Evolutionarily diverse origins of deformed wing viruses in western honey bees.

Novel transmission routes can allow infectious diseases to spread, often with devastating consequences. Ectoparasitic varroa mites vector a diversity of RNA viruses, having switched hosts from the eastern to western honey bees (Apis cerana to Apis mellifera). They provide an opportunity to explore how novel transmission routes shape disease epidemiology. As the principal driver of the spread of deformed wing viruses (mainly DWV-A and DWV-B), varroa infestation has also driven global honey bee health declines. The more virulent DWV-B strain has been replacing the original DWV-A strain in many regions over the past two decades. Yet, how these viruses originated and spread remains poorly understood. Here, we use a phylogeographic analysis based on whole-genome data to reconstruct the origins and demography of DWV spread. We found that, rather than reemerging in western honey bees after varroa switched hosts, as suggested by previous work, DWV-A most likely originated in East Asia and spread in the mid-20th century. It also showed a massive population size expansion following the varroa host switch. By contrast, DWV-B was most likely acquired more recently from a source outside East Asia and appears absent from the original varroa host. These results highlight the dynamic nature of viral adaptation, whereby a vector's host switch can give rise to competing and increasingly virulent disease pandemics. The evolutionary novelty and rapid global spread of these host-virus interactions, together with observed spillover into other species, illustrate how increasing globalization poses urgent threats to biodiversity and food security.

Detection of Microsporidia in Pollinator Communities of a Mediterranean Biodiversity Hotspot for Wild Bees.

Insect pollination is crucial for the maintenance of natural and managed ecosystems but the functioning of this ecosystem service is threatened by a worldwide decline of pollinators. Key factors in this situation include the spread and interspecific transmission of pathogens worldwide through the movement of managed pollinators. Research on this field has been mainly conducted in some particular species, while studies assessing the interspecific transmission of pathogens at a community level are scarce. However, this information is pivotal to design strategies to protect pollinators. Herein, we analysed the prevalence of two common microsporidia pathogens of managed honey bees (Nosema ceranae and N. apis) in bee communities of semiarid Mediterranean areas from the Southeast of the Iberian Peninsula. Our results confirm the ability of N. ceranae to disperse across wild bee communities in semiarid Mediterranean ecosystems since it was detected in 36 Apoidea species (39% of the sampling; for the first time in nine genera). The prevalence of the pathogen did not show any phylogenetic signal which suggests a superfamily host range of the pathogen or that wild bees may be acting only as vectors of N. ceranae. In addition, N. apis was detected in an Eucera species, which is the second time it has been detected by molecular techniques in a host other than the honey bee. Our study represents the primary assessment of the prevalence of microsporidia at community level in Mediterranean areas and provides outstanding results on the ability of Nosema pathogens to spread across the landscape.

Online Mindfulness Experience for Emotional Support to Healthcare staff in times of Covid-19.

During the first confinement in Spain, between the months of March to June 2020, Information and Communication Technologies strategies were implemented in order to support health workers in the Wellbeing of Mental Health. Faced with so much uncertainty about the pandemic, an Online Mindfulness course. The objective of the course was to support healthcare professionals in Castilla y León in managing stress, anxiety and other emotional disturbances generated by coping with a situation as uncertain and unexpected as a pandemic, in order to manage emotions and thoughts that can lead to suicidal ideation. The motivations for the demand, reasons or motivations in which the health professionals of Castilla y León decided to participate in the mindfulness course in the first wave of Covid-19 in Spain are described. The descriptive and inferential statistical analysis of the customer satisfaction survey applied at the end of the mindfulness course, to the health professionals who participated in a satisfaction survey (CSQ-8: Client Satisfaction Questionnaire). Professional were asked to complete a survey based on (CSQ-8: Client Satisfaction Questionnaire) whose Cronbach's alpha = 0.917 is why the instrument used with N = 130 participants has high reliability. The 66% answered with a highly satisfied that they would return to the mindfulness online course. The 93% of the people who answered the satisfaction survey were women, of which they are professionals in the nursing area, with a participation of around 62%. In relation to the online system used in the Mindfulness intervention, 74% expressed that they fully agreed that it has been easy to use the online system for the mindfulness intervention. Health Professionals responded with 58% high satisfaction and 36% satisfaction, making a total of 94% on the help received in the online mindfulness courses to solve their problems. There is no difference between the age groups of the professionals who have preferred the Mindfulness online course (p = 0.672).

The communication skills and quality perceived in an emergency department: The patient's perspective.

AIM: To examine the influence of health care provider's communication skills on the quality of care perceived by Emergency Department patients. BACKGROUND: Communication between patients and health care providers in the context of Emergency Department is challenging and can potentially have a negative impact on the quality of care perceived by patients. DESIGN: Cross-sectional descriptive study conducted in the Emergency Department at the University Clinical Hospital Virgen de la Arrixaca of Murcia, Spain. METHOD: Data were collected from 6 to 9 June 2016. Different instruments were used to evaluate the perception of patients on the communication skills and quality of care at the Emergency Department. RESULTS: The sample was composed of 200 patients, with an average age of 44.1 (SD = 18.3), of which 106 (53%) were men. The multiple linear regression analysis showed the association between communication skills (respect, problem solving, and nonverbal communication) and age with the quality of care perceived by the patients. CONCLUSIONS: We found that the communication skills of the health care providers were explanatory variables of the quality of care perceived in an Emergency Department.

Coexistence of genetically different Varroa destructor in Apis mellifera colonies.

The aim of this study was to investigate the genetic diversity of Varroa destructor parasitizing Apis mellifera colonies and to test for possible host-parasite association at the mitochondrial DNA (mtDNA) level. Six A. mellifera haplotypes (including a novel C2aa) and five haplotypes of V. destructor were detected in 29 analyzed colonies from eight sampling sites in Serbia. We revealed the presence of the K and S1 haplotypes as well as KS1 and KP1 heteroplasmic mite individuals in all localities, while the P1 haplotype was only found in four sampling sites. Significant differences in V. destructor genetic diversity were found at both apiary and colony levels, with mite haplotypes coexisting in almost all tested colonies. In addition, a significant correlation between the number of analyzed mites per colony and the number of identified V. destructor haplotypes was observed. However, no significant host-parasite relationship was found, suggesting that mites bearing different haplotypes as well as those heteroplasmic individuals are well adapted to the host, A. mellifera, independently of the identified haplotype present in each colony. Our results will contribute to future population and biogeographic studies concerning V. destructor infesting A. mellifera, as well as to better understanding their host-parasite relationship.

Stress, Coping, and Personality in Patients with Epicrania Fugax, and Their Relation to the Clinical Characteristics of Pain.

Objective: The aim of the present work is to analyze certain psychological features in a group of patients diagnosed with Epicrania fugax (EF; that has been recently included in the appendix of the International Classification of Headache Disorders, third edition, beta version), as well as their association with diverse demographic and clinical characteristics of the sample. Design: Case-control. Method: Perceived Stress Scale (PSS), Stress Coping (COPE), Big Five Personality Traits (NEO-FFI), Depression (BDI-II), and Trait Anxiety (STAI) were evaluated in 23 patients with EF and 23 matched healthy controls. Differences between EF patients and controls were analyzed using the Mann-Whitney U test. Differences in psychological features as a function of the demographic and clinical characteristics were examined using one-way Analysis of Variance (ANOVA), Mann-Whitney U test, or Pearson's correlations. Results: The two groups differed significantly from each other in Denial, Trait anxiety, and Depression. Low-frequency epicrania patients scored significantly higher than controls in Perceived stress, Neuroticism, Denial, Self-blame, Trait anxiety, and Depression and higher than high-frequency EF in Venting. Conclusions: The results initially suggest the absence of substantial differences between patients suffering of EF and healthy controls. On the contrary, low-frequency EF patients show a distinctive "negative (unhealthy) psychological profile," in opposition to high-frequency EF patients. This circumstance highlights the potential need to consider low- frequency EF patients as a target for psychological intervention in combination with the most common medical procedures. Longitudinal studies are necessary to correctly elucidate the influence of these psychological variables on the course of EF.

Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies.

Antibody cancer therapies rely on systemically accessible targets and suitable antibodies that exert a functional activity or deliver a payload to the tumor site. Here, we present proof-of-principle of in vivo selection of human antibodies in tumor-bearing mice that identified a tumor-specific antibody able to deliver a payload and unveils the target antigen. By using an ex vivo enrichment process against freshly disaggregated tumors to purge the repertoire, in combination with in vivo biopanning at optimized phage circulation time, we have identified a human domain antibody capable of mediating selective localization of phage to human prostate cancer xenografts. Affinity chromatography followed by mass spectrometry analysis showed that the antibody recognizes the proteasome activator complex PA28. The specificity of soluble antibody was confirmed by demonstrating its binding to the active human PA28αß complex. Whereas systemically administered control phage was confined in the lumen of blood vessels of both normal tissues and tumors, the selected phage spread from tumor vessels into the perivascular tumor parenchyma. In these areas, the selected phage partially colocalized with PA28 complex. Furthermore, we found that the expression of the α subunit of PA28 [proteasome activator complex subunit 1 (PSME1)] is elevated in primary and metastatic human prostate cancer and used anti-PSME1 antibodies to show that PSME1 is an accessible marker in mouse xenograft tumors. These results support the use of PA28 as a tumor marker and a potential target for therapeutic intervention in prostate cancer.

Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway and proinflammatory response in human pericytes.

Pericytes and mesenchymal stem cells (MSCs) are ontogenically related, and in fact, no significant phenotypic differences could be observed by flow cytometry. Transcriptome analysis of human pericytes and MSCs revealed that 43 genes were up-regulated more than 10-fold in pericytes compared with MSCs. Identification of Toll-like receptor 4 (TLR4) as one of the most abundant RNA species in pericytes with respect to MSCs and confirmation of TLR4 expression on the cell surface led us to obtain a comprehensive overview of the expression program of lipopolysaccharide (LPS)-stimulated pericytes. Transcriptional profiling of LPS-treated cells revealed that 22 genes were up-regulated more than 5-fold. Of them, 10 genes encoded chemokines and cytokines (CXCL10, CCL20, IL8, CXCL1, IL6, CCL2, IL1B, CXCL2, IL1A, and CXCL6), and three genes encoded adhesion molecules (ICAM1, VCAM1, and SELE). LPS induced nuclear translocation of the transcription factor NF-κB in stimulated pericytes. Moreover, inhibition of NF-κB activation by SC-514 blocked LPS-induced up-regulation of a subset of chemokine genes, confirming the key role of NF-κB in LPS signaling in pericytes. At the protein level, we assessed the secretion of the proinflammatory cytokines and chemokines IL-6, IL-8, CXCL1, CXCL2, CXCL3, and CCL2 not only after LPS treatment but also in HMGB1-stimulated pericytes. Up-regulation of the adhesion molecules ICAM-1 and VCAM-1 resulted in an increased adhesion of peripheral blood leukocytes to an LPS-treated pericyte monolayer. The role of pericytes in the inflammatory context has been scarcely addressed; according to these results, pericytes should be considered as active players in the inflammatory cascade with potential physiopathological implications.

Stable genetic diversity despite parasite and pathogen spread in honey bee colonies.

In the last decades, the rapid spread of diseases, such as varroosis and nosemosis, associated with massive honey bee colonies mortality around the world has significantly decreased the number and size of honey bee populations and possibly their genetic diversity. Here, we compare the genetic diversity of Iberian honey bee colonies in two samplings performed in 2006 and 2010 in relation to the presence of the pathogenic agents Nosema apis, Nosema ceranae, and Varroa destructor in order to determine whether parasite and pathogen spread in honey bee colonies reflects changes in genetic diversity. We found that the genetic diversity remained similar, while the incidence of N. ceranae increased and the incidence of N. apis and V. destructor decreased slightly. These results indicate that the genetic diversity was not affected by the presence of these pathogenic agents in the analyzed period. However, the two groups of colonies with and without Nosema/Varroa detected showed significant genetic differentiation (G test). A detailed analysis of the allelic segregation of microsatellite loci in Nosema/Varroa-negative colonies and parasitized ones revealed two outlier loci related to genes involved in immune response.

From wakefulness to sleep: migraine and hypnic headache association in a series of 23 patients.

OBJECTIVES/BACKGROUND: We analyzed characteristics of hypnic headache (HH), migraine and the relationship between both headaches in 23 patients. HH is an uncommon primary headache characterized by exclusively sleep-related attacks. Concurrence of other headaches, mainly migraine, has been reported, but relationship between both syndromes has rarely been considered. METHODS: We prospectively collected data in a headache outpatient office from January 2008 to September 2013. Demographic data and migraine and hypnic headache mean features were assessed. RESULTS: Twenty-three out of 2500 (0.92%) were diagnosed with HH or probable HH, and 16 of them (69.5%) had a history of migraine. Mean age at onset of HH and migraine was 56.2 ± 9.3 and 24.6 ± 12.2 years, respectively. In 12 cases, migraine attacks disappeared at 56.7 ± 9.8 years old. Regarding the relationship between both syndromes, in 10 patients, migraine disappeared and HH began immediately after. In 1 case there was a pain-free period, and in 5 an overlap between both headaches was registered. CONCLUSION: A history of migraine is common in HH patients in our series. Most frequent transition pattern was an immediate change between both syndromes. Hypnic headache and migraine might share a common pathophysiological predisposition.

Climate rather than geography separates two European honeybee subspecies.

Both climatic and geographical factors play an important role for the biogeographical distribution of species. The Carpathian mountain ridge has been suggested as a natural geographical divide between the two honeybee subspecies Apis mellifera carnica and A. m. macedonica. We sampled one worker from one colony each at 138 traditional apiaries located across the Carpathians spanning from the Hungarian plains to the Danube delta. All samples were sequenced at the mitochondrial tRNA(Leu)-cox2 intergenic region and genotyped at twelve microsatellite loci. The Carpathians had only limited impact on the biogeography because both subspecies were abundant on either side of the mountain ridge. In contrast, subspecies differentiation strongly correlated with the various temperature zones in Romania. A. m. carnica is more abundant in regions with the mean average temperature below 9 °C, whereas A. m. macedonica honeybees are more frequent in regions with mean temperatures above 9 °C. This range selection may have impact on the future biogeography in the light of anticipated global climatic changes.

Assessment of effectiveness of acoustic analysis of voice for monitoring the evolution of vocal nodules after vocal treatment.

In the present study, we report the results of acoustic analysis of voice in 97 patients diagnosed with vocal nodules before and after the vocal logopedic treatment, to evaluate its effectiveness in monitoring the evolution. We analyzed five parameters: the mean fundamental frequency (F0) and its standard deviation, jitter, shimmer, and normalized noise energy (NNE). Our results indicate that most patients showed a reduction of fundamental frequency, an increase of perturbation (jitter and shimmer), and an increase of NNE before the treatment. We did not find any statistically significant relationship between previous values of the five parameters analyzed and the clinical course. We did not find significant differences between the two groups (with and without clinical improvement) in the evolution of any of the five parameters, although these differences were greater in the case of jitter. We conclude that the acoustic analysis of voice can be useful as a complementary tool in the diagnosis of vocal nodules, but the parameter values analyzed before treatment did not correlate with the clinical course and we believe that its usefulness in the evaluation of results after the vocal treatment is limited.

Conserving genetic diversity in the honeybee: comments on Harpur et al. (2012).

The article by Harpur et al. (2012) 'Management increases genetic diversity of honey bees via admixture' concludes that '…honey bees do not suffer from reduced genetic diversity caused by management and, consequently, that reduced genetic diversity is probably not contributing to declines of managed Apis mellifera populations'. In the light of current honeybee and beekeeping declines and their consequences for honeybee conservation and the pollination services they provide, we would like to express our concern about the conclusions drawn from the results of Harpur et al. (2012). While many honeybee management practices do not imply admixture, we are convinced that the large-scale genetic homogenization of admixed populations could drive the loss of valuable local adaptations. We also point out that the authors did not account for the extensive gene flow that occurs between managed and wild/feral honeybee populations and raise concerns about the data set used. Finally, we caution against underestimating the importance of genetic diversity for honeybee colonies and highlight the importance of promoting the use of endemic honeybee subspecies in apiculture.

Signatures of selection in the Iberian honey bee (Apis mellifera iberiensis) revealed by a genome scan analysis of single nucleotide polymorphisms.

Understanding the genetic mechanisms of adaptive population divergence is one of the most fundamental endeavours in evolutionary biology and is becoming increasingly important as it will allow predictions about how organisms will respond to global environmental crisis. This is particularly important for the honey bee, a species of unquestionable ecological and economical importance that has been exposed to increasing human-mediated selection pressures. Here, we conducted a single nucleotide polymorphism (SNP)-based genome scan in honey bees collected across an environmental gradient in Iberia and used four FST -based outlier tests to identify genomic regions exhibiting signatures of selection. Additionally, we analysed associations between genetic and environmental data for the identification of factors that might be correlated or act as selective pressures. With these approaches, 4.4% (17 of 383) of outlier loci were cross-validated by four FST -based methods, and 8.9% (34 of 383) were cross-validated by at least three methods. Of the 34 outliers, 15 were found to be strongly associated with one or more environmental variables. Further support for selection, provided by functional genomic information, was particularly compelling for SNP outliers mapped to different genes putatively involved in the same function such as vision, xenobiotic detoxification and innate immune response. This study enabled a more rigorous consideration of selection as the underlying cause of diversity patterns in Iberian honey bees, representing an important first step towards the identification of polymorphisms implicated in local adaptation and possibly in response to recent human-mediated environmental changes.

Early maladaptive schemas as a risk factor for fibromyalgia: A case-control study.

OBJECTIVE: There is evidence supporting the relationship between early stress and childhood trauma and the development of fibromyalgia (FM). Early maladaptive schemas (EMSs) are considered a consequence of early stress. Previous research has shown their role in maintaining stress responses and their relevance in other populations with pain. The main aim of this study has been to analyze the presence of EMSs in patients with FM compared to healthy adult women. In addition, the relationship between the strength of EMSs and pain intensity was tested. METHOD: The total sample consisted of 167 women: 83 patients with FM and 84 healthy controls. RESULTS: Chi-square analyses showed that the percentage of participants with clinically significant scores is higher for patients with FM in 11 of the 18 EMSs evaluated. Moreover, discriminant analyses revealed that these EMS are useful to discriminate between FM and healthy controls, classifying 74.2% of original cases. In relation to the second aim, the mean pain intensity correlated with the strength of several EMSs: approval seeking, unrelenting standards, insufficient self-control, and mistrust/abuse. CONCLUSIONS: The current study highlights that a high rate of patients with FM have clinically significant EMSs compared to healthy matched controls, as has been found in other populations with pain. Besides, this study provides initial evidence that EMSs are positively associated with the pain experienced by patients with FM, suggesting the existence of a possible association between early stress and pain. Therefore, taking EMSs into account could be of great relevance to clinicians. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Novel Microsatellite Loci, Cross-Species Validation of Multiplex Assays, and By-Catch Mitochondrial Genomes on Ochthebius Beetles from Supratidal Rockpools.

Here we focus on designing, for the first time, microsatellite markers for evolutionary and ecological research on aquatic beetles from the genus Ochthebius (Coleoptera, Hydraenidae). Some of these non-model species, with high cryptic diversity, exclusively inhabit supratidal rockpools, extreme and highly dynamic habitats with important anthropogenic threats. We analysed 15 individuals of four species (O. lejolisii, O. subinteger, O. celatus, and O. quadricollis) across 10 localities from the Mediterranean coasts of Spain and Malta. Using next-generation sequencing technology, two libraries were constructed to interpret the species of the two subgenera present consistently (Ochthebius s. str., O. quadricollis; and Cobalius, the rest of the species). Finally, 20 markers (10 for each subgenus) were obtained and successfully tested by cross-validation in the four species under study. As a by-catch, we could retrieve the complete mitochondrial genomes of O. lejolisii, O. quadricollis, and O. subinteger. Interestingly, the mitochondrial genome of O. quadricollis exhibited high genetic variability compared to already published data. The novel SSR panels and mitochondrial genomes for Ochthebius will be valuable in future research on species identification, diversity, genetic structure, and population connectivity in highly dynamic and threatened habitats such as supratidal coastal rockpools.

[Factors associated with the duration of SARS-CoV-2 infection in healthcare professionals at a second-level public hospital in the Community of Madrid (Spain) during the sixth wave.] / Factores asociados a la duración de la infección por SARS-CoV-2 en profesionales sanitarios de un hospital público de segundo nivel de la Comunidad de Madrid durante la sexta ola.

OBJECTIVE: The incidence of COVID-19 infections among health professionals during the sixth wave has suffered an exponential increase, mainly due to the rapid community transmission caused by the Omicron variant. The main objective of the study was to evaluate the time to negativization in COVID-positive health professionals during the sixth wave, according to the PDIA result; and secondarily, to evaluate the possible influence of other factors (previous infection, vaccination, sex, age, job position) on the time to get negative status. METHODS: A descriptive, longitudinal, observational and retrospective study was carried out at Infanta Sofía University Hospital (Madrid, Spain). Made from the registry of the Occupational Risk Prevention Service of suspected or confirmed cases of SARS-COV-2 infection in health professionals, during the period between November 1, 2021 and February 28, 2022. Bivariate comparisons were made using Mann Whitney, Kruskal Wallis or Chi-square test (or exact test) according to variables. Subsequently, logistic regression (explanatory model) was performed. RESULTS: The cumulative incidence of SARS-COV-2 infection in health professionals was 23.07%. The mean time to become negative was 9.94 days. Only the history of previous SARS-COV-2 infection had a statistically significant influence on the time to negativization of PDIA. The variables vaccination, sex and age had no effect on the time to negativization of PDIA. CONCLUSIONS: Professionals with a history of COVID-19 infection present lower times of negativization than those who had not have the disease. The results of our study confirm the immune escape of the vaccine against COVID-19, since more than 95% of those infected had received a complete vaccination schedule.

OBJETIVO: La incidencia de contagios por COVID-19 entre profesionales sanitarios durante la sexta ola, ha sufrido un incremento exponencial motivado principalmente por la rápida trasmisión comunitaria ocasionada por la variante Ómicron. El objetivo principal del estudio fue evaluar el tiempo de negativización en los profesionales sanitarios COVID positivos durante la sexta ola, según resultado de PDIA; y, de forma secundaria, evaluar la posible influencia de otros factores (infección previa, vacunación, sexo, edad, puesto de trabajo) en el tiempo de negativización. METODOS: Se realizó un estudio descriptivo, longitudinal, observacional y retrospectivo en el Hospital Universitario Infanta Sofía (Madrid), a partir del registro del Servicio de Prevención de Riesgos Laborales de casos sospechosos o confirmados de infección por SARS-COV-2 en profesionales sanitarios, durante el periodo comprendido entre el 1 de noviembre de 2021 y el 28 de febrero de 2022. Se hicieron comparaciones bivariadas mediante Mann Whitney, Kruskal Wallis o test de Chi-cuadrado (o test exacto) según variables. Posteriormente se realizó regresión logística (modelo explicativo). RESULTADOS: La incidencia acumulada de infección por SARS-COV-2 en profesionales sanitarios fue del 23,07%. El tiempo medio en negativizar fue de 9,94 días. Únicamente el antecedente de infección previa por SARS-COV-2 influyó de forma estadísticamente significativa en el tiempo de negativización de PDIA. Las variables vacunación, sexo y edad no tuvieron efecto en el tiempo de negativización de PDIA. CONCLUSIONES: Los profesionales con antecedente de infección por COVID-19 presentan tiempos inferiores de negativización que aquellos que no han pasado la enfermedad. Los resultados de nuestro estudio constatan el escape inmunológico de la vacuna frente al COVID-19, pues más del 95% de los infectados habían recibido una pauta de vacunación completa.

Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of Clostridioides difficile infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial.

INTRODUCTION: Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT. METHODS AND ANALYSIS: We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: NCT05320068.

Hemicrania continua in a headache clinic: referral source and diagnostic delay in a series of 22 patients.

Hemicrania continua (HC) is a unilateral and continuous primary headache with superimposed exacerbations frequently associated with autonomic features. Diagnostic criteria of HC, according to II Edition of International Classification of Headache Disorders require complete response to indomethacin. HC is probably misdiagnosed more often than other primary headaches. We aim to analyze characteristics of a series of 22 consecutive cases of HC. We recruited patients from a headache outpatient clinic in a tertiary hospital over a 3-year period (January 2008 to January 2011). We prospectively gathered demographic and nosological characteristics and considered referral source and delay between onset of headache and diagnosis of HC. Twenty-two patients (14 females, 8 males) out of 1,150, who attended the mentioned clinic during the inclusion period (1.9 %) were diagnosed with HC. All cases responded to indomethacin. No patient received a diagnosis of HC before attending our headache office. Mean latency of diagnosis was 86.1 ± 106.5 months (range 3-360). 11 patients (50 %) were referred from primary care, with 9 (40.9 %) from other neurology clinics and 2 (9.1 %) from other specialities offices. According to our series, HC is not an infrequent diagnosis in a headache outpatient clinic. Diagnostic delay is comparable to data collected in previous studies. As HC is frequently misdiagnosed, we thing there is a need for increasing the understanding of this entity, potentially responsive to indomethacin.

Recolonization origin and reproductive locations, but not isolation from the sea, lead to genetic structure in migratory lagoonal fishes.

The assessment of connectivity in marine ecosystems is a requirement to adequate fisheries management. In this study we have selected two commercially exploited migratory species, European perch (Perca fluviatilis) and European smelt (Osmerus eperlanus), to evaluate the connectivity between the Curonian Lagoon and the coastal Baltic Sea. Our results indicate that isolation between the coastal lagoon and the adjacent sea area does not lead to the formation of genetic structure in migratory fish species. However, both species do register subpopulations coexisting in the area without interbreeding. This indicates that the fisheries management for migratory fishes in coastal lagoons affects a wider area than just the coastal lagoon. European perch, being a postglacial recolonizer from various refugees, has four different subpopulations, while the mechanism that maintains this division remains unexplored. The feeding migrations of European perch to the coastal zone suggest that the reproduction might occur elsewhere and that the factors for genetic structure suggested at the Baltic Sea scale might operate during these migrations. For European smelt, we discuss the existence of two different ecotypes, one lagoonal and one diadromous, and the different registered spawning locations as explicative causes for the maintenance of two genetically divergent clusters. The lagoonal ecotype reproduces and spawns inside the Curonian Lagoon while the diadromous one lives in the open Baltic Sea, performing spawning migrations to the lagoon and the mouth of Nemunas river, thus, maintaining the genetic divergence among them. However, our results indicate that there are no differences in size between both clusters, while the lagoonal population is expected to be smaller, forbidding the determination of two genetically different ecotypes. We conclude that there are no geographically and genetically separated populations of these two species in the lagoon-sea- terrestrial inlets continuum, and unified stock management for the coastal Baltic Sea and the Curonian lagoon is required.