patients who did not change treatment, the long-term anatomical and visual outcome was similar between the DEX and anti-VEGF groups.

Pilot simulation study using meat inspection data for syndromic surveillance: use of whole carcass condemnation of adult cattle to assess the performance of several algorithms for outbreak detection.

The objective of this study was to assess the performance of several algorithms for outbreak detection based on weekly proportions of whole carcass condemnations. Data from one French slaughterhouse over the 2005-2009 period were used (177 098 slaughtered cattle, 0.97% of whole carcass condemnations). The method involved three steps: (i) preparation of an outbreak-free historical baseline over 5 years, (ii) simulation of over 100 years of baseline time series with injection of artificial outbreak signals with several shapes, durations and magnitudes, and (iii) assessment of the performance (sensitivity, specificity, outbreak detection precocity) of several algorithms to detect these artificial outbreak signals. The algorithms tested included the Shewart p chart, confidence interval of the negative binomial model, the exponentially weighted moving average (EWMA); and cumulative sum (CUSUM). The highest sensitivity was obtained using a negative binomial algorithm and the highest specificity with CUSUM or EWMA. EWMA sensitivity was too low to select this algorithm for efficient outbreak detection. CUSUM's performance was complementary to the negative binomial algorithm. The use of both algorithms on real data for a prospective investigation of the whole carcass condemnation rate as a syndromic surveillance indicator could be relevant. Shewart could also be a good option considering its high sensitivity and simplicity of implementation.

Validation of a new tool: the calorie intake tool, to easily estimate the energy intake of diseased aged patient.

OBJECTIVE: The aim of the study was to validate the Calorie Intake Tool (CIT), a new tool to estimate energy intake. DESIGN, SETTING AND PATIENTS: 100 patients older than 75 were randomly selected in seven geriatric units at Toulouse University Hospital. MEASUREMENTS: Energy intake was calculated for each subject with the CIT and by weighing the food consumed. RESULTS: Total calorie intake did not differ significantly between the two methods, 1318 ± 586 for CIT and 1353 ± 625 for food weighing. The Intraclass Correlation coefficient (ICC) was higher than 0.89 for total calorie intake and the Bland and Altman analysis was consistent with these results and showed a bias for high calorie intake (mean error 35 ± 420 kcal). CONCLUSION: The study shows that the CIT for the evaluation of calorie intake in elderly diseased patients is valid against the reference method (weighing the food consumed).

Hospital and ambulatory management, and compliance to treatment in HIV infection: regional health insurance agency analysis.

OBJECTIVE: We had for objective to study HIV management (hospital, ambulatory, and mixed) and assess compliance with health insurance database. METHOD: We conducted a retrospective study using the French Social Security (CPAM) database. The inclusion criteria were: age>18years of age, at least 2 prescriptions of antiretroviral therapy. RESULTS: Five hundred and seventy-five patients were included: extra-hospital (12), hospital (162), mixed (401). The prescriptions were exclusively hospital issued for 76.2% of the patients. Among the mixed group patients, 91% of treatments were delivered at least once in the community, and 45.6% of biological tests were performed in private laboratories at least once. The sex ratio (2.1 vs. 1.3), the number of patients having switched antiretroviral therapy (36.7% vs. 27.8%), and the frequency of biological tests (3.1 vs. 2.6) were significantly higher in the mixed group compared to the hospital group. The mean compliance was 90% in the hospital group and 91.8% in the mixed group. The compliance was<80% for 104 patients (21.8%). Patients with≥80% compliance were older (46.1years of age vs. 42.7years of age), with more frequent biological tests (3 per year vs. 2.5 per year), and more frequent switches in treatment (35.4% vs. 26.0%). CONCLUSION: Prescriptions of ARV were almost exclusively hospital issued. Their dispensation and biological tests were split between hospital and extra-hospital settings. Most patients demonstrated an optimal compliance. The CPAM database allows describing HIV management and assessing compliance.

MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

OBJECTIVE: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). DESIGN PATIENTS: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). INTERVENTIONS: 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. BASELINE POPULATION: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Dietary vitamin D intake and muscle mass in older women. Results from a cross-sectional analysis of the EPIDOS study.

OBJECTIVES: Vitamin D intake may prevent physical performance decline through prevention of muscle mass loss. Our objective was to determine whether low dietary intakes were associated with low muscle mass (MM). DESIGN AND PARTICIPANTS: Cross-sectional analysis of 1989 community-dwelling women (mean age 80.5±3.8years) from the EPIDémiologie de l'OStéoporose (EPIDOS) study were assessed at baseline. MEASUREMENTS: Low intakes of vitamin D (<70µg/week) were estimated from the weekly dietary vitamin D intakes (self-administered food frequency questionnaire). Low MM was defined according to the appendicular skeletal muscle mass index assessed using Dual Energy X-ray Absorptiometry, divided by square height of less than 5.45 kg/m2. Usual gait speed defined physical performance. Age, sun exposure, co-morbidities, education level, living arrangements, recreational physical activity, dietary protein and calcium intakes, bone mineral density, handgrip strength, and body mass index were considered as potential confounders. Multivariate logistic regression analyses assessed the association between low vitamin D intakes and low MM. RESULTS: Two-hundred and nine (10.5%) women with low MM were compared to 1,780 women with normal MM. In final model, obesity/overweight (Adjusted Odds Ratios, aOR=0.09; 95%CI [0.05-0.17]), malnutrition (aOR=3.90; 95%CI [2.74-5.54]) and low handgrip strength (aOR=2.33; 95%CI [1.44-3.77]; p<0.001) were statistically associated with a low MM status. CONCLUSION: No association with low MM has been reported regarding low dietary intakes of vitamin D.

Somatic RAS mutations occur in a large proportion of sporadic RET-negative medullary thyroid carcinomas and extend to a previously unidentified exon.

CONTEXT: Medullary thyroid carcinoma (MTC) is characterized by proto-oncogene RET mutations in almost all hereditary cases as well as in more than 40% of sporadic cases. Recently, a high prevalence of RAS mutations was reported in sporadic MTC, suggesting an alternative genetic event in sporadic MTC tumorigenesis. OBJECTIVE: This study aimed to extend this observation by screening somatic mutational status of RET, BRAF, and the three RAS proto-oncogenes in a large series of patients with MTC. MATERIALS AND METHODS: Direct sequencing of RET (exons 8, 10, 11, 13, 14, 15, 16), BRAF (exons 11 and 15), and KRAS, HRAS, and NRAS genes (exons 2, 3, and 4) was performed on DNA prepared from 50 MTC samples, including 30 sporadic cases. RESULTS: Activating RET mutations were detected in the 20 hereditary cases (germline mutations) and in 14 sporadic cases (somatic mutations). Among the 16 sporadic MTC without any RET mutation, eight H-RAS mutations and five K-RAS mutations were found. Interestingly, nine RAS mutations correspond to mutation hot spots in exons 2 and 3, but the other four mutations were detected in exon 4. The RET and RAS mutations were mutually exclusive. No RAS gene mutation was found in hereditary MTC, and no BRAF or NRAS mutation was observed in any of the 50 samples. CONCLUSIONS: Our study confirms that RAS mutations are frequent events in sporadic MTC. Moreover, we showed that RAS mutation analysis should not be limited to the classical mutational hot spots of RAS genes and should include analysis of exon 4.

ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence.

Activated Ras oncogene induces DNA-damage response by triggering reactive oxygen species (ROS) production and this is critical for oncogene-induced senescence. Until now, little connections between oncogene expression, ROS-generating NADPH oxidases and DNA-damage response have emerged from different studies. Here we report that H-RasV12 positively regulates the NADPH oxidase system NOX4-p22(phox) that produces H(2)O(2). Knocking down the NADPH oxidase with small interference RNA decreases H-RasV12-induced DNA-damage response detected by γ-H2A.X foci analysis. Using HyPer, a specific probe for H(2)O(2), we detected an increase in H(2)O(2) in the nucleus correlated with NOX4-p22(phox) perinuclear localization. DNA damage response can be caused not only by H-RasV12-driven accumulation of ROS but also by a replicative stress due to a sustained oncogenic signal. Interestingly, NOX4 downregulation by siRNA abrogated H-RasV12 regulation of CDC6 expression, an essential regulator of DNA replication. Moreover, senescence markers, such as senescence-associated heterochromatin foci, PML bodies, HP1ß foci and p21 expression, induced under H-RasV12 activation were decreased with NOX4 inactivation. Taken together, our data indicate that NADPH oxidase NOX4 is a critical mediator in oncogenic H-RasV12-induced DNA-damage response and subsequent senescence.