Landscape heterogeneity increases the stability of wild ungulate populations facing climatic variability in Mediterranean ecosystems.

Mediterranean environments are characterized by strong intra- and inter-annual fluctuations in plant primary production, which are likely to regulate the carrying capacity and density-dependent responses of ungulate populations. These effects may, however, vary across spatial and temporal scales. Habitat heterogeneity, particularly when associated to differentiated phenological responses, may allow wild ungulates to mitigate temporal fluctuations in plant production by using different resources along the year. In this work, we use a 15-years dataset (including remote-sensing data on vegetation distribution, phenology and production, as well as ungulate population counts) to assess how temporal variability in plant primary production and livestock abundance influence the population dynamics of two wild ungulates: native red deer, Cervus elaphus, and introduced fallow deer, Dama dama. Results show that temporal alternation in the phenological cycles of the four different vegetation types increased plant production, thus food availability for ungulates, within each year. Furthermore, complementarity in the responses of different vegetation types to variations in the amount and timing of rainfall increased the predictability of food availability across different years. This complementarity effect was further increased by the contrasting responses of ungulate populations to variation in the production of different vegetation types. Furthermore, domestic ungulates had positive effects on wild ungulate density at low to intermediate abundances, but high livestock densities decreased ungulate density and constrained the stability of the plant-ungulate system in response to the impact of climatic variation, particularly under climate change. Our findings deepen the knowledge on vegetation-ungulate interactions in Mediterranean areas, potentially contributing to develop better management strategies of ungulate populations and adapt them to ongoing climate change.

Dimensional study of prostate cancer using stereological tools.

This study analyzes the dimensional changes of the glands from prostate cancer by applying stereology to estimate the variations in volume, length, surface, and cellular densities of tumor acini. Normal and tumor acini were visualized using immunohistochemistry for cytokeratin18. On immunostained sections, parameters related to the dimensions and cell population of prostate acini were measured. The immunohistochemical expression of proliferative cell nuclear antigen was also measured to correlate the quantitative changes estimated with the proliferative activity of the epithelium. The average cell volume in normal and tumor epithelium was estimated using the method of the nucleator. The relative size of the acini was similar in the carcinoma compared with the normal prostate. Within the acini, the fraction of acinar volume occupied by the epithelium was significantly higher in cancer than in the nontumor prostate. Conversely, the glandular lumen of the cancer acini is lower than in the normal acini. The significant increase of acinar length density in the carcinoma indicates that the glandular tree's growth in the carcinoma is higher and with more branches than in the case of nonneoplastic glands. The basal surface density is higher in the carcinoma than in the controls. The number of epithelial cells per unit length of acini was significantly decreased in the neoplastic glands. This "dilution" of the cell population along the cancer acinus can be explained by the significant increase in the tumor cell's mean cell volume.

Valproic acid during pregnancy decrease the number of spermatogenic cells and testicular volume in the offspring of mice: Stereological quantification.

Valproic acid (VPA) is a drug used to treat epilepsy, bipolar disorders and headaches. As a secondary effect, this antiepileptic drug can cause a decrease in androgens and gonadotropins, and dose-dependent testicular defects, such as reduction of testicular weights, sperm motility and degeneration of the seminiferous tubules. In offspring exposed to VPA, its effects have not been evaluated, so the study aimed to determine the morphological effects of the use of VPA along testicular development in mice. 30 adult female BALB/c mice were crossed and divided by age, with embryos of 12.5 days post coitum (dpc), fetuses of 17.5 dpc and male mice 6 weeks postnatal. In each case, the pregnant mouse received 600 mg/kg of VPA, making up the VPA groups, or 0.3 mL of 0.9% physiological solution for the control groups, from the beginning to the end of the pregnancy, orally.t. A morpho-quantitative analysis was carried out on the gonadal development of the male offspring. In the groups treated with VPA, at all ages studied they had lower testicular volume. At 12.5 dpc, they showed less testicular development in the form of sex cords, with fewer gonocytes and somatic cells. At 17.5 dpc, they presented greater interstitial space, fewer spermatogonial, sustentacular Sertoli, peritubular and interstitial Leydig cells. At 6 weeks postnatal, they presented fewer spermatogonia, pachytene spermatocytes, elongated spermatids, sustentacular Sertoli and interstitial Leydig cells, with statistically significant differences. In conclusion, prenatal exposure to VPA causes histopathological alterations in the offspring of mice in testicular development, from the embryonic stage to 6 weeks postnatal.

Effects of vitamin e on the epithelial-mesenchymal transition in testicular development exposed to valproic acid / Efectos de la vitamina e en la interacción epitelio-mesenquimático en el desarrollo testicular expuesto a ácido valproico

SUMMARY: In testicular differentiation, somatic cells must adopt a specific destiny towards sustentacular, peritubular and interstitial cells, being fundamental for the morphogenesis of seminiferous tubules, mediated by morphogens such as Desert Hedgehog (DHH), insulin-like growth factor-1 (IGF-1) and fibroblastic growth factor 2 (FGF-2). Its alteration could be related to failures in the development mechanisms, such as those caused by valproic acid (VPA), which can be reversed with vitamin E (VE). The objective of the study was to evaluate the epithelial-mesenchymal transition (EMT) in the testicular development of mice exposed to VPA and VE. 12 groups of pregnant female mice were formed that were separated by days post-coital (dpc) at 12.5 dpc, 17.5 dpc and 6 weeks postnatal, each one subdivided into 4 groups of 5 pregnant women each. Subgroups received different treatments from the beginning to the end of gestation orally: 600 mg/kg of VPA, 600 mg/kg of VPA and 200 IU of VE, 200 IU of VE and the control group 0.3 mL of 0.9% physiological solution. Immunohistochemistry was performed for the detection of DHH, IGF-1 and FGF-2. Immunolocalization of DHH was observed in all stages, with more evident significant differences in integrated optical density (IOD) and percentage of immunoreaction area at 6 weeks postnatal, being lower in the VPA group. In IGF-1, lower intensity and distribution of immunostaining was observed in the fetal and pubertal stages in the VPA groups, a similar situation with FGF-2, but only evident at 17.5 dpc, with significant differences. These results demonstrate that VPA can alter EMT between somatic cells in testicular development, with VE being an agent capable of attenuating this process.

RESUMEN: En la diferenciación testicular, es necesario que las células somáticas adopten un destino específico hacia células sustentaculares, peritubulares e intersticiales, siendo fundamental para la morfogénesis de los túbulos seminíferos, mediado por morfógenos como Desert Hedgehog (DHH), Factor de Crecimiento Fibroblástico 2 (FGF-2) y Factor de Crecimiento símil a Insulina (IGF-1). Su alteración se podría relacionar a fallas en los mecanismos de desarrollo, como los que ocasiona el ácido valproico (VPA), los cuales pueden ser revertidos con la vitamina E (VE). El objetivo de estudio fue evaluar la transición epitelio-mesenquimática (EMT) en el desarrollo testicular de ratones expuestos a VPA y VE. Se conformaron 12 grupos de ratones hembra gestantes que se separaron por días post-coital (dpc) a los 12.5 dpc, 17.5 dpc y 6 semanas post-natal, cada uno subdividido en 4 grupos de 5 gestantes cada uno. Cada subgrupo recibió diferentes tratamientos desde el inicio hasta el término de la gestación vía oral: 600 mg/kg de VPA, 600 mg/kg de VPA y 200 UI de VE, 200 UI de VE y el grupo control 0,3 mL de solución fisiológica 0,9%. Se realizó técnica inmunohistoquímica para la detección de DHH, IGF-1 y FGF-2. Se observó la inmunolocalización de DHH en todos los estadios, con diferencias significativas más evidentes en la densidad óptica integrada (IOD) y porcentaje de área de inmunoreacción a las 6 semanas post-natal, siendo menor en el grupo VPA. En IGF-1, se observó en la etapa fetal y puberal menor intensidad y distribución de la marcación en los grupos VPA, situación similar con la inmunomarcación de FGF-2, pero sólo evidenciándose a los 17.5 dpc, con diferencias significativas. Estos resultados demuestran que el VPA puede alterar la EMT entre las células somáticas en el desarrollo testicular, siendo la VE un agente capaz de atenuar este proceso.

Protective role of vitamin E in testicular development of mice exposed to valproic acid.

Valproic acid (VPA) is a teratogenic antiepileptic, causing alterations in oxidative stress in prenatal development, being altered the development of the male reproductive system. The purpose of this study was to determine the protective effect of vitamin E (VE) on the testicular development in embryos, foetuses and pubertal mice exposed to VPA, VPA+VE and only VE. Sixty pregnant adult female mice were used, to which they were administered 600 mg/kg of VPA (VPA groups), 600 mg/kg of VPA and 200 IU of VE (VPA+VE groups), 200 IU VE (VE groups) and 0.3 ml of 0.9% physiological solution (control groups), showing at 12.5 days post-coital (dpc), 17.5 dpc and 6 weeks postnatal testicular development, and proliferative and apoptotic indices. The groups treated with VPA presented a smaller testicular volume, with greater interstitial space and a delay in the conformation of the testicular cords, shorter lengths and diameters of the germinal epithelium, a smaller number of germline and somatic cells, an increase in cells apoptotic and less proliferation, with significant differences. VE-treated groups behaved similarly to controls. In conclusion, VE reduces the effects caused by VPA throughout testicular development, from embryonic stages, continuing until pubertal stages.

[Hypersensitivity to ß-lactam antibiotics: algorithms of management and desensitization as a vital therapeutic alternative]. / Hipersensibilidad a antibióticos betalactámicos: algoritmos de manejo y desensibilización como alternativa terapéutica vital.

Hypersensitivity reactions can be complex and life-threatening to patients, especially when drugs such as ß-lactam antibiotics are involved. To this day, there are diagnostic algorithms and mobile applications that improve the clinical approach, as well as laboratory tests and more specialized procedures, such as skin tests and controlled exposure tests; which are useful for identifying the drug involved and for selecting safe and effective therapeutic alternatives. For several years, the desensitization procedure has been positioned as a vital tool for clinical allergists and for their patients, and it is key to improving clinical outcomes such as survival and quality of life.

Las reacciones de hipersensibilidad pueden ser complejas y poner en peligro la vida de los pacientes, más cuando se involucran medicamentos como los antibióticos betalactámicos. A la fecha, se dispone de algoritmos diagnósticos y aplicaciones móviles que facilitan el abordaje clínico, así como pruebas de laboratorio y procedimientos más especializados, como las pruebas cutáneas y de exposición controlada, útiles para la identificación de la sustancia implicada y para la selección de alternativas terapéuticas seguras y efectivas. Desde hace varios años, el procedimiento de desensibilización se ha posicionado como una herramienta vital para el alergólogo clínico y los pacientes, y es clave para mejorar los desenlaces clínicos, tanto la supervivencia como la calidad de vida.

IgE, blood eosinophils and FeNO are not enough for choosing a monoclonal therapy among the approved options in patients with type 2 severe asthma.

Type-2 inflammation is the most frequent endophenotype of asthma. Different biomarkers have been proposed to identify this inflammation because highly effective therapies have improved type-2 severe asthma control. We investigated the frequency of some biomarkers of type-2 inflammation (total IgE, sIgE, blood eosinophil, and FeNO) in the framework of severe asthma and assessed its ability to help us to choose the best biological therapy for each patient. Different scenarios (sensitivity analysis) were evaluated according to the biomarkers proposed for each biological therapy in 72 patients with type-2 severe asthma. Between 54.1% and 68% of patients could receive at least 2 different biological therapies and 34.7%-40.2% could receive any of the 3 types of therapies (anti-IgE, anti-eosinophil, anti-IL4). Biomarkers help to identify type-2 severe asthma but total IgE, sIgE, blood eosinophil, and FeNO are not enough to select 1 specific therapy. With the increasing arrival of new biological therapies, it is necessary to identify new biomarkers that allow us to improve our selection criteria for the best therapy for each patient or to construct a prediction rule.

COVID-19 effective reproduction number dropped during Spain's nationwide dropdown, then spiked at lower-incidence regions.

COVID-19 pandemic has rapidly spread worldwide. Spain has suffered one of the largest nationwide bursts, particularly in the highly populated areas of Madrid and Barcelona (two of the five largest conurbations in Europe). We used segmented regression analyses to identify shifts in the evolution of the effective reproduction number (Rt) reported for 16 Spanish administrative regions. We associate these breaking points with a timeline of key containment measures taken by national and regional governments, applying time lags for the time from contagion to case detection, with their associated errors. Results show an early decrease of Rt that preceded the nationwide lockdown; a generalized, sharp decrease in Rt associated with such lockdown; a low impact of the strengthened lockdown, with a flattening of Rt evolution in high-incidence regions, and even increases in Rt at low-incidence regions; and an increase in Rt associated to the relaxation of the lockdown measures in ten regions. These results evidence the importance of generalized lockdown measures to contain COVID-19 spread, and the limited effect of the subsequent application of a stricter lockdown (restrictions to all non-essential economic activities). Most importantly, they highlight the importance of maintaining strong social distancing measures and strengthening public health control during lockdown de-escalation.

Reporte de caso: Manejo anestésico en un paciente pediátrico con ictiosis más deshidratación grave / Case report: Anesthetic management of an infant patient with ichthyosis plus severe dehydration

INTRODUCTION: Ichthyosis are hereditary disorders of keratinization which are characterized for the presence of hyperkeratosis and/or peeling. This disorder group can put in danger the life of the patient because of the severe alteration of the skin barrier, associated with a severe transdermic loss of water, different grades of hypothermia and a hypernatremic dehydration. OBJECTIVE: Introducing the clinic case of an infant patient with the diagnosis of ichthyosis plus severe dehydration who is scheduled for placement of CVC. CLINICAL CASE: Male infant, 3 months old, with the diagnosis of ichthyosis and severe dehydration, scheduled for placement of CVC. CONCLUSIONS: Due to the urgency of our patient, who presented severe dehydration, an inhaled general anesthesia with sevoflurane and oxygen was decided, without instrumenting the airway which in these patients has the risk of being potentially difficult, from the placement of the face mask itself, until finding lesions within the oral cavity, ventilatory assis- tance should be maintained by the pediatric anesthesiologist, once venous access is achieved, the fluids restitution is performed with loads of 10 to 20 ml/kg of the patient's weight, hyperthermia was controlled with physical means.

INTRODUCCIÓN: Las ictiosis son trastornos hereditarios de la queratinización caracterizadas por la presencia de hiperqueratosis y/o descamación. Este grupo de patologías pueden poner en peligro la vida del paciente debido a la severa alteración de la barrera cutánea, asociada a intensa pérdida transepidérmica de agua, diferentes grados de hipotermia y la deshidratación hipernatrémica. OBJETIVO: Presentar un caso clínico de paciente lactante menor con diagnóstico de ictiosis, cursando un cuadro grave por deshidratación, al que se le instala un CVC. CASO CLÍNICO: Lactante masculino, 3 meses de edad, con diagnóstico de ictiosis y deshidratación grave programado para colocación de CVC. CONCLUSIONES: Debido a la urgencia del paciente quien presentaba un caso de deshidratación severa se decide anestesia general inhalada con sevoflurano y oxígeno, sin instrumentación de la vía área, la cual en estos pacientes tiene el riesgo de ser potencialmente difícil, desde la propia colocación de la mascarilla facial hasta encontrar lesiones dentro de la cavidad oral; se debe mantener la asistencia ventilatoria por el anestesiólogo pediatra, una vez logrado el acceso venoso se procede a la restitución hídrica con cargas de 10 a 20 ml/kg de peso del paciente, el control de la hipertermia fue con medios físicos.

Chasing the ghost of infection past: identifying thresholds of change during the COVID-19 infection in Spain.

One of the largest nationwide bursts of the first COVID-19 outbreak occurred in Spain, where infection expanded in densely populated areas through March 2020. We analyse the cumulative growth curves of reported cases and deaths in all Spain and two highly populated regions, Madrid and Catalonia, identifying changes and sudden shifts in their exponential growth rate through segmented Poisson regressions. We associate these breakpoints with a timeline of key events and containment measures, and data on policy stringency and citizen mobility. Results were largely consistent for infections and deaths in all territories, showing four major shifts involving 19-71% reductions in growth rates originating from infections before 3 March and on 5-8, 10-12 and 14-18 March, but no identifiable effect of the strengthened lockdown of 29-30 March. Changes in stringency and mobility were only associated to the latter two shifts, evidencing an early deceleration in COVID-19 spread associated to personal hygiene and social distancing recommendations, followed by a stronger decrease when lockdown was enforced, leading to the contention of the outbreak by mid-April. This highlights the importance of combining public health communication strategies and hard confinement measures to contain epidemics.

Nasal specific IgE to Der p is not an acceptable screening test to predict the outcome of the nasal challenge test in patients with non-allergic rhinitis.

OBJECTIVES: Nasal specific IgE (NsIgE) is the most common marker to identify type-2 inflammation in local allergic rhinitis (LAR). However, the comparison of NsIgE in different types of rhinitis, its frequency in tropical countries, and its diagnostic performance for predicting the outcome of a nasal challenge test (NCT) has had limited study. The main objective of this study was to explore the diagnostic performance of NsIgE to Dermatophagoides pteronyssinus (Der p) among different types of rhinitis and control subjects in a tropical population. METHODS: We evaluated the frequency of NsIgE, systemic atopy (serum sIgE and Skin Prick Test), and nasal eosinophils, and we performed nasal challenge tests (NCTs) with Der p in 3 groups of patients; rhinitis without atopy (RWoA) (n = 25), rhinitis with atopy (RWA) (n = 25), and control subjects (n = 18). RESULTS: NsIgE had a low sensitivity and specificity to predict a positive NCT in the RWoA group: 48% had NsIgE, but only 28% had a positive NCT. Among the RWA group 84% had NsIgE and 80% had a positive NCT; the association of NsIgE and positive NCT was high (>80%). In the control group 27.8% had NsIgE, but none had a positive NCT. CONCLUSIONS: NsIgE performs poorly in predicting NCT results in patients with non-allergic rhinitis. More methodical investigations are needed in this complex area of rhinitis. In patients with allergic rhinitis, NsIgE was useful in predicting a positive nasal challenge, but not superior to the systemic atopic test.

Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium.

BACKGROUND: The epicardium is the outer mesothelial layer of the heart. It encloses the myocardium and plays key roles in heart development and regeneration. It derives from the proepicardium (PE), cell clusters that appear in the dorsal pericardium (DP) close to the atrioventricular canal and the venous pole of the heart, and are released into the pericardial cavity. PE cells are advected around the beating heart until they attach to the myocardium. Bmp and Notch signaling influence PE formation, but it is unclear how both signaling pathways interact during this process in the zebrafish. RESULTS: Here, we show that the developing PE is influenced by Notch signaling derived from the endothelium. Overexpression of the intracellular receptor of notch in the endothelium enhances bmp expression, increases the number of pSmad1/5 positive cells in the DP and PE, and enhances PE formation. On the contrary, pharmacological inhibition of Notch1 impairs PE formation. bmp2b overexpression can rescue loss of PE formation in the presence of a Notch1 inhibitor, but Notch gain-of-function could not recover PE formation in the absence of Bmp signaling. CONCLUSIONS: Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer.

Evaluating tourist profiles and nature-based experiences in Biosphere Reserves using Flickr: Matches and mismatches between online social surveys and photo content analysis.

Monitoring visitor dynamics and their nature-based experiences is an important dimension in the conservation management of protected areas. In the current digital age, the content analysis of social media information is being increasingly used in such a context. However, research testing whether social media content analysis provides similar information to that obtained from stated preference methods is lacking. We aimed to identify differences in the classification of tourist profiles and nature-based experiences, both from online social surveys and photo content analysis. Our approach targeted Flickr's social media users visiting two Biosphere Reserves in Southern Europe: Doñana and Sierra Nevada. We manually classified the main content of Flickr photos considering different categories of tourist profiles and nature-based experiences. Concurrently, we distributed online surveys to Flickr users responsible for those photos and gathered their self-stated classification of tourist profiles and experiences. Finally, we compared the classification results from both content analysis and online surveys using multiple congruence metrics and tests. Overall, we found both matches and mismatches between the results from content analysis and online surveys depending on the categories of tourist profiles and their experiences. "Landscape and species" was the only category with consistent matches between content analysis and online surveys for both tourist profiles and nature-based experiences. We suggest that conclusions based on content analysis or online surveys alone can lead to incomplete information. Instead, the adoption of both content analysis and online surveys should provide complementary perspectives for the monitoring of nature's cultural capital.

Analysis of wt1a reporter line expression levels during proepicardium formation in the zebrafish.

The epicardium is the outer mesothelial layer of the heart. It covers the myocardium and plays important roles in both heart development and regeneration. It is derived from the proepicardium (PE), groups of cells that emerges at early developmental stages from the dorsal pericardial layer (DP) close to the atrio-ventricular canal and the venous pole of the heart-tube. In zebrafish, PE cells extrude apically into the pericardial cavity as a consequence of DP tissue constriction, a process that is dependent on Bmp pathway signaling. Expression of the transcription factor Wilms tumor-1, Wt1, which is a leader of important morphogenetic events such as apoptosis regulation or epithelial-mesenchymal cell transition, is also necessary during PE formation. In this study, we used the zebrafish model to compare intensity level of the wt1a reporter line epi:GFP in PE and its original tissue, the DP. We found that GFP is present at higher intensity level in the PE tissue, and differentially wt1 expression at pericardial tissues could be involved in the PE formation process. Our results reveal that bmp2b overexpression leads to enhanced GFP level both in DP and in PE tissues.

The current state of the knowledge about local allergic rhinitis.

In recent years, a new phenotype of rhinitis has been described; it is characterized by the local production of specific IgE. There isn't any evidence of systemic atopy and it has been called local allergic rhinitis. Understanding the involved physiopathological mechanisms and the behavior of this phenotype translates into the development of strategies and treatments that improve the quality of life of patients with this disease. Below, we present an updated review of the available information regarding this disease and also of the aspects that are yet unresolved.

En los últimos años se ha descrito un nuevo fenotipo de rinitis, caracterizado por la producción local de IgE específica, sin evidencia de atopia sistémica, el cual se ha denominado rinitis alérgica local. Entender los mecanismos fisiopatológicos implicados y el comportamiento de este fenotipo se traducen en el desarrollo de estrategias y tratamientos que mejoran la calidad de vida de los pacientes con esta enfermedad. En este documento se presenta una revisión actualizada de la información disponible relativa a esta enfermedad y de los aspectos pendientes por resolver.

Supplementation with a Carob (Ceratonia siliqua L.) Fruit Extract Attenuates the Cardiometabolic Alterations Associated with Metabolic Syndrome in Mice.

The incidence of metabolic syndrome (MetS) is increasing worldwide which makes necessary the finding of new strategies to treat and/or prevent it. The aim of this study was to analyze the possible beneficial effects of a carob fruit extract (CSAT+®) on the cardiometabolic alterations associated with MetS in mice. 16-week-old C57BL/6J male mice were fed for 26 weeks either with a standard diet (chow) or with a diet rich in fats and sugars (HFHS), supplemented or not with 4.8% of CSAT+®. CSAT+® supplementation reduced blood glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and circulating levels of total cholesterol, low-density lipoprotein (LDL) cholesterol (LDL-c), insulin, and interleukin-6 (IL-6). In adipose tissue and skeletal muscle, CSAT+® prevented MetS-induced insulin resistance, reduced macrophage infiltration and the expression of pro-inflammatory markers, and up-regulated the mRNA levels of antioxidant markers. Supplementation with CSAT+® prevented MetS-induced hypertension and decreased the vascular response of aortic rings to angiotensin II (AngII). Moreover, treatment with CSAT+® attenuated endothelial dysfunction and increased vascular sensitivity to insulin. In the heart, CSAT+® supplementation reduced cardiomyocyte apoptosis and prevented ischemia-reperfusion-induced decrease in cardiac contractility. The beneficial effects at the cardiovascular level were associated with a lower expression of pro-inflammatory and pro-oxidant markers in aortic and cardiac tissues.

Continuous variation in herkogamy enhances the reproductive response of Lonicera implexa to spatial variation in pollinator assemblages.

Herkogamy, the spatial separation of sex organs in hermaphroditic plants, has been proposed as a mechanism to reduce self-pollination and the associated processes of inbreeding and gamete wastage. Longitudinal herkogamy is the most frequent type, with two subtypes: approach herkogamy (anthers below the stigma), which is associated with diverse pollinator arrays, and reverse herkogamy (anthers above the stigma), associated with specialized, long-tongued pollinators. By using a herkogamy index that varied continuously from negative (reverse herkogamy) to positive (approach herkogamy) values, we studied the effect of continuous variation in herkogamy on pollinator attraction, selfing capability and plant fitness across three populations of Lonicera implexa differing in the relative abundance of long-tongued vs. short-tongued pollinators. Reverse herkogamy was significantly more frequent in the population where long-tongued pollinators were dominant than in the other two populations. Agreeing with this, the main floral visitors of L. implexa individuals with small and large herkogamy index were, respectively, long-tongued and short-tongued pollinators. Spontaneous selfing was low and increased with increasing herkogamy index (i.e. with approach herkogamy), although most of it occurred when there was close distance between anthers and stigma. Fruit production was unrelated to the herkogamy index in the population with long-tongued pollinators, but it increased with approach herkogamy (higher herkogamy index) in the other two populations. In contrast, seeds of individuals with reverse herkogamy (smaller herkogamy indices) germinated better. In this species, continuous variation in herkogamy might function as a reproductive strategy, as different morphotypes might be favoured by different pollinator assemblages.

The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension.

Portal hypertension is a common complication of liver disease, either acute or chronic. Consequently, in chronic liver disease, such as the hypertensive mesenteric venous pathology, the coexisting inflammatory response is classically characterized by the splanchnic blood circulation. However, a vascular lymphatic pathology is produced simultaneously with the splanchnic arterio-venous impairments. The pathological increase of the mesenteric venous pressure, by mechanotransduction of the venous endothelium hyperpressure, causes an inflammatory response involving the subendothelial mast cells and the lymphatic endothelium of the intestinal villi lacteal. In portal hypertension, the intestinal lymphatic inflammatory response through the development of mesenteric-systemic lymphatic collateral vessels favors the systemic diffusion of substances with a molecular pattern associated with damage and pathogens of intestinal origin. When the chronic hepatic insufficiency worsens the portal hypertensive inflammatory response, the splanchnic lymphatic system transports the hyperplasied intestinal mast cells to the mesenteric lymphatic complex. Then, an acquired immune response regulating a new hepato-intestinal metabolic scenario is activated. Therefore, reduction of the hepatic metabolism would reduce its key centralized functions, such as the metabolic, detoxifying and antioxidant functions which would try to be substituted by their peroxisome activity, among other functions of the mast cells.

[Long-term efficacy of omalizumab in patients with conventional treatment-resistant vernal keratoconjunctivitis]. / Eficacia a largo plazo del omalizumab en pacientes con queratoconjuntivitis vernal resistente a tratamiento convencional.

BACKGROUND: In vernal keratoconjunctivitis, traditional treatments are sometimes insufficient for symptom control; the results with omalizumab are promising in resistant cases. CASE REPORT: 15-year-old female adolescent with vernal keratoconjunctivitis who had received multiple ophthalmic treatments, immunotherapy and systemic steroids with no clinical response. She attended a clinical immunology and allergy department where she was started on omalizumab 225 mg every 2 weeks. After 6 months, she showed a decrease in pruritus and photophobia; two years later, both papillae and Horner-Trantas dots had disappeared. She remained symptom-free, and the use of ophthalmic drugs was therefore reduced. The patient missed omalizumab application on 4 occasions; however, symptoms recurred, and the papillae reappeared, but remitted upon drug re-initiation. CONCLUSION: There is a temporal relationship between omalizumab administration and ocular symptom con-trol, with evidence of relapse upon discontinuation.

Antecedentes: En la queratoconjuntivitis vernal, los tratamientos tradicionales a veces son insuficientes para controlar los síntomas; los resultados con omalizumab son prometedores en los casos resistentes. Reporte de caso: Adolescente de 15 años con queratoconjuntivitis vernal quien había recibido múltiples tratamientos oftálmicos, inmunoterapia y esteroides sistémicos sin respuesta clínica. Acudió a un servicio de inmunología clínica y alergia donde se comenzó tratamiento con 225 mg de omalizumab cada dos semanas. Después de seis meses mostró disminución del prurito y de la fotofobia; dos años más tarde habían desaparecido las papilas y puntos de Horner-Trantas. La paciente permaneció sin síntomas, por lo que redujo el uso de medicamentos oftálmicos. En cuatro ocasiones suspendió la aplicación de omalizumab, sin embargo, los síntomas recurrían y reaparecían las papilas, que remitían al reiniciar el fármaco. Conclusión: En la paciente descrita existió relación temporal entre la administración de omalizumab y el control de los síntomas oculares, con evidencia de recaída después de la interrupción.

Quantification of the heterogeneity of cytokeratin 18 immunoexpression in prostate adenocarcinoma and normal prostate: Global and local features.

There are few studies comparing global versus local changes in spatial patterns in prostate cancer. In this study, stereological tools have been applied to find out if the cytokeratin18 (ck18) immunoexpression shows local changes in cancer compared to normal prostate. To verify if these changes are relevant to ascertain differences between normal (CTR) and cancer (Ca) cases, several parameters were estimated. Volume fraction of epithelium immunostained for ck18 (VV ck18), dispersion index of VV ck18, positional variance of VV ck18, and multiscale entropy analysis (MSE) to measure the tissue heterogeneity. The MSE values showing significant differences between CTR and Ca were employed in a discriminant analysis to determine if MSE was able to classify the cases in CTR and Ca groups. The findings obtained indicate that changes in the expression of ck18 by the cancer prostate are heterogeneous. The increase in local variability of ck18 immunoexpression can be related to the increase in heterogeneity of shape and size of the tumor acini. The asymmetry of distribution of the local values of VV ck18 along the axis of the space series may indicate the existence of anisotropy in the distribution of tumor acini. The increase in scale-dependent entropy for VV ck18 in cancer at the morphological level could be interpreted as the macroscopic expression of the same increase at the molecular level already described. The discriminant analysis shows that the dependence on the resolution for MSE values need to be taken into account to characterize the prostate cancer better.