Differential recovery ability from infections by two blood parasite genera in males of a Mediterranean lacertid lizard after an experimental translocation.

Different blood parasites can co-infect natural populations of lizards. However, our knowledge of the host's ability to recover from them (i.e., significantly reduce parasitemia levels) is scarce. This has interest from an ecological immunology perspective. Herein, we investigate the host recovery ability in males of the lizard Psammodromus algirus infected by parasite genera Schellackia and Karyolysus. The role of lizard hosts is dissimilar in the life cycle of these two parasites, and thus different immune control of the infections is expected by the vertebrate host. As Schellackia performs both sexual and asexual reproduction cycles in lizards, we expect a better immune control by its vertebrate hosts. On the contrary, Karyolysus performs sexual reproductive cycles in vectors, hence we expect lower immune control by the lizards. We carried out a reciprocal translocation experiment during the lizards' mating season to evaluate both parasitemia and leukocyte profiles in male lizards, being one of the sampling plots close to a road with moderate traffic. These circumstances provide a combination of extrinsic (environmental stress) and intrinsic factors (reproductive vs. immune trade-offs) that may influence host's recovery ability. We recaptured 33% of the lizards, with a similar proportion in control and translocated groups. Karyolysus infected 92.3% and Schellackia 38.5% of these lizards. Hosts demonstrated ability to significantly reduce parasitemia of Schellackia but not of Karyolysus. This suggests, in line with our predictions, a differential immune relationship of lizards with these parasites, at time that supports that parasites with different phylogenetic origins should be analyzed separately in investigations of their effects on hosts. Furthermore, lizards close to the road underwent a stronger upregulation of lymphocytes and monocytes when translocated far from the road, suggesting a putative greater exposure to pathogens in the latter area.

The role of microglia in 67NR mammary tumor-induced suppression of brain responses to immune challenges in female mice.

It is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain-mediated side effects and higher rates of infection reported in cancer patients. We hypothesized that chronic low-grade peripheral tumor-induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll-like receptor 2 agonist of Percoll-enriched primary microglia cultures was comparable between tumor-bearing and -free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)-1ß injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor-induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly because of an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype.

Fecal glucocorticoid metabolites and ectoparasites as biomarkers of heat stress close to roads in a Mediterranean lizard.

Differences between air and ground temperatures are expected to narrow with the advance of the season in temperate regions (aka seasonal restriction in the availability of thermal microhabitats), which may activate behavioral and physiological responses of ectotherm species adapted to temperate climates. However, according to cost-benefit models of ectotherm thermoregulation, we hypothesize that these responses may also carry some costs. We quantified seasonal shifts in thermoregulatory precision, concentration of fecal glucocorticoid metabolites, and load of ectoparasites in a Mediterranean lizard, Psammodromus algirus. We also tested whether the proximity to a road, a putative source of chronic stress, can facilitate the glucocorticoid-mediated response of lizards to heat stress. As expected, differences between body and environmental temperatures narrowed during the reproductive season and lizards responded by increasing their thermoregulatory precision and the secretion of glucocorticoids, as indicated by metabolites in feces. Interestingly, lizards tended to have higher glucocorticoid concentration when captured far from the road. This might reflect either a putative impairment of the glucocorticoid-mediated response of the lizards to heat stress close to the road or the plastic capability of P. algirus to acclimate to sources of moderate chronic stress. In the latter direction, the increase of both glucocorticoid metabolites and thermoregulatory precision supported that this Mediterranean species responds to environmental thermal restrictions with adaptive behavioral and physiological mechanisms. However, this was also associated with an increase in its susceptibility to ectoparasites, which represents an added cost to the current cost-benefit models of ectotherm thermoregulation.

Neuroimmunology of the female brain across the lifespan: Plasticity to psychopathology.

The female brain is highly dynamic and can fundamentally remodel throughout the normal ovarian cycle as well as in critical life stages including perinatal development, pregnancy and old-age. As such, females are particularly vulnerable to infections, psychological disorders, certain cancers, and cognitive impairments. We will present the latest evidence on the female brain; how it develops through the neonatal period; how it changes through the ovarian cycle in normal individuals; how it adapts to pregnancy and postpartum; how it responds to illness and disease, particularly cancer; and, finally, how it is shaped by old age. Throughout, we will highlight female vulnerability to and resilience against disease and dysfunction in the face of environmental challenges.

Effects of local activation and blockade of dopamine D4 receptors in the spiking activity of the reticular thalamic nucleus in normal and in ipsilateral dopamine-depleted rats.

The reticular thalamic nucleus (RTn) controls the overall activity of thalamo-cortical neurons information processing. GABAergic RTn neurons have one of the highest densities of D4-type dopamine receptors in subcortical structures. The unitary electrical activity of RTn neurons was recorded in vivo in Wistar rats in order to study the effects of local activation and blockade of D4 receptors under both conditions, normal and ipsilateral lesion of the dopaminergic pathways. Our data suggest that: i) there is a tonic dopaminergic input to the RTn; ii) local activation of D4 receptors increases the basal firing rate of RTn neurons in normal and lesioned rats, and iii) local blockade of D4 receptors diminishes the firing rate in normal but not in lesioned rats. Altogether, our findings support that dopamine contributes to the spontaneous basal firing of the RTn neurons through D4-type dopamine receptors.

Effectiveness of an intervention in multicomponent exercise in primary care to improve frailty parameters in patients over 70 years of age (MEFAP-project), a randomised clinical trial: rationale and study design.

BACKGROUND: Physical activity may reverse frailty in the elderly, but we encounter barriers to the implementation of exercise programs in this population. Our main aim is to evaluate the effect of a multicomponent physical activity program, versus regular medical practice, on reverting pre-frailty status among the elderly, 12 months post-intervention. METHODS: Randomized parallel group multicenter clinical trial located in primary care setting, among non-dependent and pre-frail patients > 70 years old, including 190 patients (95 intervention, 95 control group). INTERVENTION: Multicomponent physical activity program (MEFAP, for its acronym in Spanish) with twelve 1.5 h-weekly sessions comprised of: 1. Informative session; 2. Exercises for improving aerobic resistance, muscle strength, propioception-balance and flexibility; and 3. Handing out of at-home exercise chart (twice/week). Main variable: pre-frailty according to the Fried phenotype. Secondary variables: sociodemographic, clinical and functional variables; exercise program adherence, patient satisfaction with the program and quality of life. We will perform an intention-to-treat analysis by comparing the retrogression from pre-frailty (1 or 2 Fried criteria) to robust status (0 Fried criteria) by the end of the intervention, 6 months and 12 months post-intervention. The accumulated incidence in each group will be calculated, as well as the relative risk (RR) and the number needed to treat (NNT) with their corresponding 95% confidence intervals. Protocol was approved by the Ethics Committee Hospital la Paz. DISCUSSION: Within the context of regular clinical practice, our results will provide evidence regarding the effects of exercise interventions on frailty among pre-frail older adults, a key population given their significant potential for functional, physical, and mental health improvement. TRIAL REGISTRATION: NCT03568084 . Registered 26 June 2018. Date of enrollment of the first participant to the trial: July 2nd 2018.

Hatching asynchrony vs. foraging efficiency: the response to food availability in specialist vs. generalist tit species.

Breeding mistiming is increasingly frequent in several ecosystems in the face of current climate change. Species belonging to higher trophic levels must employ mechanisms to reduce it. One of these mechanisms is hatching asynchrony, with the eggs in a clutch hatching over a period of several days. Some authors have suggested it to be adaptive when food is unpredictable. However, these birds can also suffer associated costs. We tested whether a species with higher foraging efficiency avoid hatching asynchrony compared to its sister species. We studied hatching asynchrony and nestling provisioning in relation to food availability in sympatric populations of blue and great tits. For the first time, we show that sister species respond to food availability with different strategies. Blue tit feeding rates readily responded to the abundance of their main prey, and also reduced the impact of nestling size hierarchy on mean nestling weight, consequently increasing fledging rate. Our results suggest that levels of hatching asynchrony seem to be influenced by species-specific life history traits, as generalist foragers rely less on it. They also highlight the importance of multi-species approaches when studying the response of organisms to environmental unpredictability.

The influence of landscape configuration and environment on population genetic structure in a sedentary passerine: insights from loci located in different genomic regions.

The study of the factors structuring genetic variation can help to infer the neutral and adaptive processes shaping the demographic and evolutionary trajectories of natural populations. Here, we analyse the role of isolation by distance (IBD), isolation by resistance (IBR, defined by landscape composition) and isolation by environment (IBE, estimated as habitat and elevation dissimilarity) in structuring genetic variation in 25 blue tit (Cyanistes caeruleus) populations. We typed 1385 individuals at 26 microsatellite loci classified into two groups by considering whether they are located into genomic regions that are actively (TL; 12 loci) or not (NTL; 14 loci) transcribed to RNA. Population genetic differentiation was mostly detected using the panel of NTL. Landscape genetic analyses showed a pattern of IBD for all loci and the panel of NTL, but genetic differentiation estimated at TL was only explained by IBR models considering high resistance for natural vegetation and low resistance for agricultural lands. Finally, the absence for IBE suggests a lack of divergent selection pressures associated with differences in habitat and elevation. Overall, our study shows that markers located in different genomic regions can yield contrasting inferences on landscape-level patterns of realized gene flow in natural populations.

Neuroinflammation in the normal aging hippocampus.

A consequence of normal aging is a greater susceptibility to memory impairments following an immune challenge such as infection, surgery, or traumatic brain injury. The neuroinflammatory response, produced by these challenges results in increased and prolonged production of pro-inflammatory cytokines in the otherwise healthy aged brain. Here we discuss the mechanisms by which long-lasting elevations in pro-inflammatory cytokines in the hippocampus produce memory impairments. Sensitized microglia are a primary source of this exaggerated neuroinflammatory response and appear to be a hallmark of the normal aging brain. We review the current understanding of the causes and effects of normal aging-induced microglial sensitization, including dysregulations of the neuroendocrine system, potentiation of neuroinflammatory responses following an immune challenge, and the impairment of memories. We end with a discussion of therapeutic approaches to prevent these deleterious effects.

Enhanced male coloration after immune challenge increases reproductive potential.

In many animal species, females select a mate on the basis of the expression of secondary sexual traits. A prevalent theory suggests that male ornaments are reliable indicators of immunocompetence, because the cost of immune function prevents cheating. However, sexual signalling is a component of male reproductive effort, and an immune challenge may also alter his perceived future prospects and hence signalling effort. In this study, blue-footed booby males (Sula nebouxii) were inoculated with a diphtheria-tetanus vaccine during courtship to investigate the consequences of mounting an immune response on signalling effort. We found that, after this immune challenge, on average, males increased their signalling effort but lost more body mass compared with control males. Importantly, vaccination affected the partner's reproductive decisions: compared with control females, females paired with vaccinated males laid eggs earlier and increased clutch volume in pairs that laid early. Overall, our results suggest that blue-footed booby males invest more in sexual signals when future breeding opportunities are at risk, eliciting a greater reproductive investment by their partners. Increased signalling effort by infected individuals may contrast the idea of sexual ornaments as signals of infection status.

Wildlife reservoirs of brucellosis: Brucella in aquatic environments.

Neurobrucellosis and osteomyelitis are common pathologies of humans and cetaceans infected with Brucella ceti or B. pinnipedialis. Currently, 53 species of marine mammal are known to show seropositivity for brucellae, and B. ceti or B. pinnipedialis have been isolated or identified in polymerase chain reaction assays in 18 of these species. Brucellae have also been isolated from fish and identified in lungworm parasites of pinnipeds and cetaceans. Despite these circumstances, there are no local or global requirements for monitoring brucellosis in marine mammals handled for multiple purposes such as capture, therapy, rehabilitation, investigation, slaughter or consumption. Since brucellosis is a zoonosis and may be a source of infection to other animals, international standards for Brucella in potentially infected marine mammals are necessary.

Evaluación de la efectividad de una intervención educativa para disminuir el peso de la mochila escolar en los alumnos de 3. ° y 4. ° de educación primaria / Evaluation of effectiveness of an educational intervention to decrease school backpack weight in 3rd and 4th year primary school children

Introducción El trabajo demuestra que una intervención educativa en las aulas, realizada por un fisioterapeuta, reduce el peso de las mochilas que deben transportar los escolares de 8 a 10 años. Conseguir que el peso de la mochila no supere el 10-15% del peso total del alumno evita la sobrecarga de la columna vertebral y, por tanto, uno de los factores de riesgo de presentar vertebrales. Cargas superiores modifican la curvatura espinal con una percepción de aumento de esfuerzo y aparición de dolor. Material y método Diseño: tipo ensayo clínico controlado aleatorizado abierto. Emplazamiento: colegios públicos de Alcobendas y San Sebastián de los Reyes. Participantes: un total de 357 niños entre 8 y 10 años. Mediciones principales: se pesaron los niños y las mochilas escolares antes de la intervención educativa, inmediatamente después y a los 3 meses de la intervención educativa. Resultados Respecto de la variable «peso excesivo en la mochila», observamos que los niños que recibieron la intervención tienen aproximadamente 3 veces más posibilidades, tanto al terminar dicha intervención como a los 3 meses (RR=2,63 y RR=2,96, respectivamente), de conseguir tener mochilas sin peso excesivo. Respecto de la variable principal del estudio, peso medio de la mochila, la diferencia entre los 2 grupos es superior a 1kg (diferencia señalada como relevante) tanto al acabar la intervención (diferencia de medias (DM)=2,28 kg) como a los 3 meses de la misma (DM=2,24kg), (p=<0,001) en ambos casos. Conclusiones El estudio demuestra que una intervención educativa con revisión del material escolar que transportan los estudiantes de 8 a 10 años consigue una disminución de más de 1 kg del peso de sus mochilas con respecto del grupo control (medias de 2,28kg al finalizar la primera intervención). Además, demuestra que estos resultados se mantienen en el tiempo (media de 2,24kg a los 3 meses) (AU)

Introduction This work shows that classroom educational orientation provided by a physiotherapist can lead to reduction in the weight of backpacks carried by 8-10 year old schoolchildren. The purpose was to have them limit backpack weight to no more than 10-15% of the total weight of the student and avoid some of the spinal cord overload and therefore one of the risk factors of suffering back pain. Higher loads can change spinal curvature with a perception of increased effort and onset of pain. Materials and method Design: randomized, open labeled, controlled clinical trial. Location: public schools in Alcobendas and San Sebastian de los Reyes. Participants: a total of 357 children, aged 8 to 10 years. Main measurements: children and their school backpacks were weighed prior to the educational intervention, immediately after and at three months of the educational intervention. Results Regarding the study primary endpoint, average weight of the backpack, the difference between the two groups was greater than 1kg (difference considered relevant) both at the end of the intervention (difference of means (SD)=2.28kg) and at 3 months of it (SD=2.24kg) (P=<.001). Regarding the endpoint “excess weight in the backpack”, it was observed that those children who received the intervention had approximately three times more likelihood both at the end of said intervention and at 3 months (RR=2.63 and RR=2.96, respectively) of carrying backpacks without excessive weight. Conclusions The study shows educational intervention with review of school supplies transported by students aged 8 to 10 achieves a decrease of more than onekg in weight of their backpacks versus the control group (mean 2.28kg at the end of the first intervention). It also shows that these results are maintained over time (mean 2.24kg at 3 months) (AU)

Parasites of cetaceans stranded on the Pacific coast of Costa Rica.

Information regarding parasitic fauna of cetaceans from Costa Rica is provided for the first time. A total of 25 stranded dolphins and whales were examined between 2001 and 2009, including striped dolphin (Stenella coeruleoalba) (n=19), pantropical spotted dolphin (S. attenuata) (n=2), spinner dolphin (S. longirostris) (n=1), bottlenose dolphin (Tursiops truncatus) (n=1), dwarf sperm whale (Kogia sima) (n=1) and Cuvier's beaked whale (Ziphius cavirostris) (n=1). Pathological findings associated with the parasites are also presented. In the most representative dolphin species, S. coeruleoalba, the prevalence of parasites was 89.5%; moreover, all examined specimens of S. attenuata, S. longirostris, T. truncatus and Z. cavirostris presented parasites. No parasites were recovered from K. sima. Fourteen helminth taxa were identified, including six species of cestodes (Strobilocephalus triangularis, Tetrabothrius forsteri, Trigonocotyle sp., Phyllobothrium delphini, Monorygma grimaldi, Tetraphyllidea gen. sp. plerocercoid), four digeneans (Nasitrema globicephalae, Brachycladium palliatum, B. pacificum and Oschmarinella albamarina) and four nematodes (Anisakis spp., Halocercus lagenorhynchi, Halocercus sp. and Crassicauda anthonyi). A commensal crustacean, Xenobalanus globicipitis, was also identified. All identified parasites representing new geographic records for the Pacific coast of Central America and new host records are presented. Parasitological information is valuable for conservation of cetaceans in Pacific coast of Costa Rica.

Risk factors for immune reconstitution inflammatory syndrome under combination antiretroviral therapy can be aetiology-specific.

In order to discriminate general from aetiology-specific risk factors for immune reconstitution inflammatory syndrome (IRIS), we followed up, during six months, 99 patients with advanced HIV infection commencing antiretroviral therapy (ART) without active opportunistic infections or evident inflammation. IRIS predictors were determined by univariate analysis using clinical data from 76 ART-responding patients either completing follow-up or developing IRIS, and by multivariate analysis of inflammation, disease progression and nutrition status variables. We identified 23 primary IRIS events (30.3%). Univariate predictors for all IRIS events were higher platelet counts and lower CD4/CD8 ratio, whereas subclinical inflammation was the multivariate predictor. Platelets, alkaline phosphatase levels and %CD8 T-cells in univariate analysis also predicted mycobacteria-associated IRIS independently, remaining elevated during follow-up. Herpesvirus IRIS was predicted by platelets and inflammation. Indicators of advanced HIV disease and subclinical inflammation jointly predict IRIS, and some are specific of the underlying microbial aetiology, possibly explaining previous reports.

Pathology of striped dolphins (Stenella coeruleoalba) infected with Brucella ceti.

Seventeen striped dolphins (Stenella coeruleoalba) displaying swimming disorders compatible with neurological syndromes were investigated for Brucella infection. Sixteen dolphins had meningoencephalomyelitis. Serum antibody against Brucella antigen was detected in all 14 animals tested and Brucella ceti was isolated from eight out of nine animals. Brucella antigen was detected in the brain by immunofluorescence, but not by immunohistochemical labelling. By contrast, Brucella antigen was demonstrated by immunohistochemistry in the trophoblast of animals with severe placentitis and in the mitral valve of animals with myocarditis. The microscopical lesions observed in the tissues of the infected dolphins were similar to those of chronic brucellosis in man. The severity of brucellosis in S. coeruleoalba indicates that this dolphin species is highly susceptible to infection by B. ceti.

Later onset of herpes zoster-associated immune reconstitution inflammatory syndrome.

OBJECTIVES: The aim of the study was to determine whether immune reconstitution inflammatory syndrome (IRIS) associated with herpes zoster occurs on a different time frame from other instances of IRIS. METHODS: Statistical analysis of onset times of herpes zoster-associated IRIS and other cases of IRIS was carried out in a retrospective cohort starting antiretroviral therapy at advanced stages of HIV infection. RESULTS: Herpes zoster-associated IRIS was significantly more frequent after the first 3 months of successful highly active antiretroviral therapy (HAART), than other instances of IRIS (IRIS associated with tuberculosis, Mycobacterium avium complex, Kaposi's sarcoma, etc.) which mainly occurred during the first 3 months of treatment. CONCLUSIONS: The characteristic onset time pattern of herpes zoster-associated IRIS, coincident with the second phase of immune recovery under HAART, suggests that the immune recovery events underlying herpes zoster-associated IRIS are different from those underlying other types of IRIS. Our findings may be useful in improving the follow-up of individuals who start HAART at an advanced stage of HIV infection.

Kinetics of insulin secretion from MIN6 pseudoislets after encapsulation in a prototype device of a bioartificial pancreas.

Xenotransplantation of insulin-secreting cells from nonhuman sources is an alternative therapeutic approach to bypass the shortage of human pancreatic islet tissue for transplantation in order to treat insulin deficiency in type 1 diabetes mellitus. Therefore, we studied the suitability of pseudoislets generated from insulin-secreting MIN6 tissue culture cells to serve as a surrogate for replacement of pancreatic islets after encapsulation in a minicell, representing a prototype of a new bioartificial pancreas device. MIN6 pseudoislets showed an excellent insulin secretory responsiveness with a typical biphasic secretory pattern to glucose stimulation. When encapsulated in the minicell, insulin release from the pseudoislets in response to glucose stimulation was reduced. The initial first phase insulin secretory response was greatly attenuated. In contrast, the first phase insulin secretory response of the encapsulated pseudoislets was restored on stimulation with the sulfonylurea drug tolbutamide. Our results indicate that the reason for the attenuated first phase of release is the restricted permeability of the pores in the separating membrane in the minicell for the hydrophilic glucose molecule rather than a limited permeability for the secretion product insulin. The reduced release of insulin from the encapsulated pseudoislets could be compensated by overexpression of glucokinase in MIN6 cells, which resulted in an increased glucose responsiveness of the pseudoislets for stimulation with glucose. Thus, this minicell is a well-suited miniature test system for the evaluation of the feasibility of encapsulation of insulin-secreting cells and allows the testing of permeability properties of separating membranes in bioartificial pancreas devices.

[Monitoring of sedation]. / Monitorización de la sedación.

Once analgesia is assured, sedation has special relevance in the critically ill ventilated patient's global treatment. Sedatives should be adjusted to individual needs, by administering minimal effective doses to achieve the AIM. This aim must be clearly identified, defined at the beginning of the treatment and revised on a regular basis, ideally at least once per shift. Sedation strategies should foresee the different needs throughout the day within dynamic sedation concept framework. Required sedation depth depends on the patient's psychological characteristics, foreseen evolution and patient tolerance to the support techniques used in treatment. Sedation monitoring permits identification and correction of under- or over-sedation, either of which could negatively influence critically ill patient evolution. The over-sedation concept must be applied to all situations where patients receive more sedation than required. This Spanish Society of Critical Care Medicine's Analgesia and Sedation Work Group recommends the Richmond Agitation Sedation Scale, due to its interrelationship with the Confusion Assessment Method Scale (CAM-ICU), for sedation monitoring in patients under light sedation while it recommends bispectral index sedation monitoring in patients under deep sedation. In the latter case, maintaining values under 40 on the bispectral index doesn't produce any benefits except in patients who require a maximum decrease in neuronal metabolism. To avoid recall phenomena, bispectral monitoring is highly advisable in patients treated with neuromuscular blockers.

Monitorización de la sedación / Monitoring of sedation

Una vez asegurada la analgesia, la sedación adquiere especial relevancia en el tratamiento integral del paciente crítico ventilado. Los sedantes se deben ajustar a las necesidades individuales del paciente, administrando la mínima dosis necesaria para conseguir el objetivo. Este objetivo debe ser claramente identificado, definido al inicio de la terapéutica y revisado de forma regular, idealmente al menos una vez por turno. La estrategia de sedación debe prever las distintas necesidades a lo largo del día, enmarcándose dentro del contexto de la denominada sedación dinámica. La profundidad de sedación necesaria dependerá de las características psicológicas del paciente, de la naturaleza y gravedad de su situación clínica, de la evolución prevista y de su tolerancia a las técnicas de soporte usadas para el tratamiento. La monitorización de la sedación permite identificar y corregir situaciones de infra o sobresedación que pueden influir negativamente en la evolución de los pacientes críticos. El concepto de sobresedación deberá aplicarse a toda aquella situación en la que al paciente se le administre más sedación de la que realmente necesite. La Richmond agitation sedation scale, por su conexión con el Confusion Assessment Method para la Unidad de Cuidados Intensivos (CAM-ICU), es la recomendada por el Grupo de Trabajo para la monitorización de los pacientes con necesidades de sedación no profunda y la monitorización con el análisis biespectral (BIS®) en los que necesitan sedación profunda. En este caso, valores inferiores de 40 en el BIS® no aportan beneficios, salvo en aquellos pacientes en los que se requiera disminuir al máximo el metabolismo neuronal. La monitorización con BIS® es muy recomendable en los pacientes tratados con bloqueo neuromuscular para impedir los fenómenos de recall (AU)

Once analgesia is assured, sedation has special relevance in the critically ill ventilated patient’s global treatment. Sedatives should be adjusted to individual needs, by administering minimal effective doses to achieve the aim. This aim must be clearly identified, defined at the beginning of the treatment and revised on a regular basis, ideally at least once per shift. Sedation strategies should foresee the different needs throughout the day within dynamic sedation concept framework. Required sedation depth de- pends on the patient’s psychological characteristics, foreseen evolution and patient tolerance to the support techniques used in treatment. Sedation monitoring permits identification and correction of under- or over-sedation, either of which could negatively influence critically ill patient evolution. The over-sedation concept must be applied to all situations where patients receive more sedation than required. This Spanish Society of Critical Care Medicine’s Analgesia and Sedation Work Group recommends the Richmond Agitation Sedation Scale, due to its interrelationship with the Confusion Assessment Method Scale (CAM-ICU), for sedation monitoring in patients under light sedation while it recommends bispectral index sedation monitoring in patients under deep sedation. In the latter case, maintaining values under 40 on the bispectral index doesn’t produce any benefits except in patients who re- quire a maximum decrease in neuronal metabolism. To avoid recall phenomena, bispectral monitoring is highly advisable in patients treated with neuromuscular blockers (AU)

Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus.

The intra-hippocampal administration of interleukin-1beta (IL-1beta) as well as the induction of elevated but physiological levels of IL-1beta within the hippocampus interferes with the formation of long-term memory. There is evidence suggesting that the induction of prostaglandin (PG) formation by IL-1beta is involved in impairments in working and spatial memory following IL-1beta. The present experiments extend these findings by showing that PGs are responsible for memory deficits in contextual fear conditioning that occur following IL-1beta injection into the dorsal hippocampus of Sprague-Dawley rats. Cyclooxygenase (COX) inhibition blocked the disruption in contextual fear conditioning produced by IL-1beta and COX inhibition alone also disrupted contextual memory, suggesting an inverted U-shaped relationship between PG levels and memory. In addition to demonstrating the necessity of PGs in IL-1beta-mediated memory deficits, we also show that PGs injected directly into the dorsal hippocampus are sufficient to impair context memory and significantly reduce post-conditioning levels of BDNF within the hippocampus, suggesting a possible mechanism for the memory-impairing effects of PGs.