High dimensional profiling identifies specific immune types along the recovery trajectories of critically ill COVID19 patients.

The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.

Water associated with residential areas and tourist resorts is the key predictor of Asian tiger mosquito presence on a Mediterranean island.

The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae), is a highly invasive species and a vector of several viruses of serious concern to public health. Investigating the habitat selection of this species at small to medium scales is essential to the planning of effective prevention and control campaigns. The present group considered detailed data for this species' presence/absence collected at 228 sites on Mallorca Island (Spain) in autumn 2015, 3 years after the first detection of the species on the island. Site occupancy models accounting for false negative detections and imperfect monitoring were used to evaluate the relationships between mosquito presence and habitat variables. In the study area, mosquito presence was negatively associated with altitude, probably as a result of greater human presence at low altitudes near the coast. Moreover, the presence of Ae. albopictus was positively associated with swimming pools as a result of associated gardens, plants and sources of fresh water. These two variables were combined to predict the presence of the species across the entire island.

Las reacciones alérgicas frente a las tintas de los tatuajes, un nuevo reto diagnóstico / Allergic Reactions to Tattoo Inks: A New Diagnostic Challenge

No disponible

Angiogenic growth factors in maternal and fetal serum in pregnancies complicated with intrauterine growth restriction.

The aim of this paper was to study if soluble fms-like tyrosine kinase 1 (sFlt-1), free vascular endothelial growth factor (f-VEGF) and the f-VEGF/sFlt-1 quotient in singleton pregnancies complicated with intrauterine growth restriction (IUGR) are different from controls. This was a case-control study between 18 pregnancies with IUGR and 24 controls. Angiogenic growth factors were measured in maternal serum during pregnancy and in umbilical artery and vein at birth. Results showed that maternal plasma f-VEGF and s-Flt-1 were significantly higher in IUGR compared with controls (p = 0.01 and 0.001, respectively). f-VEGF/sFlt-1 quotient was significantly lower in the IUGR group compared with controls. When we analysed umbilical cord angiogenic factors, we found no significant differences in the artery or vein angiogenic growth factors between the IUGR group and controls. It was concluded that mothers of IUGR fetuses have a more anti-angiogenic environment compared to those of controls.

Collection of Culicoides spp. with four light trap models during different seasons in the Balearic Islands.

Bluetongue (BT) is a viral disease that affects ruminants, being especially pathogenic in certain breeds of sheep. Its viral agent (bluetongue virus; BTV) is transmitted by several species of Culicoides biting midges (Diptera: Ceratopogonidae). Different models of suction light traps are being used in a number of countries for the collection of BTV vector species. To determine the relative effectiveness of different light traps under field conditions, four traps (Onderstepoort, Mini-CDC, Rieb and Pirbright) were compared. These traps were rotated between four sites on a cattle farm in Mallorca (Balearic Islands, Spain) for several non-consecutive nights. Results showed remarkable disparities in the efficacy of the traps for the collection of Culicoides midges. The highest number of midges collected in the Onderstepoort trap (x¯±SD=62±94.2) was not significantly different from that collected in the Mini-CDC (x¯±SD=58±139.2). The Rieb trap collected the lowest number of midges (x¯±SD=3±4.0). Significantly higher mean numbers of midges were collected in the Onderstepoort than in either the Pirbright (P=0.002) or Rieb traps (P=0.008). There were also differences in the Culicoides species composition as determine with the various traps. These results indicate that the Onderstepoort or Mini-CDC traps will be more effective than either the Rieb or Pirbright traps for the collection of large numbers of Culicoides midges.

Protection of livestock against bluetongue virus vector Culicoides imicola using insecticide-treated netting in open areas.

The protection of livestock against Culicoides species (Diptera: Ceratopogonidae) using physical barriers or chemically treated barriers is difficult owing to the small size of these biting midges and animal welfare concerns associated with the reduction of air flow. Culicoides imicola Kieffer is the main bluetongue virus vector in the Mediterranean basin, including the southern Iberian peninsula, where livestock is mainly housed in open pens or sheds which offer no physical protection against C. imicola. In this study we assessed the efficacy of surrounding yearling ewe pens with a canvas barrier or a cypermethrin-treated canvas barrier in reducing the entry of Culicoides spp. and C. imicola. Analyses were based on comparisons of Culicoides catches in traps in pens with and without barriers, and in traps located outside pens. Although there was no clear reduction in the abundance of Culicoides other than C. imicola in pens with either barrier, the C. imicola presence was markedly reduced by the insecticide-treated barrier compared with the untreated barrier; the latter did not reduce the abundance of this species in pens. Estimates of the protection conferred against C. imicola by the treated barrier differed depending on whether catch comparisons were based on outside traps or on traps located inside no-barrier pens. The results suggest that the use of insecticide-treated barriers may reduce contact between livestock and C. imicola in open areas or sheds. More research is necessary to assess the degree of protection as a function of barrier height, C. imicola abundance, and the size of the area to be protected.

Variations in the mitochondrial cytochrome c oxidase subunit I gene indicate northward expanding populations of Culicoides imicola in Spain.

Culicoides imicola is the main vector for bluetongue (BT) and African horse sickness (AHS) viruses in the Mediterranean basin and in southern Europe. In this study, we analysed partial mitochondrial cytochrome c oxidase subunit I (COI) gene to characterize and confirm population expansion of Culicoides imicola across Spain. The data were analysed at two hierarchical levels to test the relationship between C. imicola haplotypes in Spain (n = 215 from 58 different locations) and worldwide (n = 277). We found nineteen different haplotypes within the Spanish population, including 11 new haplotypes. No matrilineal subdivision was found within the Spanish population, while western and eastern Mediterranean C. imicola populations were very structured. These findings were further supported by median networks and mismatch haplotype distributions. Median networks demonstrated that the haplotypes we observed in the western Mediterranean region were closely related with one another, creating a clear star-like phylogeny separated only by a single mutation from eastern haplotypes. The two, genetically distinct, sources of C. imicola in the Mediterranean basin, thus, were confirmed. This type of star-like population structure centred around the most frequent haplotype is best explained by rapid expansion. Furthermore, the proposed northern expansion was also supported by the statistically negative Tajima's D and Fu's Fs values, as well as predicted mismatch distributions of sudden and spatially expanding populations. Our results thus indicated that C. imicola population expansion was a rapid and recent phenomenon.

Entry of bluetongue vector Culicoides imicola into livestock premises in Spain.

Culicoides imicola Kieffer is considered to be the main vector of bluetongue disease (BT) and African horse sickness (AHS) in the Mediterranean basin. It has been assumed that this midge species is exophilic and, consequently, that stabling of livestock should provide effective protection against these diseases. This study presents the results of sampling surveys for C. imicola carried out both inside and outside stables on three farms in mainland Spain. The number of C. imicola captured varied as a function of the populations sampled and trap location (inside vs. outside). The daily mean number captured inside during the sampling of each farm population was directly correlated with the daily mean number captured outside, but daily correlation of captures was not observed. By contrast with previous studies, the mean catch of C. imicola inside was consistently higher than that outside. No clear effect of stable characteristics on the degree of entry was detected. In addition, proportions of males and age-graded female groups varied among populations and with trap location. Proportionately more males and fewer engorged females were captured outside than inside, although the proportions varied among stables. These results contrast with those of previous studies, and with the assumed pronounced exophilic behaviour of C. imicola, and raise important questions about the vector activity of this species in the study area and its implications for the epidemiology of BT and/or AHS.

Ecological correlates of bluetongue virus in Spain: predicted spatial occurrence and its relationship with the observed abundance of the potential Culicoides spp. vector.

Using data from bluetongue (BT) outbreaks caused by viral serotype 4 (BTV-4) in Spain during 2004-2005, a predictive model for BTV-4 occurrence in peninsular Spain was developed. An autologistic regression model was employed to estimate the relationships between BTV-4 presence and bioclimatic-related and host-availability-related variables. In addition, the observed abundances of the main potential Culicoides vectors during 2004-2005, namely Culicoides imicola, Culicoides obsoletus group, and species of the Culicoides pulicaris group, were compared between BTV-4 presence/absence areas predicted by the model. BTV-4 occurrence was mainly explained by bioclimatic variables, although a consideration of host-availability variables led to improved fit of the model. The area of BTV-4 presence predicted by the model largely resembled the core distribution area of C. imicola, and this species was the most abundant Culicoides spp. in predicted BTV-4 presence areas. The results suggest that the spatial expansion of BTV-4 took place only as far as those areas in which C. imicola populations efficiently transmitted the virus.

Modelling the distributions and spatial coincidence of bluetongue vectors Culicoides imicola and the Culicoides obsoletus group throughout the Iberian peninsula.

Data obtained by a Spanish national surveillance programme in 2005 were used to develop climatic models for predictions of the distribution of the bluetongue virus (BTV) vectors Culicoides imicola Kieffer (Diptera: Ceratopogonidae) and the Culicoides obsoletus group Meigen throughout the Iberian peninsula. Models were generated using logistic regression to predict the probability of species occurrence at an 8-km spatial resolution. Predictor variables included the annual mean values and seasonalities of a remotely sensed normalized difference vegetation index (NDVI), a sun index, interpolated precipitation and temperature. Using an information-theoretic paradigm based on Akaike's criterion, a set of best models accounting for 95% of model selection certainty were selected and used to generate an average predictive model for each vector. The predictive performances (i.e. the discrimination capacity and calibration) of the average models were evaluated by both internal and external validation. External validation was achieved by comparing average model predictions with surveillance programme data obtained in 2004 and 2006. The discriminatory capacity of both models was found to be reasonably high. The estimated areas under the receiver operating characteristic (ROC) curve (AUC) were 0.78 and 0.70 for the C. imicola and C. obsoletus group models, respectively, in external validation, and 0.81 and 0.75, respectively, in internal validation. The predictions of both models were in close agreement with the observed distribution patterns of both vectors. Both models, however, showed a systematic bias in their predicted probability of occurrence: observed occurrence was systematically overestimated for C. imicola and underestimated for the C. obsoletus group. Average models were used to determine the areas of spatial coincidence of the two vectors. Although their spatial distributions were highly complementary, areas of spatial coincidence were identified, mainly in Portugal and in the southwest of peninsular Spain. In a hypothetical scenario in which both Culicoides members had similar vectorial capacity for a BTV strain, these areas should be considered of special epidemiological concern because any epizootic event could be intensified by consecutive vector activity developed for both species during the year; consequently, the probability of BTV spreading to remaining areas occupied by both vectors might also be higher.

La Unidad de Cirugía sin Ingreso: la gestión basada en procesos / No disponible

En septiembre de 2006 se puso en funcionamiento en nuestro centro una nueva área de atención quirúrgica, integrada en el propio complejo hospitalario. Es una nueva estructuración de los espacios quirúrgicos que forma parte de la estrategia de la organización en su tarea de mejora continua en la atención al paciente. Se trata de un área de Cirugía Mayor Ambulatoria denominada Unidad de Cirugía sin Ingreso, y su gestión se ha estructurado en base a la gestión por procesos. Describiremos en este trabajo la metodología empleada para poner en marcha esta unidad y los pasos necesarios para el control de la mejora continua. Creemos que el desarrollo metodológico del subproceso de Unidad de Cirugía sin Ingreso ha sido muy satisfactorio, tanto en cuanto a la metodología aplicada, como por la experiencia del trabajo en equipo (AU)

In September 2006 our center started a new surgical care area, integrated in the hospital premises. As a new structuration of the surgical spaces, it is a part of the organization’s strategy towards continuous improvement in patient care. It is a Major Ambulatory Surgery area known as Outpatient Surgery Unit, and it’s being managed under the methodology of process management. This paper describes the methodology used to set up this unit, and the necessary steps for monitoring continuous improvement. We believe that the methodological development of the Outpatient Surgery Unit subprocess has been very satisfactory, regarding both the applied methodology and the experience of teamwork (AU)

Seasonal abundance of Culicoides imicola and C. obsoletus in the Balearic islands.

An outbreak of bluetongue (BT) was declared on the Balearic islands of Spain in September and October 2000. In 2001 and 2002, an intensive survey was conducted on cattle farms in Majorca and Minorca for the principal vectors in the Mediterranean Basin, Culicoides imicola and C. obsoletus. Adult Culicoides were collected once a week between June 2001 and December 2002 using CDC light traps. The results from 348 light-trap collections revealed that, in addition to other species of the genus Culicoides, both C. imicola and C. obsoletus appear to be well established on both Majorca and Minorca. Furthermore, both species showed a different seasonal abundance pattern: peak adult populations of C. obsoletus occurred in July, while those of C. imicola peaked in October. These findings indicate that the principal vector in the outbreak of BT in the Balearic islands in 2000 was probably C. imicola.

Presence in the Balearic Islands (Spain) of the midges Culicoides imicola and Culicoides obsoletus group.

An outbreak of the livestock viral disease bluetongue (BT) was detected during September and October 2000 in the Balearic Islands, Spain. Due to the lack of information about the species of Culicoides (Diptera: Ceratopogonidae) reported in the affected area, six farms in Majorca, four in Minorca and one in Ibiza were selected to carry out surveillance of Culicoides adults using light traps. Here, for the first time, we report the presence in the Balearic Islands of Culicoides imicola Keiffer, the main vector of BT, and the Culicoides obsoletus Meigen group.

Neuronal nuclear DNA fragmentation in the aged canine brain: apoptosis or nuclear DNA fragility?

Neuronal DNA fragmentation, as revealed with the method of in situ end-labeling of nuclear DNA fragmentation (TUNEL), has been reported in both the canine and human brains in normal ageing, and in some human age-related neurodegenerative diseases. These results have suggested that apoptosis plays an important role in age-related neuronal loss. It is not clear, however, whether the TUNEL method is highly specific for apoptosis, as DNA fragmentation also occurs in the late stages o necrosis. In this study we have examined 27 dogs aged from 8 to 18 years, to investigate the occurrence of nuclear DNA fragmentation. An autolysis index based on current histological criteria was assigned to each animal to evaluate the effects of autolysis on nuclear DNA integrity. Our results have shown that neuronal nuclear DNA fragmentation is frequent in aged dogs, although it is not accompanied by apoptotic morphology. Yet, a positive relation between TUNEL labelling and the degree of tissue autolysis was observed. In contrast, no TUNEL labelling was detected in young control dogs despite autolysis indices being similar to those in aged dogs. Taken together, these results suggest that neuronal nuclear DNA fragmentation is an age-related phenomenon, not due to apoptosis, whenever other factors render neuronal DNA more susceptible to autolytic fragmentation. We confirm the effect of autolysis in a subpopulation of neurons in the aged canine brain, inducing nuclear DNA fragmentation.

Age-related changes in the brain of the dog.

Although many age-related changes have been described in the nervous system of different species, few authors have specifically studied the topic. Knowledge of such changes is essential to veterinary pathologists, who must distinguish the lesions of specific pathologic processes from those arising as a result of normal aging. The brains of 20 old dogs, ranging in age from 8 to 18 years, were compared with those of 10 young dogs using routine staining techniques (hematoxilin and eosin, periodic acid-Schiff), special staining techniques (periodic acid-methenamine silver stain), and immunohistochemical techniques to detect glial fibrillary acid protein, neurofilaments, ubiquitin, and beta-amyloid. Changes affected meninges and choroid plexuses, meningeal and parenchymal vessels, neurons, and glial cells. Of special interest was the presence of polyglucosan bodies, cerebrovascular amyloid deposition, senile plaques, and ubiquitinated bodies. Some of the age-related changes found, particularly lipofuscin, polyglucosan bodies, and beta-amyloid protein deposition, may play a role in the pathogenesis of the canine cognitive dysfunction syndrome. The dog could be used as a natural animal model for the study of normal aging and human neurodegenerative diseases.