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For years, sustainability has been one of the major challenges of tourism policy. In this context, the 2030 Agenda can become an important tool for working towards sustainability in the tourism sector, as it is a comprehensive and cross-cutting agenda, that includes the economic, social and environmental spheres from an indivisible perspective. This article aims to analyze the integration of the 2030 Agenda into Spanish tourism policy. To do so, qualitative methodology is used, through the technique of content analysis of the guiding documents of this sectoral policy in Spain. Three dimensions of analysis are addressed: problems, values and Sustainable Development Goals (SDGs). The results show that, although Spanish tourism policy incorporates some key issues of the 2030 Agenda, it has a greater focus on the economic and environmental dimensions, while the social dimension is incorporated in a more limited way. These findings show that tourism policy has its own interests and logics from which it approaches each of the dimensions of sustainability.

Introduction Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder pain. Currently, exercise is proposed as the first-line treatment for patients suffering from RCRSP. However, adherence to therapeutic exercise programmes can be poor in the long term in a home setting. The aim of this study is to evaluate the effects of adding video animations to a traditional paper-based exercise programme.Methods and analysis A single-centre, randomised, open-labelled clinical trial will be conducted in a hospital in Spain. Adults aged between 18 and 80 years diagnosed with RCRSP who meet the eligibility criteria will be included. Patients (n=132) will be randomised into two groups, with both receiving paper-based exercises, and the experimental group will also be provided with video animations. The participants will receive seven face-to-face physical therapy sessions and will be asked to perform the exercises at home for 6 months. The primary outcome measure will be the Shoulder Pain and Disability Index, measured at baseline, 3 weeks, 3 months (primary analysis) and 6 months. Secondary outcomes will be the patient’s pain intensity during the last week (rest, during movement and at night); expectations of improvement; satisfaction with treatment; impression of improvement; perceived usability, usefulness and satisfaction of multimedia animations; and adherence to exercises. Generalised least squares regression models with an autoregressive-moving average lag one correlation structure will be implemented, with an intention-to-treat analysis.Ethics and dissemination This study has been approved by the ethics committee of Hospital Universitario Fundación Alcorcón (Madrid, Spain), reference number CI18/16. All participants will sign an informed consent. The results will be published in a peer-reviewed scientific journal.Trial registration ClinicalTrials.gov, NCT05770908.

Abstract The B cell response in the germinal centre (GC) reaction requires a unique bioenergetic supply. Although mitochondria are remodelled upon antigen-mediated B cell receptor stimulation, mitochondrial function in B cells is still poorly understood. To gain a better understanding of the role of mitochondria in B cell function, here we generate mice with B cell-specific deficiency in Tfam, a transcription factor necessary for mitochondrial biogenesis. Tfam conditional knock-out (KO) mice display a blockage of the GC reaction and a bias of B cell differentiation towards memory B cells and aged-related B cells, hallmarks of an aged immune response. Unexpectedly, blocked GC reaction in Tfam KO mice is not caused by defects in the bioenergetic supply but is associated with a defect in the remodelling of the lysosomal compartment in B cells. Our results may thus describe a mitochondrial function for lysosome regulation and the downstream antigen presentation in B cells during the GC reaction, the dysruption of which is manifested as an aged immune response.

Cryptococcus neoformans is included in the World Health Organization fungal priority pathogen list, complied to expedite improved research and public-health interventions. The limited number of available antifungal drugs, their associated toxicity, and the emergence of drug-resistant strains make the development of new therapeutic strategies mandatory. Pattern-recognition receptors (PRRs) from the host’s innate immune system constitute a potential source of new antimicrobial agents. CD5 and CD6 are lymphoid members of the ancient scavenger receptor cysteine-rich superfamily (SRCR-SF) which bind pathogen-associated molecular patterns (PAMPs) of fungal and bacterial origin. Evidence supports the concept that such binding maps to 11-mer sequences present in each of their three SRCR extracellular domains. Herein, we have designed synthetic peptides containing tandems of such 11-mer sequences (namely CD5-T and CD6-T) and analyzed their C. neoformans-binding properties in vitro. Our results show both inhibitory effects on fungal growth and an ability to impact capsule formation and titanization, two critical virulence factors of C. neoformans involved in immune evasion. These effects hold promise for CD5-T and CD6-T peptides as single or adjuvant therapeutic agents against cryptococcosis.

ObjectiveEvidence suggests that individuals who had survived to coronavirus disease, 2019 (COVID-19) could develop neuropathic post-COVID pain. This study investigated the association of serological biomarkers and treatments received during hospitalization with development of neuropathic-associated symptoms.MethodsOne hundred and eighty-three (n = 183) previously hospitalized COVID-19 survivors during the first wave of the pandemic were assessed in a face-to-face interview 9.4 months after hospitalization. Nineteen serological biomarkers, hospitalization data, and treatment during hospitalization were obtained from medical records. Neuropathic pain symptoms (Self-Report Leeds Assessment of Neuropathic Scale), sleep quality (Pittsburgh Sleep Quality Index), pain catastrophizing (Pain Catastrophizing Scale) and anxiety/depressive levels (Hospital Anxiety and Depression Scale) were assessed.ResultsThe prevalence of post-COVID pain was 40.9% (n = 75). Fifteen (20%) patients reported neuropathic symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence or not of neuropathic-associated symptoms. Patients with post-COVID pain had the highest neutrophil count, and post hoc analysis revealed that patients with neuropathic post-COVID associated symptoms had lower neutrophil count (p = 0.04) compared with those without neuropathic pain, but differences were small and possible not clinically relevant. No differences in fatigue, dyspnea, brain fog, anxiety or depressive levels, poor sleep, or pain catastrophism between patients with and without neuropathic symptoms were found.ConclusionIt seems that neuropathic-like post-COVID pain symptoms are not associated with neither of assessed serological biomarkers at hospital admission nor hospitalization treatments received in this cohort of hospitalized COVID-19 survivors.

Abstract Background The effect of the cecal microbiome on growth of rabbits that were fed under different regimes has been studied previously. However, the term “effect” carries a causal meaning that can be confounded because of potential genetic associations between the microbiome and production traits. Structural equation models (SEM) can help disentangle such a complex interplay by decomposing the effect on a production trait into direct host genetics effects and indirect host genetic effects that are exerted through microbiota effects. These indirect effects can be estimated via structural coefficients that measure the effect of the microbiota on growth while the effects of the host genetics are kept constant. In this study, we applied the SEM approach to infer causal relationships between the cecal microbiota and growth of rabbits fed under ad libitum (ADGAL) or restricted feeding (ADGR). Results We identified structural coefficients that are statistically different from 0 for 138 of the 946 operational taxonomic units (OTU) analyzed. However, only 15 and 38 of these 138 OTU had an effect greater than 0.2 phenotypic standard deviations (SD) on ADGAL and ADGR, respectively. Many of these OTU had a negative effect on both traits. The largest effects on ADGR were exerted by an OTU that is taxonomically assigned to the Desulfovibrio genus (− 1.929 g/d, CSS-normalized OTU units) and by an OTU that belongs to the Ruminococcaceae family (1.859 g/d, CSS-normalized OTU units). For ADGAL, the largest effect was from OTU that belong to the S24-7 family (− 1.907 g/d, CSS-normalized OTU units). In general, OTU that had a substantial effect had low to moderate estimates of heritability. Conclusions Disentangling how direct and indirect effects act on production traits is relevant to fully describe the processes of mediation but also to understand how these traits change before considering the application of an external intervention aimed at changing a given microbial composition by blocking/promoting the presence of a particular microorganism.

IntroductionAntimicrobial resistance is a pressing global concern that has led to the search for new antibacterial agents with novel targets or non-traditional approaches. Recently, organogold compounds have emerged as a promising class of antibacterial agents. In this study, we present and characterize a (C^S)-cyclometallated Au(III) dithiocarbamate complex as a potential drug candidate.Methods and resultsThe Au(III) complex was found to be stable in the presence of effective biological reductants, and showed potent antibacterial and antibiofilm activity against a wide range of multidrug-resistant strains, particularly gram-positive strains, and gram-negative strains when used in combination with a permeabilizing antibiotic. No resistant mutants were detected after exposing bacterial cultures to strong selective pressure, indicating that the complex may have a low propensity for resistance development. Mechanistic studies indicate that the Au(III) complex exerts its antibacterial activity through a multimodal mechanism of action. Ultrastructural membrane damage and rapid bacterial uptake suggest direct interactions with the bacterial membrane, while transcriptomic analysis identified altered pathways related to energy metabolism and membrane stability including enzymes of the TCA cycle and fatty acid biosynthesis. Enzymatic studies further revealed a strong reversible inhibition of the bacterial thioredoxin reductase. Importantly, the Au(III) complex demonstrated low cytotoxicity at therapeutic concentrations in mammalian cell lines, and showed no acute in vivo toxicity in mice at the doses tested, with no signs of organ toxicity.DiscussionOverall, these findings highlight the potential of the Au(III)-dithiocarbamate scaffold as a basis for developing novel antimicrobial agents, given its potent antibacterial activity, synergy, redox stability, inability to produce resistant mutants, low toxicity to mammalian cells both in vitro and in vivo, and non-conventional mechanism of action.

Abstract Background The rabbit cecum hosts and interacts with a complex microbial ecosystem that contributes to the variation of traits of economic interest. Although the influence of host genetics on microbial diversity and specific microbial taxa has been studied in several species (e.g., humans, pigs, or cattle), it has not been investigated in rabbits. Using a Bayes factor approach, the aim of this study was to dissect the effects of host genetics, litter and cage on 984 microbial traits that are representative of the rabbit microbiota. Results Analysis of 16S rDNA sequences of cecal microbiota from 425 rabbits resulted in the relative abundances of 29 genera, 951 operational taxonomic units (OTU), and four microbial alpha-diversity indices. Each of these microbial traits was adjusted with mixed linear and zero-inflated Poisson (ZIP) models, which all included additive genetic, litter and cage effects, and body weight at weaning and batch as systematic factors. The marginal posterior distributions of the model parameters were estimated using MCMC Bayesian procedures. The deviance information criterion (DIC) was used for model comparison regarding the statistical distribution of the data (normal or ZIP), and the Bayes factor was computed as a measure of the strength of evidence in favor of the host genetics, litter, and cage effects on microbial traits. According to DIC, all microbial traits were better adjusted with the linear model except for the OTU present in less than 10% of the animals, and for 25 of the 43 OTU with a frequency between 10 and 25%. On a global scale, the Bayes factor revealed substantial evidence in favor of the genetic control of the number of observed OTU and Shannon indices. At the taxon-specific level, significant proportions of the OTU and relative abundances of genera were influenced by additive genetic, litter, and cage effects. Several members of the genera Bacteroides and Parabacteroides were strongly influenced by the host genetics and nursing environment, whereas the family S24-7 and the genus Ruminococcus were strongly influenced by cage effects. Conclusions This study demonstrates that host genetics shapes the overall rabbit cecal microbial diversity and that a significant proportion of the taxa is influenced either by host genetics or environmental factors, such as litter and/or cage.

Current evidence suggests that a group of patients who had survived coronavirus disease, 2019 (COVID-19) and developed post-COVID pain can exhibit altered nociceptive processing. The role of serological biomarkers and hospitalization treatments in post-COVID pain is unclear. This study aimed to investigate the association of serological biomarkers and treatments received during hospitalization with sensitization-associated symptoms in COVID-19 survivors with post-COVID pain. One hundred and eighty-three (n = 183) patients who had been hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed in a face-to-face interview 9.4 (SD 3.4) months after hospitalization. Levels of 19 serological biomarkers, hospitalization data, and treatments during hospitalization were obtained from hospital records. Sensitization-associated symptoms (Central Sensitization Inventory, CSI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophism (Pain Catastrophizing Scale), and anxiety/depressive level (Hospital Anxiety and Depression Scale, HADS) were assessed. The prevalence of post-COVID pain was 40.9% (n = 75). Twenty-nine (38.6%) patients had sensitization-associated symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence of sensitization-associated symptoms. The analysis revealed that patients with sensitization-associated symptoms exhibited higher lymphocyte count and lower urea levels than those without sensitization-associated symptoms, but differences were small. Pain catastrophism and depressive levels, but not fatigue, dyspnea, brain fog, anxiety levels, or poor sleep, were higher in individuals with sensitization-associated symptoms. In conclusion, this study revealed that sensitization-associated post-COVID pain symptoms are not associated with serological biomarkers at hospital admission and hospitalization treatments received.

A pesar del éxito creciente de la gamificación en la universidad, resulta sorprendente que todavía no existan estudios sobre esta innovación docente en el campo de las políticas públicas. Este artículo pretende colmar este vacío. Después de recordar los fundamentos del concepto de gamificación, sus beneficios y sus limitaciones, este artículo pone de relieve una serie de actividades desarrolladas previamente: el uso de ladrillos Lego, un concurso de Kahoot, un rally urbano, un juego de supervivencia con huertos, un juego de escape, una competición de SimCity y una simulación basada en Diplomacy. Este artículo debe ser considerado como una hoja de ruta que debe ser adaptada al contexto de cada docente. Se aboga por un uso moderado y razonado de la gamificación. Esta corriente debe ser considerada por lo que es: una simple herramienta al servicio del aprendizaje, y no como un fin en sí misma.

El arsénico (As) es un elemento tóxico presente en el medio ambiente que representa una amenaza para la salud de los consumidores. Para identificar el contenido de arsénico en ríos, páramos y pozos de la ciudad de Cuenca, y en ríos de la ciudad de Azogues, se realizaron dos campañas de monitoreo en el período agosto-noviembre de 2017, durante un período hidrológico de bajo y alto caudal, respectivamente. Las mediciones abarcaron indicadores de calidad fisicoquímica como pH, color, turbidez y conductividad. Los resultados muestran que los páramos y pozos están libres de As, mientras que esta sustancia tóxica está presente en aguas superficiales con niveles más altos en períodos de alto caudal. Se encontró una asociación significativa entre la concentración de As y el pH del agua del río. El riesgo de toxicidad crónica por consumo es casi inexistente porque los niveles de As observados superan solo excepcionalmente el límite permisible establecido por el reglamento ecuatoriano TULSMA (Texto Unificado de Legislación Ambiental Secundaria). La presencia de As en aguas superficiales es el resultado de actividades antropológicas como el uso de pesticidas. Es necesario un monitoreo permanente de la calidad de los recursos hídricos para consumo humano, particularmente en la época de lluvias, debido a los procesos de contaminación difusos y difíciles de controlar.

Summary: CD6 is a lymphocyte-specific scavenger receptor expressed on adaptive (T) and innate (B1a, NK) immune cells, which is involved in both fine-tuning of lymphocyte activation/differentiation and recognition of bacterial-associated molecular patterns (i.e., lipopolysaccharide). However, evidence on CD6’s role in the physiological response to bacterial infection was missing. Our results show that induction of monobacterial and polymicrobial sepsis in Cd6−/− mice results in lower survival rates and increased bacterial loads and pro-inflammatory cytokine levels. Steady state analyses of Cd6−/− mice show decreased levels of natural polyreactive antibodies, concomitant with decreased cell counts of spleen B1a and marginal zone B cells. Adoptive transfer of wild-type B cells and mouse serum, as well as a polyreactive monoclonal antibody improve Cd6−/− mouse survival rates post-sepsis. These findings support a nonredundant role for CD6 in the early response against bacterial infection, through homeostatic expansion and functionality of innate-related immune cells.

External male genitalia have rarely been evaluated on fetal ultrasound. Apart from visualization of the penis for fetal sex determination, there are no specific instructions or recommendations from scientific societies. This study aimed to review the current knowledge about prenatal diagnosis of the scrotum and internal structures, with discussion regarding technical aspects and clinical management. We conducted an article search in Medline, EMBASE, Scopus, Google Scholar, and Web of Science databases for studies in English or Spanish language that discussed prenatal scrotal pathologies. We identified 72 studies that met the inclusion criteria. Relevant data were grouped into sections of embryology, ultrasound, pathology, and prenatal diagnosis. The scrotum and internal structures show a wide range of pathologies, with varying degrees of prevalence and morbidity. Most of the reported cases have described incidental findings diagnosed via striking ultrasound signs. Studies discussing normative data or management are scarce.

Abstract Gut microbiota plays an important role in nutrient absorption and could impact rabbit feed efficiency. This study aims at investigating such impact by evaluating the value added by microbial information for predicting individual growth and cage phenotypes related to feed efficiency. The dataset comprised individual average daily gain and cage-average daily feed intake from 425 meat rabbits, in which cecal microbiota was assessed, and their cage mates. Despite microbiota was not measured in all animals, consideration of pedigree relationships with mixed models allowed the study of cage-average traits. The inclusion of microbial information into certain mixed models increased their predictive ability up to 20% and 46% for cage-average feed efficiency and individual growth traits, respectively. These gains were associated with large microbiability estimates and with reductions in the heritability estimates. However, large microbiabililty estimates were also obtained with certain models but without any improvement in their predictive ability. A large proportion of OTUs seems to be responsible for the prediction improvement in growth and feed efficiency traits, although specific OTUs taxonomically assigned to 5 different phyla have a higher weight. Rabbit growth and feed efficiency are influenced by host cecal microbiota, thus considering microbial information in models improves the prediction of these complex phenotypes.

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD’s clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.

Third trimester ultrasound has long been in obstetrics a topic of debate. This issue is framed in a historical debate on the effectiveness of routine obstetrical ultrasound and two opposing trends originated in America and Europe, respectively. Primary function of this ultrasound has been to detect fetal growth restriction, but no study has shown evidence of improving perinatal outcomes. Other secondary functions are detection of fetal abnormalities or evaluation of fetal presentation, and they have also shown no evidence. Despite the continuous appearance of works in this regard, health policies of both american and european trends have not been modified. Future seems to show a prolongation of the stalemate. Those health systems with a universal third trimester policy should propose an optimization of the test, in order to improve the benefits and obtain data for future studies that could resolve this longstanding debate.

Abstract Background The effect of the production environment and different management practices in rabbit cecal microbiota remains poorly understood. While previous studies have proved the impact of the age or the feed composition, research in the breeding farm and other animal management aspects, such as the presence of antibiotics in the feed or the level of feeding, is still needed. Characterization of microbial diversity and composition of growing rabbits raised under different conditions could help better understand the role these practices play in cecal microbial communities and how it may result in different animal performance. Results Four hundred twenty-five meat rabbits raised in two different facilities, fed under two feeding regimes (ad libitum or restricted) with feed supplemented or free of antibiotics, were selected for this study. A 16S rRNA gene-based assessment through the MiSeq Illumina sequencing platform was performed on cecal samples collected from these individuals at slaughter. Different univariate and multivariate approaches were conducted to unravel the influence of the different factors on microbial alpha diversity and composition at phylum, genus and OTU taxonomic levels. The animals raised in the facility harboring the most stable environmental conditions had greater, and less variable, microbial richness and diversity. Bootstrap univariate analyses of variance and sparse partial least squares-discriminant analyses endorsed that farm conditions exerted an important influence on rabbit microbiota since the relative abundances of many taxa were found differentially represented between both facilities at all taxonomic levels characterized. Furthermore, only five OTUs were needed to achieve a perfect classification of samples according to the facility where animals were raised. The level of feeding and the presence of antibiotics did not modify the global alpha diversity but had an impact on some bacteria relative abundances, albeit in a small number of taxa compared with farm, which is consistent with the lower sample classification power according to these factors achieved using microbial information. Conclusions This study reveals that factors associated with the farm effect and other management factors, such as the presence of antibiotics in the diet or the feeding level, modify cecal microbial communities. It highlights the importance of offering a controlled breeding environment that reduces differences in microbial cecal composition that could be responsible for different animal performance.

Abstract Background An Advanced Care Planning (ACP) program of health decisions is the result of a process of reflection and relationship-building between the patient, their relatives and health professionals. It is based on respect for patients’ autonomy, involving them in making decisions about their disease in a way that is shared between the medical team, the patient and their relatives. Up until now, the efficacy of an ACP has not been measured in the existing literature, and therefore it is unknown if these programs reach their goal. The main objective of our study is to evaluate the efficacy of an ACP program for decision-making in patients with advanced heart failure (HF) in comparison to usual follow up and care. This objective will be evaluated by the Patient Activation Measure test, which measures the participation and self-management of the patient in decision-making. Secondary objectives: to evaluate the effect of the program on quality of life, to know if the patients wishes expressed through the ACP program are fulfilled, to measure the impact of the program on patients’ caregivers, to determine the satisfaction of patients included in the program and to evaluate the effect on quality of death. Methods Randomized multicentre clinical trial at four hospitals in Madrid. Once they are included in the study, patients’ allocation to groups (control vs intervention) will be made by alternative sampling. ACP will be applied to the intervention group, whereas in the Control Group usual follow-up will be carried out in HF units. All patients will fulfil questionnaires and tests related to the objectives of the study again after a 12-month follow-up period in order to gauge the effect of ACP in patients with advanced HF. Discussion The characteristics of patients with advanced HF make them a model for designing ACP programs, given the high prevalence of this disease, the progressive increase in its incidence and it’s clinical characteristics. Until now, the efficacy of this type of program has not been measured, so this Clinical Trial can provide relevant data for future ACP projects. Trial registration ClinicalTrials.gov Identifier: NCT04424680. Registered 9 June 2020. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04424680?term=NCT04424680&draw=2&rank=1 .

The worldwide emergence and spread of infections caused by multidrug-resistant bacteria endangers the efficacy of current antibiotics in the clinical setting. The lack of new antibiotics in the pipeline points to the need of developing new strategies. Recently, gold-based drugs are being repurposed for antibacterial applications. Among them, gold(III) complexes have received increasing attention as metal-based anticancer agents. However, reports on their antibacterial activity are scarce due to stability issues. The present work demonstrates the antibacterial activity of the gold(III) complex 2 stabilized as C∧S-cycloaurated containing a diphenylphosphinothioic amide moiety, showing minimum inhibitory concentration (MIC) values that ranged from 4 to 8 and from 16 to 32 mg/L among Gram-positive and Gram-negative multidrug-resistant (MDR) pathogens, respectively. Complex 2 has a biofilm inhibitory activity of only two to four times than its MIC. We also describe for the first time a potent antibacterial synergistic effect of a gold(III) complex combined with colistin, showing a bactericidal effect in less than 2 h; confirming the role of the outer membrane as a permeability barrier. Complex 2 shows a low rate of internalization in Staphylococcus aureus and Acinetobacter baumannii; it does not interact with replication enzymes or efflux pumps, causes ultrastructural damages in both membrane and cytoplasmic levels, and permeabilizes the bacterial membrane. Unlike control antibiotics, complex 2 did not generate resistant mutants in 30-day sequential cultures. We detected lower cytotoxicity in a non-tumoral THLE-2 cell line (IC50 = 25.5 μM) and no acute toxicity signs in vivo after an i.v. 1-mg/kg dose. The characterization presented here reassures the potential of complex 2 as a new chemical class of antimicrobial agents.

Encapsulation of water-soluble bioactive compounds for enabling specific accumulation in tumor locations, while avoiding premature clearance and/or degradation in the bloodstream, is one of the main hallmarks in nanomedicine, especially that of NIR fluorescent probes for cancer theragnosis. The herein reported technology furnishes water-dispersible double-walled polyurethane-polyurea hybrid nanocapsules (NCs) loaded with indocyanine green (ICG-NCs), using a versatile and highly efficient one-pot and industrially scalable synthetic process based on the use of two different prepolymers to set up the NCs walls. Flow cytometry and confocal microscopy confirmed that both ICG-loaded NCs internalized in monocyte-derived dendritic cells (moDCs). The in vivo analysis of xenograft A375 mouse melanoma model revealed that amphoteric functionalization of NCs’ surface promotes the selective accumulation of ICG-NCs in tumor tissues, making them promising agents for a less-invasive theragnosis of cancer.

Frontotemporal dementia (FTD) is a highly heritable condition. Up to 40% of FTD is familial and an estimated 15% to 40% is due to single-gene mutations. It has been estimated that the G4C2 hexanucleotide repeat expansions in the C9ORF72 gene can explain up to 37.5% of the familial cases of FTD, especially in populations of Caucasian origin. The purpose of this paper is to evaluate hereditary risk across the clinical phenotypes of FTD and the frequency of the G4C2 expansion in a Colombian cohort diagnosed with FTD.Methods: A total of 132 FTD patients were diagnosed according to established criteria in the behavioral variant FTD, logopenic variant PPA, non-fluent agrammatic PPA, and semantic variant PPA. Hereditary risk across the clinical phenotypes was established in four categories that indicate the pathogenic relationship of the mutation: high, medium, low, and apparently sporadic, based on those proposed by Wood and collaborators. All subjects were also examined for C9ORF72 hexanucleotide expansion (defined as >30 repetitions).Results: There were no significant differences in the demographic characteristics of the patients between the clinical phenotypes of FTD. The higher rate phenotype was bvFTD (62.12%). In accordance with the risk classification, we found that 72 (54.4%) complied with the criteria for the sporadic cases; for the familial cases, 23 (17.4%) fulfilled the high-risk criteria, 23 (17.4%) fulfilled the low risk criteria, and 14 (10.6%) fulfilled the criteria to be classified as subject to medium risk. C9ORF72 expansion frequency was 0.76% (1/132).Conclusion: The FTD heritability presented in this research was very similar to the results reported in the literature. The C9ORF72 expansion frequency was low. Colombia is a triethnic country, with a high frequency of genetic Amerindian markers; this shows consistency with the present results of a low repetition frequency. This study provides an initial report of the frequency for the hexanucleotide repeat expansions in C9ORF72 in patients with FTD in a Colombian population and paves the way for further study of the possible genetic causes of FTD in Colombia.

Abstract Background The importance of submicroscopic malaria infections in high-transmission areas could contribute to maintain the parasite cycle. Regarding non-endemic areas, its importance remains barely understood because parasitaemia in these afebrile patients is usually below the detection limits for microscopy, hence molecular techniques are often needed for its diagnosis. In addition to this, the lack of standardized protocols for the screening of submicroscopic malaria in immigrants from endemic areas may underestimate the infection with Plasmodium spp. The aim of this study was to assess the prevalence of submicroscopic malaria in afebrile immigrants living in a non-endemic area. Methods A prospective, observational, multicentre study was conducted. Afebrile immigrants were included, microscopic observation of Giemsa-stained thin and thick blood smears, and two different molecular techniques detecting Plasmodium spp. were performed. Patients with submicroscopic malaria were defined as patients with negative blood smears and detection of DNA of Plasmodium spp. with one or both molecular techniques. Demographic, clinical, analytical and microbiological features were recorded and univariate analysis by subgroups was carried out with STATA v15. Results A total of 244 afebrile immigrants were included in the study. Of them, 14 had a submicroscopic malaria infection, yielding a prevalence of 5.7% (95% confidence interval 3.45–9.40). In 71.4% of the positive PCR/negative microscopy cases, Plasmodium falciparum alone was the main detected species (10 out of the 14 patients) and in 4 cases (28.6%) Plasmodium vivax or Plasmodium ovale were detected. One patient had a mixed infection including three different species. Conclusions The prevalence of submicroscopic malaria in afebrile immigrants was similar to that previously described in Spain. Plasmodium vivax and P. ovale were detected in almost a third of the submicroscopic infections. Screening protocols for afebrile immigrants with molecular techniques could be useful for a proper management of these patients.

Abstract Background To date, the molecular mechanisms that underlie residual feed intake (RFI) in pigs are unknown. Results from different genome-wide association studies and gene expression analyses are not always consistent. The aim of this research was to use machine learning to identify genes associated with feed efficiency (FE) using transcriptomic (RNA-Seq) data from pigs that are phenotypically extreme for RFI. Methods RFI was computed by considering within-sex regression on mean metabolic body weight, average daily gain, and average backfat gain. RNA-Seq analyses were performed on liver and duodenum tissue from 32 high and 33 low RFI pigs collected at 153 d of age. Machine-learning algorithms were used to predict RFI class based on gene expression levels in liver and duodenum after adjusting for batch effects. Genes were ranked according to their contribution to the classification using the permutation accuracy importance score in an unbiased random forest (RF) algorithm based on conditional inference. Support vector machine, RF, elastic net (ENET) and nearest shrunken centroid algorithms were tested using different subsets of the top rank genes. Nested resampling for hyperparameter tuning was implemented with tenfold cross-validation in the outer and inner loops. Results The best classification was obtained with ENET using the expression of 200 genes in liver [area under the receiver operating characteristic curve (AUROC): 0.85; accuracy: 0.78] and 100 genes in duodenum (AUROC: 0.76; accuracy: 0.69). Canonical pathways and candidate genes that were previously reported as associated with FE in several species were identified. The most remarkable pathways and genes identified were NRF2-mediated oxidative stress response and aldosterone signalling in epithelial cells, the DNAJC6, DNAJC1, MAPK8, PRKD3 genes in duodenum, and melatonin degradation II, PPARα/RXRα activation, and GPCR-mediated nutrient sensing in enteroendocrine cells and SMOX, IL4I1, PRKAR2B, CLOCK and CCK genes in liver. Conclusions ML algorithms and RNA-Seq expression data were found to provide good performance for classifying pigs into high or low RFI groups. Classification was better with gene expression data from liver than from duodenum. Genes associated with FE in liver and duodenum tissue that can be used as predictive biomarkers for this trait were identified.

La tecnología de energía solar, fuente de energía natural y gratuita, es implementada en lugares con acceso limitado a la energía eléctrica tradicional, en algunos casos en el ámbito agrícola o en pequeños asentamientos humanos rurales. Actualmente, los sistemas comerciales, incluyen una unidad de control de carga con una pequeña pantalla, con la finalidad de mostrar el voltaje generado, pero desafortunadamente el operario debe de acudir hasta el controlador para revisar su desempeño, por lo que es necesario tener una herramienta que permita conocer la conversión energética en tiempo real de manera remota. Esto se puede lograr haciendo uso de la tecnología del internet de las cosas (IoT). En la actualidad existen diversas plataformas IoT; algunas son gratuitas, otras son versiones demostrativas o de paga. Método: En el presente trabajo se desarrolló un prototipo con un sistema de monitoreo de voltaje e intensidad luminosa de una pequeña celda solar y un sensor digital TSL2561. Se utilizó el entorno de programación de Arduino acoplado a una plataforma (IoT) myDevices Cayenne para poder transmitir y acceder a los datos de manera remota. Resultados: Con la integración de los componentes se logró monitorear en la plataforma myDevices Cayenne en tiempo real el voltaje de la celda solar y la intensidad luminosa del entorno de una manera visual e intuitiva, desde cualquier computadora o teléfono celular con acceso a internet. Discusión: La plataforma de IoT myDevices Cayenne se convierte en una opción atractiva, accesible, robusta y fácil de usar en el desarrollo de proyectos novedosos con IoT aplicados a diferentes sectores de importancia económica.

B-cell lymphomas are one of the most biologically and molecularly heterogeneous group of malignancies. The inherent complexity of this cancer subtype necessitates the development of appropriate animal model systems to characterize the disease with the ultimate objective of identifying effective therapies. In this article, we discuss a new driver of B-cell lymphomas – hnRNP K (heterogenous nuclear ribonucleoprotein K)—an RNA-binding protein. We introduce the Eµ-Hnrnpk mouse model, a murine model characterized by hnRNP K overexpression in B cells, which develops B-cell lymphomas with high penetrance. Molecular analysis of the disease developed in this model reveals an upregulation of the c-Myc oncogene via post-transcriptional and translational mechanisms underscoring the impact of non-genomic MYC activation in B-cell lymphomas. Finally, the transplantability of the disease developed in Eµ-Hnrnpk mice makes it a valuable pre-clinical platform for the assessment of novel therapeutics.

BackgroundThe differential diagnosis of glioblastomas (GBM) from solitary brain metastases (SBM) is essential because the surgical strategy varies according to the histopathological diagnosis. Intraoperative ultrasound elastography (IOUS-E) is a relatively novel technique implemented in the surgical management of brain tumors that provides additional information about the elasticity of tissues. This study compares the discriminative capacity of intraoperative ultrasound B-mode and strain elastography to differentiate GBM from SBM.MethodsWe performed a retrospective analysis of patients who underwent craniotomy between March 2018 to June 2020 with glioblastoma (GBM) and solitary brain metastases (SBM) diagnoses. Cases with an intraoperative ultrasound study were included. Images were acquired before dural opening, first in B-mode, and then using the strain elastography module. After image pre-processing, an analysis based on deep learning was conducted using the open-source software Orange. We have trained an existing neural network to classify tumors into GBM and SBM via the transfer learning method using Inception V3. Then, logistic regression (LR) with LASSO (least absolute shrinkage and selection operator) regularization, support vector machine (SVM), random forest (RF), neural network (NN), and k-nearest neighbor (kNN) were used as classification algorithms. After the models’ training, ten-fold stratified cross-validation was performed. The models were evaluated using the area under the curve (AUC), classification accuracy, and precision.ResultsA total of 36 patients were included in the analysis, 26 GBM and 10 SBM. Models were built using a total of 812 ultrasound images, 435 of B-mode, 265 (60.92%) corresponded to GBM and 170 (39.8%) to metastases. In addition, 377 elastograms, 232 (61.54%) GBM and 145 (38.46%) metastases were analyzed. For B-mode, AUC and accuracy values of the classification algorithms ranged from 0.790 to 0.943 and from 72 to 89%, respectively. For elastography, AUC and accuracy values ranged from 0.847 to 0.985 and from 79% to 95%, respectively.ConclusionAutomated processing of ultrasound images through deep learning can generate high-precision classification algorithms that differentiate glioblastomas from metastases using intraoperative ultrasound. The best performance regarding AUC was achieved by the elastography-based model supporting the additional diagnostic value that this technique provides.

Background CD6 is a lymphocyte surface co-receptor physically associated with the T-cell receptor (TCR)/CD3 complex at the center of the immunological synapse. There, CD6 assists in cell-to-cell contact stabilization and modulation of activation/differentiation events through interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), its main reported ligand. While accumulating evidence is attracting new interest on targeting CD6 for therapeutic purposes in autoimmune disorders, little is known on its potential in cancer. In an attempt to elucidate the in vivo relevance of blocking CD6-mediated interactions in health and disease, we explored the consequences of expressing high circulating levels of a soluble form CD6 (sCD6) as a decoy receptor.Methods High sCD6 serum levels were achieved by using transgenic C57BL/6 mice expressing human sCD6 under the control of lymphoid-specific transcriptional elements (shCD6LckEμTg) or wild type either transduced with hepatotropic adeno-associated virus coding for mouse sCD6 or undergoing repeated infusions of recombinant human sCD6 protein. Characterization of sCD6-induced changes was performed by ex vivo flow cytometry and functional analyses of mouse lymphoid organ cells. The in vivo relevance of those changes was explored by challenging mice with subcutaneous or metastatic tumors induced by syngeneic cancer cells of different lineage origins.Results Through a combination of in vitro and in vivo studies, we show that circulating sCD6 expression induces defective regulatory T cell (Treg) generation and function, decreased CD166/ALCAM-mediated tumor cell proliferation/migration and impaired galectin-induced T-cell apoptosis, supporting the fact that sCD6 modulates antitumor lymphocyte effector function and tumorigenesis. Accordingly, sCD6 expression in vivo resulted in delayed subcutaneous tumor growth and/or reduced metastasis on challenge of mice with syngeneic cancer cells.Conclusions Evidence is provided for the disruption of CD6 receptor–ligand interactions as a feasible immunomodulatory approach in cancer.

Abstract Background Malaria is currently the most important human parasitic disease in the world responsible for high morbidity and mortality. Appropriate diagnostic methods are essential for early detection. Microscopy examination remains the gold standard, although molecular techniques have higher sensitivity and are very useful in cases of low parasitaemia and mixed infections. The objective of this study was to evaluate a new commercial molecular diagnostic technique. Methods A prospective, observational, multicentre study was performed between January 2015 and April 2017. All participants were immigrants from malaria-endemic areas, who were divided into two groups: asymptomatic group and symptomatic. Samples from both groups were evaluated by a rapid diagnostic test (ImmunoQuick® Malaria + 4 RDT), microscopy examination, and two commercial molecular malaria tests (FTD Malaria and FTD Malaria Differentiation), then compared against an in-house reference PCR technique. Results In all, 250 patients were included: 164 (65.6%) in the asymptomatic group, and 86 (34.4%) in the symptomatic group. There were seven cases of asymptomatic parasitaemia (prevalence = 2.8%) that were detected only by molecular methods. In the symptomatic group, there were seven cases of submicroscopic malaria. The main species detected was Plasmodium falciparum (96.6%). The commercial molecular technique had higher sensitivity than the other methods (S = 96%) and a high rate of concordance with the in-house reference PCR technique (Kappa score = 0.93). Conclusions The molecular techniques, although slower than microscopy, have adequate diagnostic accuracy and are very useful for the detection of P. falciparum in cases with low parasitaemia.

This article forms part of a classic social science debate on the role of the media in the construction of social and political narratives. The object of the paper is to study the rise and fall of the concept of tourismphobia in the Spanish media. The case is analyzed in the light of public policies studies, especially those analyzing agenda-setting, the social construction of the definition of public problems and the struggles of coalitions seeking to impose their public policy narratives in the policy-making process. With this purpose, a database was used that collected more than 11,000 news items over a substantial period of time. Its analysis reveals that media attention rises sharply after active protest actions against tourist saturation and that the term is mostly linked to specific territories and cities and to certain political figures. It also allows us to observe how some political responses to the problem appear more in the media, while others are minimized. The conclusions indicate that the “tourismphobia” neologism was capitalized on – which is often the case with terms that circulate in the public sphere – by various groups attempting to highlight some of its semantic dimensions over others. The study also reveals that the media assume an active position in the construction of discourses in relation to tourism also as a political and not just an economic issue. Furthermore, it shows that the use of the term has greatly declined, either because the problem has become dormant or because it has been reformulated into other terms that are more in line with dominant narratives.

En los últimos años, se extiende la idea de que el turismo podría estar generando profundas contradicciones en algunas ciudades y que esto exigiría una política turística más madura y compleja. El objetivo del presente trabajo es ilustrar como, en algunas ocasiones, las decisiones que se adoptan por el gobierno de una ciudad pueden explicarse mejor con modelos que dibujan un proceso anárquico, pero altamente organizado (Cohen et al., 1972 y 2011), en donde la construcción de discursos y la negociación entre actores va decantando las opciones entre las que, finalmente, acaban escogiendo los decisores públicos. El caso de análisis es la decisión adoptada por el gobierno de la ciudad de Madrid ante el aparente conflicto que genera el turismo en la ciudad, aunque el marco teórico y la estrategia de investigación es fácilmente aplicable a otras ciudades que están deliberando sobre estas controversias. Las conclusiones describen un proceso en donde diversos acontecimientos políticos suponen espacios de oportunidad que son aprovechados por algunos actores para impulsar una determinada definición de los problemas y, en consecuencia, una propuesta de intervención coherente con aquella. Observado así el proceso, la racionalidad técnica del decisor tiene un papel muy secundario en el diseño de acciones y la oportunidad política se convierte en elemento clave. Examinar estas dinámicas desde otros marcos teóricos fortalece la capacidad de análisis del turismo como fenómeno transversal y complejo.

BackgroundImported strongyloidiasis is increasingly being diagnosed in non-endemic areas. The aim of this study was to describe the epidemiological, clinical and microbiological characteristics of patients with imported strongyloidiasis in Spain.MethodologyThis is an observational retrospective study that included all patients diagnosed of strongyloidiasis registered in the +REDIVI Collaborative Network from 2009 to 2017. Demographic, epidemiological and clinical information was collected from the +REDIVI database, and extra information regarding microbiological techniques, treatment and follow-up was requested to participant centers.FindingsOverall, 1245 cases were included. Most of them were immigrants (66.9%), and South America was the most frequent area of origin. Detection of larvae in stool samples was observed in 21.9% of the patients, and serological tests allowed making the diagnosis in the rest of the cases. Eosinophilia was present in 82.2% of cases. Treatment with ivermectin (compared with albendazole) was the most strongly associated factor to achieve the cure (OR 2.34).ConclusionsGiven the long latency of the infection and the risk of developing a severe presentation, screening of S. stercoralis infection should be mandatory in patients coming from or had traveling to endemic areas, especially in those with immunosuppressant conditions.

Intraoperative ultrasound elastography (IOUS-E) is a novel image modality applied in brain tumor assessment. However, the potential links between elastographic findings and other histological and neuroimaging features are unknown. This study aims to find associations between brain tumor elasticity, diffusion tensor imaging (DTI) metrics, and cell proliferation. A retrospective study was conducted to analyze consecutively admitted patients who underwent craniotomy for supratentorial brain tumors between March 2018 and February 2020. Patients evaluated by IOUS-E and preoperative DTI were included. A semi-quantitative analysis was performed to calculate the mean tissue elasticity (MTE). Diffusion coefficients and the tumor proliferation index by Ki-67 were registered. Relationships between the continuous variables were determined using the Spearman ρ test. A predictive model was developed based on non-linear regression using the MTE as the dependent variable. Forty patients were evaluated. The pathologic diagnoses were as follows: 21 high-grade gliomas (HGG); 9 low-grade gliomas (LGG); and 10 meningiomas. Cases with a proliferation index of less than 10% had significantly higher medians of MTE (110.34 vs. 79.99, p < 0.001) and fractional anisotropy (FA) (0.24 vs. 0.19, p = 0.020). We found a strong positive correlation between MTE and FA (rs (38) = 0.91, p < 0.001). A cubic spline non-linear regression model was obtained to predict tumoral MTE from FA (R2 = 0.78, p < 0.001). According to our results, tumor elasticity is associated with histopathological and DTI-derived metrics. These findings support the usefulness of IOUS-E as a complementary tool in brain tumor surgery.

Desde las primeras investigaciones sobre turismo diversos autores han prestado atención a la acción de los poderes públicos orientada al fenómeno. Sin embargo existe una notable imprecisión en el uso de cuatro conceptos que designan realidades diferentes: gobierno del turismo, política turística, planificación o gestión pública. El objetivo de este trabajo es reflexionar sobre estos conceptos tratando de comprender cómo se relacionan y delimitando su uso a fenómenos concretos de la acción pública en materia de turismo. Nuestra propuesta es agruparlos en un enfoque relacional o un enfoque racional, cada uno con preguntas propias y con presupuestos determinados, aunque con preocupaciones y propuestas de trabajo muy relacionadas. Mejorar la comprensión de estos conceptos y enfoques nos permitirá desarrollar una agenda de investigación más sólida sobre la acción pública en turismo.

Discussion of the dossier "Policy Change in Latin America: Broadening the Debate"

CD5 and CD6 are closely related signal-transducing class I scavenger receptors mainly expressed on lymphocytes. Both receptors are involved in the modulation of the activation and differentiation cell processes triggered by clonotypic antigen-specific receptors present on T and B cells (TCR and BCR, respectively). To serve such a relevant immunomodulatory function, the extracellular region of CD5 and CD6 interacts with soluble and/or cell-bound endogenous counterreceptors but also microbial-associated molecular patterns (MAMPs). Evidence from genetically-modified mouse models indicates that the absence or blockade of CD5- and CD6-mediated signals results in dysregulated immune responses, which may be deleterious or advantageous in some pathological conditions, such as infection, cancer or autoimmunity. Bench to bedside translation from transgenic data is constrained by ethical concerns which can be overcome by exogenous administration of soluble proteins acting as decoy receptors and leading to transient “functional knockdown”. This review gathers information currently available on the therapeutic efficacy of soluble CD5 and CD6 receptor infusion in different experimental models of disease. The existing proof-of-concept warrants the interest of soluble CD5 and CD6 as safe and efficient immunotherapeutic agents in diverse and relevant pathological conditions.

We report the first human case of West Nile virus (WNV) lineage 2 infection imported to Spain by a traveler returning from Romania. Serum, cerebrospinal fluid and urine samples were analyzed and West Nile virus infection was identified by PCR and serological tests. The patient developed fever, diarrhea and neurological symptoms, accompanied by mild pancreatitis, described previously in very few cases as a complication of WNV infection and by alithiasic cholecystitis. Viral RNA was detected in urine until 30 days after the onset of symptoms and neutralizing antibodies were detected at very low titers. The phylogenetic analysis in a fragment of the NS5 gene of the virus showed a homology with sequences from WNV lineage 2 belonging to the monophyletic Central/Southern European group.

BackgroundScavenger Receptors (SRs) from the host's innate immune system are known to bind multiple ligands to promote the removal of non-self or altered-self targets. CD5 and CD6 are two highly homologous class I SRs mainly expressed on all T cells and the B1a cell subset, and involved in the fine tuning of activation and differentiation signals delivered by the antigen-specific receptors (TCR and BCR, respectively), to which they physically associate. Additionally, CD5 and CD6 have been shown to interact with and sense the presence of conserved pathogen-associated structures from bacteria, fungi and/or viruses.Methodology/principal findingsWe report herein the interaction of CD5 and CD6 lymphocyte surface receptors with Echinococcus granulosus sensu lato (s.l.). Binding studies show that both soluble and membrane-bound forms of CD5 and CD6 bind to intact viable protoscoleces from E. granulosus s.l. through recognition of metaperiodate-resistant tegumental components. Proteomic analyses allowed identification of thioredoxin peroxidase for CD5, and peptidyl-prolyl cis-trans isomerase (cyclophilin) and endophilin B1 (antigen P-29) for CD6, as their potential interactors. Further in vitro assays demonstrate that membrane-bound or soluble CD5 and CD6 forms differentially modulate the pro- and anti-inflammatory cytokine release induced following peritoneal cells exposure to E. granulosus s.l. tegumental components. Importantly, prophylactic infusion of soluble CD5 or CD6 significantly ameliorated the infection outcome in the mouse model of secondary cystic echinococcosis.Conclusions/significanceTaken together, the results expand the pathogen binding properties of CD5 and CD6 and provide novel evidence for their therapeutic potential in human cystic echinococcosis.

Objetivo. Evaluar la dinámica de crecimiento y acumulación de forraje del pasto guinea (P. maximum Jacq.) cv. Mombasa, y definir el momento óptimo de cosecha. Materiales y métodos. Se evaluaron ocho tratamientos, que consistieron en cortes de forraje cada 10 días, durante las cuatro estaciones del año, bajo un diseño completamente al azar con cinco repeticiones. Al inicio de cada estación se realizó corte de uniformidad a 5 cm de altura, y se utilizaron cuadrantes (0.64 m2), para cortar el forraje a ras de suelo. Se evaluó altura de planta, acumulación de forraje, tasa de crecimiento (TC), índice de área foliar, relaciones hoja:tallo y hoja:no hoja, composición botánica y morfológica. Los datos se analizaron mediante Mixed y GLM de SAS. Resultados. La acumulación de forraje fue mayor en verano y primavera (p≤0.05). La acumulación de forraje y la TC incrementaron progresivamente hasta que el crecimiento de las hojas se estabilizó. Los incrementos posteriores de forraje se debieron al aumento de tallos y material muerto cuando la TC declinó. En verano la TC (127 kg MS ha-1d-1) superó en 26, 44 y 75% las TC de primavera, otoño e invierno. Conclusiones. De acuerdo a los resultados (estudios realizados), se sugiere que, en esta región del Estado de Chiapas, el manejo óptimo del cv. Mombasa y su mayor producción de forraje, se obtiene al cosechar cada 40, 50, 40 y 30 días en primavera, verano, otoño e invierno, respectivamente.

A defining pathophysiological hallmark of Alzheimer’s disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Aβ1-42 peptides. Amyloid plaques are hard, brittle structures scattered throughout the hippocampus and cerebral cortex and are thought to cause hyperphosphorylation of tau, neurofibrillary tangles, and progressive neurodegeneration. Reactive astrocytes and microglia envelop the exterior of amyloid plaques and infiltrate their inner core. Glia are highly mechanosensitive cells and can almost certainly sense the mismatch between the normally soft mechanical environment of the brain and very stiff amyloid plaques via mechanosensing ion channels. Piezo1, a non-selective cation channel, can translate extracellular mechanical forces to intracellular molecular signaling cascades through a process known as mechanotransduction. Here, we utilized an aging transgenic rat model of AD (TgF344-AD) to study expression of mechanosensing Piezo1 ion channels in amyloid plaque-reactive astrocytes. We found that Piezo1 is upregulated with age in the hippocampus and cortex of 18-month old wild-type rats. However, more striking increases in Piezo1 were measured in the hippocampus of TgF344-AD rats compared to age-matched wild-type controls. Interestingly, repeated urinary tract infections with Escherichia coli bacteria, a common comorbidity in elderly people with dementia, caused further elevations in Piezo1 channel expression in the hippocampus and cortex of TgF344-AD rats. Taken together, we report that aging and peripheral infection augment amyloid plaque-induced upregulation of mechanoresponsive ion channels, such as Piezo1, in astrocytes. Further research is required to investigate the role of astrocytic Piezo1 in the Alzheimer’s brain, whether modulating channel opening will protect or exacerbate the disease state, and most importantly, if Piezo1 could prove to be a novel drug target for age-related dementia.

To gain insight into the importance of carefully selecting the sampling area for intestinal microbiota studies, cecal and fecal microbial communities of Caldes meat rabbit were characterized. The animals involved in the study were divided in two groups according to the feed intake level they received during the fattening period; ad libitum (n = 10) or restricted to 75% of ad libitum intake (n = 11). Cecum and internal hard feces were sampled from sacrificed animals. Assessment of bacterial and archaeal populations was performed by means of Illumina sequencing of 16S rRNA gene amplicons in a MiSeq platform. A total of 596 operational taxonomic units (OTUs) were detected using QIIME software. Taxonomic assignment revealed that microbial diversity was dominated by phyla Firmicutes (76.42%), Tenericutes (7.83%), and Bacteroidetes (7.42%); kingdom Archaea was presented at low percentage (0.61%). No significant differences were detected between sampling origins in microbial diversity or richness assessed using two alpha-diversity indexes: Shannon and the observed number of OTUs. However, the analysis of variance at genus level revealed a higher presence of genera Clostridium, Anaerofustis, Blautia, Akkermansia, rc4-4, and Bacteroides in cecal samples. By contrast, genera Oscillospira and Coprococcus were found to be overrepresented in feces, suggesting that bacterial species of these genera would act as fermenters at the end of feed digestion process. At the lowest taxonomic level, 83 and 97 OTUs in feces and cecum, respectively, were differentially represented. Multivariate statistical assessment revealed that sparse partial least squares discriminant analysis (sPLS-DA) was the best approach for this purpose. Interestingly, the majority of the most discriminative OTUs selected by sPLS-DA were found to be differentially represented between sampling origins in univariate analysis. Our study provides evidence that the choice of intestinal sampling area is relevant due to important differences in some taxa’s relative abundance that have been revealed between rabbits’ cecal and fecal microbiota. An appropriate sampling intestinal area should be chosen in each microbiota assessment.

Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM) and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.

El artículo se basa en una investigación sobre las posibilidades de crear un órgano de gestión del destino, de carácter mixto, para la gestión turística de Aranjuez. Se argumenta que para elegir el mejor modelo de órgano de gestión turística para un destino es necesario investigar tres categorías: caracterización del turismo, importancia relativa del turismo y madurez colaborativa de los actores turísticos del destino. La conclusión es que no existe un modelo de órgano de gestión mixta que pueda ser implantado en cualquier destino turístico, siendo el contexto específico y sus condiciones los que acaban aconsejando qué tipo de institución de gestión de destino es posible diseñar e implantar.

Manuel Sánchez de Dios. Síntesis. 2012, 322 pp.

El presente texto pretende profundizar en el debate sobre la naturaleza, contenidos e instrumentos de la política turística, ampliando las perspectivas científicas que trabajan sobre este asunto y tratando de mejorar el entendimiento de las decisiones públicas relacionadas con el turismo. Utilizando el Análisis de Políticas como perspectiva de análisis es posible proponer una definición de política turística operativa, enumerar cuáles son los elementos constitutivos de este tipo de acción pública y describir los instrumentos que pueden ser combinados por los decisores públicos para que, a través de la política diseñada, se alcancen los fines propuestos.

La gestión turística del patrimonio cultural es la aplicación de conocimientos específicos para la adecuación de bienes de patrimonio cultural en recursos turísticos. El punto de partida es, en razón de los bienes de los que estamos hablando, la conservación de los mismos y la preservación del espíritu que representan. Pero esto ha de ser combinado con el hecho de que el patrimonio vive una creciente presión para ser adaptado a un uso turístico, hecho relacionado con el progresivo aumento del turismo cultural. La utilización de algunos instrumentos básicos permitirá que los procesos de interacción entre el sector turístico y el sector del patrimonio cultural permitan, no solo encontrar el equilibrio entre ambos, sino mejorar el rendimiento de los dos sectores.

This paper examines in detail the evolution of tourism policies implemented by different Spanish governments since the Fifties until 2004. The chosen method of study is Policy Analysis. Following its rules, different regulatory systems are highlighted, marking similarities and discontinuities. Finally a periodization is proposed according to the main goals of every government.Este trabajo sigue en detalle la evolución de la política turística de los diferentes gobiernos españoles desde la creación del Ministerio de Información y Turismo hasta el final del Gobierno del Partido Popular. Se analizan los diversos sistemas de regulación a la luz del método de Análisis de Políticas, así como sus semejanzas y discontinuidades. Finalmente se procede a una periodización de su evolución.