Effectiveness of an educational intervention about inhalation technique in healthcare professionals in primary care: a cluster randomized trial.

Background: Incorrect inhalation technique (IT) is an important issue for chronic obstructive pulmonary disease (COPD) patients and healthcare professionals. Studies in which counseling is carried out with healthcare professionals beforehand so that they can properly educate their patients are required. The objective of the present trial is to assess the improvement in the performance of the IT in subjects with COPD and prescribed inhaled therapy after the implementation of an educational intervention conducted by their general practitioners. Methods: A cluster randomized clinical trial was conducted. A total of 286 COPD patients received scheduled inhalation therapy from 27 general practices in seven primary care centers. A teach-back educational intervention was implemented for both healthcare professionals and patients. The primary outcome of this study was the performance of the correct inhalation technique. It is considered a good technique if all steps in the inhalation data sheet are correctly performed. The secondary outcomes were assessed using forced spirometry, the basal dyspnea index, the Medical Research Council dyspnea scale, St George's Respiratory Questionnaire (SGRQ), and EuroQoL5D-5L for health-related quality of life. A one-year follow-up was conducted using an intention-to-treat analysis. Results: After the intervention, incorrect IT was observed in 92% of professionals and patients, with rates reaching 50% and 69.2%, respectively. The effectiveness in patients was significant, with a number needed to treat of 2.14 (95% CI 1.79-2.66). Factors related to correct IT in patients included the type of intervention, length of intervention (>25 min), good pulmonary function, age (youngest <=65, oldest >83), and less limitation of activity due to dyspnea. There was no relation with the cluster. Conclusion: This study shows the effectiveness of direct inhaler technique training provided by a trained professional on an appropriate timescale (for example, a specific consultation for medication reviews), aiming to help subjects improve their performance using the teach-back method. This could be an encouraging intervention to improve medication adherence and health promotion in people with COPD. Clinical Trial Registration: clinicaltrials.gov, identifier ISRCTN93725230.

The PREDG study: A randomised controlled trial testing whether an educational intervention can prevent gestational weight gain in women with obesity.

OBJECTIVE: The PREDG trial was designed to study the influence of an educative program on gestational weight gain in women with pregestational obesity. METHODS: Randomized controlled clinical trial (https://www.isrctn.com/ISRCTN61793947) in 169 women with pregestational obesity (BMI ≥30 kg/m2). Women were randomized to participate in a group education program in nutrition and physical activity or conventional follow-up in a specialized Unit of Obesity and Pregnancy. The nutritional intervention was adjusted to prepregnancy BMI and to the physical activity intensity. Quality was based on the Mediterranean diet. Macronutrients were distributed as follows: 50% carbohydrates, 20% protein and 30% fat. Adequate gestational weight gain was defined between 5 and 9 kg (IOM 2009). Mean gestational weight gain was compared between groups by using the T Student test and frequencies of adequate gestational weight gain were compared by using ꓫ2. RESULTS: Gestational weight gain was lower in the intervention group: 8 (4-11) vs 9.2 (6-13) kg, p 0.026. Gestational weight gain was below 9 kg in 24 of 39 (61.5%) women of the intervention vs 10 of 41 (24.4%) of the control group (p 0.001). Regarding obstetric complications, there were 15 (8.3%) cases of gestational diabetes with no differences between the groups. There were 14 of 85 (18.2%) cases of gestational hypertension or preeclampsia in the intervention group compared with 26 of 84 (32.5%) in the control group (p 0.040). With reference to neonatal weight, there were 7 of 82 (8.5%) large for gestational age neonates in the intervention group compared with 15 of 79 (19.2%) in the control group (p 0.050). CONCLUSIONS: A group-based educative and structured intervention results in an adequate weight gain and lower rates of gestational hypertension, preeclampsia and large for gestational age neonates in pregnant women with obesity.

Impact of COVID-19 pandemic on HbA1c management and results in pediatric and adult outpatients with diabetes.

Objectives: Diabetes mellitus intensify the risks and complications related to COVID-19 infection. A major effect of the pandemic has been a drastic reduction of in-person visits. The aim of this study was to evaluate the impact of the COVID-19 pandemic on HbA1c management and results among pediatric and adult outpatients with diabetes, considering the laboratory and point-of-care testing (POCT) HbA1c measurements. Methods: Observational retrospective study including patients from pediatric and adult diabetes units was conducted. HbA1c results obtained in the laboratory and POCT over 3 years (2019-2021) were collected from the laboratory information system. Results: After the lockdown, the number of HbA1c plummeted. Children returned soon to routine clinical practice. The number of HbA1c increased gradually in adults, especially in POCT. Globally, HbA1c results were lower in children compared with adults (p<0.001). HbA1c values in children (p<0.001) and adults (p=0.002) decreased between pre-pandemic and post-pandemic periods, though lower than the HbA1c reference change value. The percentage of HbA1c results above 8% remained stable during the study period. Conclusions: Continuous glucose monitoring and a telemedicine have been crucial, even allowing for improvements in HbA1c results. During the lockdown, patients with better metabolic control were managed in the laboratory whereas patients with poorer control or a severe clinical situation were attended in diabetes units by POCT. Adults returned to pre-pandemic management slowly because they were more susceptible to morbidity and mortality due to COVID-19. Coordination among all health professionals has been essential to offering the best management, especially in difficult scenarios such as the COVID-19 pandemic.

Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test-and-treat program.

Dried blood spots (DBS) are a reliable tool to diagnose viremic hepatitis C virus (HCV) infection. We evaluated the clinical performance of a DBS-based molecular assay for the assessment of cure and reinfection after on-site treatment at a harm reduction center (HRC). Genotyping from DBS samples was also assessed to discriminate reinfection from treatment failure. People who inject drugs (PWID) from an ongoing test-and-treat pilot at the largest HRC in Barcelona were included in the study. HCV-RNA detection from DBS collected after treatment (with follow-up at 12, 36, and 60 weeks) was compared with a molecular point-of-care test using finger-stick blood (GeneXpert). Baseline and follow-up DBS samples were genotyped by NS5B sequencing or commercial real-time PCR. Among treated patients, 193 follow-up DBS samples were tested. The DBS-based assay showed 100% specificity (129/129), and sensitivity ranged from 84.4% to 96.1% according to different viral load cut-offs (from detectable to 3000 IU/mL). Sensitivity as test of cure (follow-up 12) ranged from 85.1% to 97.4%. Among the 64 patients with recurrent viremia, 10.9% had low viral loads (≤1000 IU/mL); HCV genotyping allowed us to classify 73.5% of viremic cases either as reinfection or as treatment failure. DBS samples are useful to assess cure and differentiate reinfection from relapse after HCV antiviral treatment in the real world, facilitating decentralization of treatment and posttreatment follow-up in PWID. However, a fraction of patients presented with low viral loads, limiting viremia detection and genotyping in DBS and, therefore, repeat testing is recommended.

HCV microelimination in harm reduction centres has benefits beyond HCV cure but is hampered by high reinfection rates.

Background & Aims: Significant scale-up of treatment among people who inject drugs (PWID) is crucial to achieve WHO HCV elimination targets. We explored the impact of on-site HCV diagnosis and treatment on PWID in an externalised hepatology clinic at the biggest harm reduction centre (HRC) in Barcelona attending to a marginalised PWID population with ongoing high-risk practices. Methods: On-site HCV point-of-care testing was performed for diagnosis and treatment delivery. HCV-RNA was assessed at SVR12 (sustained virologic response at 12 weeks) and every 6 months. The programme included behavioural questionnaires at baseline and after treatment. Results: Between 2018 and 2020, 919 individuals were prospectively enrolled. Of these, only 46% accepted HCV screening. HCV-RNA+ prevalence was 55.7% (n = 234). Of the 168 (72%) individuals starting treatment, 48% were foreigners, 32% homeless, 73% unemployed, and 62% had a history of incarceration. At enrolment, 70% injected drugs daily and 30% reported sharing needles or paraphernalia. Intention-to-treat SVR12 was 60%; only 4% were virological failures, the remaining were either early reinfections (20%) or losses to follow-up (16%). The overall reinfection rate during follow-up was 31/100 persons/year. HIV coinfection and daily injection were associated with a higher risk of reinfection. Nonetheless, beyond viral clearance, antiviral therapy was associated with a significant reduction in injection frequency, risk practices, and homelessness. Conclusions: HCV treatment can be successfully delivered to active PWID with high-risk practices and has a significant benefit beyond HCV elimination. However, approaching this difficult spectrum of the PWID population implies significant barriers such as low rate of screening acceptance and high dropout and reinfection rates. Lay summary: People who inject drugs attending harm reduction centres represent the most difficult population to treat for hepatitis C. We show that hepatitis C treatment has a significant benefit beyond viral cure, including improving quality of life, and decreasing injection frequency and risk practices. However, intrinsic barriers and the high reinfection rates hamper the achievement of viral microelimination in this setting.

Relevancia clínica de la técnica de utilización de inhaladores en pacientes con enfermedad pulmonar obstructiva crónica / The clinical relevance of inhalation technique in chronic obstructive pulmonary disease patients

Introducción:Numerosos estudios muestran que los pacientes con Enfermedad Pulmonar Obstructiva Crónica (EPOC) realizan una técnica de inhalación (TI) incorrecta. Nuestra investigación pretende describir los errores cometidos y la Importancia Clínica de dichos Fallos (ICF), e identificar los factores relacionados con ello.Pacientes y métodos:Estudio descriptivo transversal de 995 pacientes seguidos en 20 Centros de Salud de Andalucía. Se recogieron variables sociodemográficas, calidad de vida, estado mental-cognitivo, espirometría, gravedad, número de dispositivos, realización correcta de la TI, instrucción previa e ICF.Resultados:906 pacientes (91,1%) realizaban una TI incorrecta. Los errores más frecuentes presentaban ICF2-moderada y se relacionaron con nivel cognitivo bajo, pico flujo inhalatorio bajo y menos visitas al neumólogo. Los errores críticos-ICF3 mostraron relación con mayor gravedad, uso de Turbuhaler® y peor calidad de vida.Discusión:Altísima tasa de técnica incorrecta cuyos errores más frecuentes comprometen de forma moderada la eficacia del fármaco, se relacionan con el modo de realizar la TI y no con la dificultad en el manejo del dispositivo. Esto muestra la importancia de entrenar correctamente a nuestros pacientes. (AU)

Introduction:Numerous studies show that patients with chronic obstructive pulmonary disease (COPD) perform an incorrect inhalation technique (IT). This research aims to describe inhalation errors committed and their clinical importance, and to identify factors related to them.Patients and methods:A total of 995 patients were recruited in this cross-sectional, descriptive study that was conducted across 20 Andalusian Health Care Centres. The following variables were collected: socio-demographic data, quality of life, mental and cognitive status, spirometry tests, severity, number of IT devices, IT correct performance, previous instruction and clinical importance of errors.Results:Of the 995 patients, 906 (91,1%) performed an incorrect IT. The most common errors showed moderate errors, which were related to low-cognitive level, low-peak expiratory flow and fewer medical consultations with the pulmonologist. Critical errors were correlated with greater severity, usage of Turbuhaler® and worse quality of life.Discussion:Soaring incorrect technique rate, whose most common errors sparingly compromise the drug effectiveness. These errors are related to the way the patients perform the IT, and not to the difficulty in handling the device. This information demonstrates the relevance of training patients in a proper way. (AU)

Humoral Responses and Ex Vivo IFN-γ Production after Canine Whole Blood Stimulation with Leishmania infantum Antigen or KMP11 Recombinant Protein.

The effect of Leishmania infantum soluble antigen (LSA) and recombinant Kinetoplastid Membrane Protein 11 (rKMP11) on the induction of ex vivo specific IFN-γ (n = 69) and antibody responses (n = 108) was determined in dogs. All dogs were tested for serological response to both antigens and divided into Group 1: healthy (Asturias, Spain, n = 26), Group 2: sick (n = 46), Group 3: healthy Ibizan hounds (Mallorca, Spain, n = 22) and Group 4: healthy (Bari, Italy, n = 14). Antibody levels were higher for LSA when compared to rKMP11 (p = 0.001). Ibizan hounds were all seronegative to rKMP11 and 18% were low seropositive to LSA. Sick dogs presented higher antibody response to both antigens compared to the rest of the groups (p < 0.0001). All groups showed higher IFN-γ levels after LSA compared to rKMP11 responses (p < 0.05). The highest response to LSA was found in Ibizan hounds (p < 0.05). IFN-γ to LSA and rKMP11 stimulation was observed in 34% and in 2.8% of the sick dogs, respectively. Here, we demonstrated that anti-rKMP11 antibodies are mainly present in dogs with moderate to severe disease. Furthermore, cellular immune response measured by specific ex vivo IFN-γ production was more intense to LSA than stimulated to rKMP11.

[The clinical relevance of inhalation technique in chronic obstructive pulmonary disease patients]. / Relevancia clínica de la técnica de utilización de inhaladores en pacientes con enfermedad pulmonar obstructiva crónica.

INTRODUCTION: Numerous studies show that patients with chronic obstructive pulmonary disease (COPD) perform an incorrect inhalation technique (IT). This research aims to describe inhalation errors committed and their clinical importance, and to identify factors related to them. PATIENTS AND METHODS: A total of 995 patients were recruited in this cross-sectional, descriptive study that was conducted across 20 Andalusian Health Care Centres. The following variables were collected: socio-demographic data, quality of life, mental and cognitive status, spirometry tests, severity, number of IT devices, IT correct performance, previous instruction and clinical importance of errors. RESULTS: Of the 995 patients, 906 (91,1%) performed an incorrect IT. The most common errors showed moderate errors, which were related to low-cognitive level, low-peak expiratory flow and fewer medical consultations with the pulmonologist. Critical errors were correlated with greater severity, usage of Turbuhaler® and worse quality of life. DISCUSSION: Soaring incorrect technique rate, whose most common errors sparingly compromise the drug effectiveness. These errors are related to the way the patients perform the IT, and not to the difficulty in handling the device. This information demonstrates the relevance of training patients in a proper way.

Neurodegenerative Diseases: A Multidisciplinary Approach.

The rapid pattern of population ageing in recent years increases the risk of appearance of associated neurodegenerative diseases. Dementias are one of the most feared disorders, and although not necessarily all elderly people have dementia, the number of people with this disease is increasing rapidly. The causes of dementia are multiple, and the diagnosis of the different types of dementia is complicated since most patients display mixed dementias and symptoms overlapping. Personalized diagnosis and treatments would be desirable, but this requires a deep knowledge of each type of dementia where a multidisciplinary approach would be ideal. Thus, the aim of this review is to summarize the features of the main types of dementia as well as to compilate the more recent findings on this subject, ranging from genetic and molecular studies to animal models, including the use of omics platforms based on powerful hybrid instrumental techniques, and neuroimage techniques. On the other hand, we consider the aspects that can prevent these disorders and depend on modifiable factors, such as diet, among others. Finally, new technologies, such as nanotechnology can provide novel strategies for the administration of effective treatments. In this regard, our purpose is to provide the most updated and complete overview of state of the art about characteristics of these disorders.

Subarachnoid hemorrhage due to intradural cerebral aneurysm and simultaneous spinal subdural hematoma: illustrative case.

BACKGROUND: Spontaneous spinal subdural hematomas (SSDHs) are unusual. Among their probable etiologies, an association with ruptured brain aneurysms has been described in an extraordinary way. The underlying pathophysiological mechanism is not conclusively described in the literature. OBSERVATIONS: The authors reported an exceptional case of a 59-year-old woman admitted for a condition that included sudden headache, stiff neck, and vomiting associated with pain in the left flank area that radiated to the leg. Computed tomography (CT) of the brain evidenced acute subarachnoid hemorrhage distributed in the bilateral posterior parieto-occipital fossa and occipital horns of the ventricles. CT angiography detected a dissecting aneurysm in the left vertebral artery (V4) that was treated urgently via the endovascular route. In the next hours, the patient's symptoms worsened, with paraplegia of the lower extremities. Magnetic resonance imaging showed SSDH at T4-6 and extensive associated myelopathy. LESSONS: The origin of the spinal hematoma may be the rupture of the aneurysm of the V4 segment in the dura mater of the foramen magnum and subsequent rostrocaudal migration of the hemorrhage to the spinal subdural space, enhanced by an intracranial pressure increase. This hypothesis is discussed, as is a brief literature review.

Genetic similarities versus morphological resemblance: Unraveling a polyploid complex in a Mediterranean biodiversity hotspot.

The Balkan Peninsula is recognized as one of the hotspots of biodiversity in Europe. This area has shown since the Last Glacial Maximum appropriate conditions for species diversification and hybridization, which has led to the existence of numerous taxonomically unresolved entities. Here, we focus on the Western Balkans and explore the genetic structure and relationships among species belonging to the V. austriaca - V. orbiculata diploid-polyploid complex, including populations showing intermediate morphologies. A combination of nuclear markers (microsatellites), plastid DNA regions (trnH-psbA, ycf6-psbM) and ploidy level estimations using flow cytometry are employed to assess the genetic structure and evolutionary dynamics of this polyploid complex. To reconstruct the evolutionary history, an approximate Bayesian computation approach is combined with projections of the species distribution models onto the climatic scenarios of the Mid-Holocene (6 ka BP) and Last Glacial Maximum (22 ka BP). Four main groups were found: one well-established entity within the diploid level, V. dalmatica, a second diploid-tetraploid group which corresponds to V. orbiculata, a hexaploid cluster harboring V. austriaca subsp. jacquinii individuals, and an enigmatic tetraploid group. According to the molecular data obtained, this latter cluster represents an allopolyploid cryptic lineage −with V. orbiculata and V. dalmatica as putative parents− morphologically similar to V. orbiculata, but genetically more related to V. austriaca subsp. jacquinii. Veronica dalmatica and this "uncertain tetraploid" group are involved in the formation of the hexaploid taxon V. austriaca subsp. jacquinii, with the possibility of recent gene flow among different cytotypes. The present study supports a scenario of diversification from a diploid common ancestor leading to two different but interrelated lineages. The first one would correspond with the diploid V. orbiculata plus tetraploid individuals of this species arising through allo- and autopolyploidization, and the second one would involve all ploidy levels with allopolyploidization being prevalent.

Glycemic variability: prognostic impact on acute ischemic stroke and the impact of corrective treatment for hyperglycemia. The GLIAS-III translational study.

INTRODUCTION: Glycemic variability (GV) represents the amplitude of oscillations in glucose levels over time and is associated with higher mortality in critically ill patients. Our aim is to evaluate the impact of GV on acute ischemic stroke (IS) outcomes in humans and explore the impact of two different insulin administration routes on GV in an animal model. METHODS: This translational study consists of two studies conducted in parallel: The first study is an observational, multicenter, prospective clinical study in which 340 patients with acute IS will be subcutaneously implanted a sensor to continuously monitor blood glucose levels for 96 h. The second study is a basic experimental study using an animal model (rats) with permanent occlusion of the middle cerebral artery and induced hyperglycemia (through an intraperitoneal injection of nicotinamide and streptozotocin). The animal study will include the following 6 groups (10 animals per group): sham; hyperglycemia without IS; IS without hyperglycemia; IS and hyperglycemia without treatment; IS and hyperglycemia and intravenous insulin; and IS and hyperglycemia and subcutaneous insulin. The endpoint for the first study is mortality at 3 months, while the endpoints for the animal model study are GV, functional recovery and biomarkers. DISCUSSION: The GLIAS-III study will be the first translational approach analyzing the prognostic influence of GV, evaluated by the use of subcutaneous glucose monitors, in acute stroke. Trial registration https://www.clinicaltrials.gov (NCT04001049).

Environmental differences are correlated with the distribution pattern of cytotypes in Veronica subsection Pentasepalae at a broad scale.

BACKGROUND AND AIMS: The distribution of cytotypes and its potential correlation with environmental variables represent a cornerstone to understanding the origin and maintenance of polyploid lineages. Although many studies have addressed this question in single species at a regional scale, only a few have attempted to decipher this enigma in groups of closely related species at a broad intercontinental geographical scale. Here, we consider approx. 20 species of a diploid-polyploid complex (Veronica subsect. Pentasepalae) of recent and rapid diversification represented in Europe and North Africa to study the frequency and distribution of cytotypes and their relationship to environmental variables. METHODS: A total of 680 individuals (207 populations) were sampled. Ploidy levels were determined using flow cytometry. Ecological differentiation among cytotypes was tested using climatic and environmental variables related to temperature, precipitation, vegetation and biogeographical region, among others, and by performing univariate and multivariate (constrained principal coordinates analysis) analyses. KEY RESULTS: Four ploidy levels (2x, 4x, 6x and 8x) were found and genome downsizing was observed to occur within the group. Plants of different ploidy level are ecologically differentiated, with hexaploids and octoploids occurring in wetter and colder habitats with a higher seasonality than diploids. A south to north distribution pattern was found, with diploids occupying southern refugial areas and octoploids being more frequent in northern regions of Europe above the permafrost boundary. CONCLUSIONS: The distribution of cytotypes can be explained by ecological differentiation, the geographical position of refuge areas during the Quaternary climatic oscillations as well as by ice and permafrost retreat patterns. The Balkan Peninsula constitutes the most important contact zone between cytotypes. This work provides the first comprehensive ploidy screening within V. subsect. Pentasepalae at a broad scale and indicates that polyploidy and genome downsizing might have contributed to the colonization of new habitats in a recently diverged polyploid complex.

Utility of a one-step screening and diagnosis strategy for viremic HCV infection among people who inject drugs in Catalonia.

BACKGROUND: In Catalonia (Spain), people who inject drugs (PWID) face numerous barriers to access to mainstream healthcare services for hepatitis C confirmatory diagnosis and treatment, so simplified testing strategies for viremic infection are urgently needed. Among PWID attending harm-reduction services in Catalonia, we aimed (i) to assess the utility of an in-house HCV-RNA detection assay on dried blood spots (DBS) as a one-step screening and confirmatory diagnosis strategy for hepatitis C, (ii) to estimate the prevalence of viremic HCV infection, and (iii) to identify factors associated with unawareness of viremic infection. METHODS: A cross-sectional study of current PWID (N â€¯= 410) was performed in four harm-reduction services. All participants underwent HCV antibody point-of-care testing and parallel DBS collection for centralized RNA testing. An epidemiological questionnaire was administered. Paired EDTA-plasma samples were additionally collected for HCV viral load testing in 300 participants. RESULTS: HCV-RNA testing from DBS was feasible and showed 97.2% sensitivity and 100% specificity for viral loads >3000 IU/mL in real-life conditions. No significant differences in the performance when detecting viremic infections were observed between this one-step testing strategy vs. the conventional two-step algorithm involving venepuncture. Overall HCV seroprevalence was 79.8%, and prevalence of viremic infection was 58.5%. Importantly, 35.8% of viremic HCV participants were unaware of their status, and no specific socio-demographic or bio-behavioral factors independently associated with unawareness of viremic infection were identified. Among participants reporting a past or current HCV infection, 29.0% stated having received HCV antiviral treatment. CONCLUSION: The high viremic HCV infection burden among PWID attending HRS, estimated for the first time in Catalonia, together with the low levels of awareness of viremic status and access to treatment, suggest that scaling up this one-step screening and diagnosis strategy to the network of harm-reduction services would help to achieve HCV elimination targets set by the World Health Organization.

Cytokine Effect of TLR3, TLR4, and TLR7 Agonists Alone or Associated with Leishmania infantum Antigen on Blood from Dogs.

Activation of toll-like receptors (TLRs) has been shown to play an important role in leishmaniosis by enhancing the parasite specific immune responses to control infection. However, the role of TLR agonists has not been studied in detail in dogs. The aim of this study was to determine the effect of TLR3, TLR4, and TLR7 agonists (TLR3a, TLR4a, and TLR7a) alone or in combination with Leishmania infantum antigen (LSA) on TNF-α and IL-6 production in blood from dogs living in endemic areas of canine leishmaniosis (CanL). Twenty-four healthy dogs from Catalonia (n=14) and Ibizan hound dogs from the island of Mallorca (n=10) were enrolled. Whole blood with TLR3a, TLR4a, and TLR7a alone or combined with LSA were cultured separately, and IFN-γ, TNF-α, and IL-6 were measured by ELISA. A significant increase of TNF-α was found for all conditions studied compared to medium alone. Stimulation with TLR4a (p=0.0001) and TLR7a (p=0.005) presented a significantly marked increase in TNF-α and IL-6 production compared to TLR3a. Importantly, significantly higher TNF-α production was found in LSA+TLR4a (p=0.0001) stimulated blood and LSA+TLR7a (p=0.005) compared to LSA alone. All dogs showed higher TNF-α production after LSA+TLR7a compared to TLR7a (p=0.047) and LSA+TLR3a compared to TLR3a (p=0.052). These data indicate a marked inflammatory cytokine effect of TLR4a and TLR7a on blood from healthy dogs living in endemic areas of CanL. Additionally, LSA+TLR7a promoted a synergistic proinflammatory effect with TNF-α in all dogs. Those findings suggest an active role of TLRs in proinflammatory responses, which might be strongly involved in the process of disease resolution.

Neuroprotective Natural Molecules, From Food to Brain.

The prevalence of neurodegenerative disorders is increasing; however, an effective neuroprotective treatment is still remaining. Nutrition plays an important role in neuroprotection as recently shown by epidemiological and biochemical studies which identified food components as promising therapeutic agents. Neuroprotection includes mechanisms such as activation of specific receptors, changes in enzymatic neuronal activity, and synthesis and secretion of different bioactive molecules. All these mechanisms are focused on preventing neuronal damage and alleviating the consequences of massive cell loss. Some neuropathological disorders selectively affect to particular neuronal populations, thus is important to know their neurochemical and anatomical properties in order to design effective therapies. Although the design of such treatments would be specific to neuronal groups sensible to damage, the effect would have an impact in the whole nervous system. The difficult overcoming of the blood brain barrier has hampered the development of efficient therapies for prevention or protection. This structure is a physical, enzymatic, and influx barrier that efficiently protects the brain from exogenous molecules. Therefore, the development of new strategies, like nanocarriers, that help to promote the access of neuroprotective molecules to the brain, is needed for providing more effective therapies for the disorders of the central nervous system (CNS). In order both to trace the success of these nanoplatforms on the release of the bioactive cargo in the CNS and determinate the concentration at trace levels of targets biomolecules by analytical chemistry and concretely separation instrumental techniques, constitute an essential tool. Currently, these techniques are used for the determination and identification of natural neuroprotective molecules in complex matrixes at different concentration levels. Separation techniques such as chromatography and capillary electrophoresis (CE), using optical and/or mass spectrometry (MS) detectors, provide multiples combinations for the quantitative and qualitative analysis at basal levels or higher concentrations of bioactive analytes in biological samples. Bearing this in mind, the development of food neuroprotective molecules as brain therapeutic agents is a complex task that requires the intimate collaboration and engagement of different disciplines for a successful outcome. In this sense, this work reviews the new advances achieved in the area toward a better understanding of the current state of the art and highlights promising approaches for brain neuroprotection.

Phylogeography of an endangered disjunct herb: long-distance dispersal, refugia and colonization routes.

Quaternary glacial cycles appear to have had a consistent role in shaping the genetic diversity and structure of plant species. Despite the unusual combination of the characteristics of the western Mediterranean-Macaronesian area, there are no studies that have specifically examined the effects of palaeoclimatic and palaeogeographic factors on the genetic composition and structure of annual herbs. Astragalus edulis is a disjunct endemic found in the easternmost Canary Islands and the semi-arid areas of north-eastern Africa and south-eastern Iberian Peninsula. This endangered species shows no evident adaptations to long-distance dispersal. Amplified fragment length polymorphism (AFLP) data and plastid DNA sequences were analysed from a total of 360 individuals distributed throughout the range of this species. The modelled potential distribution of A. edulis under current conditions was projected over the climatic conditions of the Last Interglacial (130 ka BP) and Last Glacial Maximum (21 ka BP) to analyse changes in habitat suitability and to look for associations between the modelling and genetic results. Amplified fragment length polymorphism analysis showed clear phylogeographic structure with four distinct genetic clusters. Approximate Bayesian computation (ABC) models based on plastid DNA sequences indicated a Middle Pleistocene long-distance dispersal event as the origin of the populations of the Canary Islands. The models also suggested south-western Morocco as the ancestral area for the species, as well as subsequent colonization of north-eastern Morocco and the Iberian Peninsula. The data compiled indicated the possibility of the presence of refuge areas at favourable locations around the High Atlas and Anti-Atlas mountain ranges. Moreover, palaeodistribution models strongly support the events inferred by ABC modelling and show the potential distribution of the species in the past, suggesting a putative colonization route.